Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

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"documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:77-85" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 133 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 79 "PDF" => 42 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Differences In Hepatic Expression of Iron, Inflammation and Stress-Related Genes in Patients with Nonalcoholic Steatohepatitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "77" "paginaFinal" => "85" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2171 "Ancho" => 1003 "Tamanyo" => 212446 ] ] "descripcion" => array:1 [ "en" => "Effects of excess iron in patients with NAFLD. Hepatic mRNA expression of: A. Inflammatory markers IL-6, IL-1 p, TNFa, NFkB, STAT3, IL-6R and SOCS3 (p values; IL-6: 0.008, IL-1f): 0.06, TNFa: 0.13, NFkB: 0.02, STAT3: 0.97 IL-6R: 0.29, SOCS3: 0.07). B. Iron regulatory genes HAMP, HJV, FPN1 BMP6 and TMPRSS6 (p values; HAMP: 0.04, HJV: 0.16, FPN1: 0.51, BMP6: 0.47 and TMPRSS6: 0.19), and C. Stress-responsive genes CREBH, HO-1 and HIF-1 a (p values; CREBH: 0.007, HO-1: 0.66 and HIF-1 a: 0.35) in NAFLD + iron patients compared to NAFLD-iron patients. All values are shown as medians and statistical significance (p < 0.05) marked* and p < 0.01 is marked.**" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Priya Handa, Bryan D. Maliken, James E. Nelson, Kelly A. Hennessey, L. Akhila Vemulakonda, Vicki Morgan-Stevenson, Barjinder K. Dhillon, Rohit Gupta, Matthew M. Yeh, Kris V. Kowdley" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Priya" "apellidos" => "Handa" ] 1 => array:2 [ "nombre" => "Bryan D." "apellidos" => "Maliken" ] 2 => array:2 [ "nombre" => "James E." "apellidos" => "Nelson" ] 3 => array:2 [ "nombre" => "Kelly A." "apellidos" => "Hennessey" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Akhila Vemulakonda" ] 5 => array:2 [ "nombre" => "Vicki" "apellidos" => "Morgan-Stevenson" ] 6 => array:2 [ "nombre" => "Barjinder K." "apellidos" => "Dhillon" ] 7 => array:2 [ "nombre" => "Rohit" "apellidos" => "Gupta" ] 8 => array:2 [ "nombre" => "Matthew M." "apellidos" => "Yeh" ] 9 => array:2 [ "nombre" => "Kris V." "apellidos" => "Kowdley" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303643?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303643/v1_201905311015/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S166526811930362X" "issn" => "16652681" "doi" => "10.5604/16652681.1226816" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "70184" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:63-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 87 "formatos" => array:3 [ "EPUB" => 4 "HTML" => 45 "PDF" => 38 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Effects of Interleukin-4 and Interleukin-12b Gene Polymorphisms on Hepatitis B Virus Vaccination" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "63" "paginaFinal" => "70" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eun Youn Roh, Eun Young Song, Jong Hyun Yoon, Sohee Oh, Ju Young Chang, Hyunwoong Park, Soo Hyun Seo, Sue Shin" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Eun" "apellidos" => "Youn Roh" ] 1 => array:2 [ "nombre" => "Eun" "apellidos" => "Young Song" ] 2 => array:2 [ "nombre" => "Jong" "apellidos" => "Hyun Yoon" ] 3 => array:2 [ "nombre" => "Sohee" "apellidos" => "Oh" ] 4 => array:2 [ "nombre" => "Ju" "apellidos" => "Young Chang" ] 5 => array:2 [ "nombre" => "Hyunwoong" "apellidos" => "Park" ] 6 => array:2 [ "nombre" => "Soo" "apellidos" => "Hyun Seo" ] 7 => array:2 [ "nombre" => "Sue" "apellidos" => "Shin" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811930362X?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S166526811930362X/v1_201905311015/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "titulo" => "Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "71" "paginaFinal" => "76" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Seyfettin Köklü, Iftihar Köksal, Ulus Salih Akarca, Ayhan Balkan, Rahmet Güner, Aylin Demirezen, Memduh Sahin, Sila Akhan, Reşat Ozaras, Ramazan Idilman" "autores" => array:10 [ 0 => array:4 [ "nombre" => "Seyfettin" "apellidos" => "Köklü" "email" => array:1 [ 0 => "gskoklu@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Iftihar" "apellidos" => "Köksal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "†" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Ulus" "apellidos" => "Salih Akarca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "‡" "identificador" => "aff3" ] ] ] 3 => array:3 [ "nombre" => "Ayhan" "apellidos" => "Balkan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§" "identificador" => "aff4" ] ] ] 4 => array:3 [ "nombre" => "Rahmet" "apellidos" => "Güner" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "||" "identificador" => "aff5" ] ] ] 5 => array:3 [ "nombre" => "Aylin" "apellidos" => "Demirezen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¶" "identificador" => "aff6" ] ] ] 6 => array:3 [ "nombre" => "Memduh" "apellidos" => "Sahin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff7" ] ] ] 7 => array:3 [ "nombre" => "Sila" "apellidos" => "Akhan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "††" "identificador" => "aff8" ] ] ] 8 => array:3 [ "nombre" => "Reşat" "apellidos" => "Ozaras" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "‡‡" "identificador" => "aff9" ] ] ] 9 => array:3 [ "nombre" => "Ramazan" "apellidos" => "Idilman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§§" "identificador" => "aff10" ] ] ] ] "afiliaciones" => array:10 [ 0 => array:3 [ "entidad" => "Department of Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Infectious Disease, Karadeniz University School of Medicine, Trabzon, Turkey" "etiqueta" => "†" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Gastroenterology, Ege University School of Medicine, Izmir, Turkey" "etiqueta" => "‡" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Department of Gastroenterology, Gaziantep University School of Medicine, Gazianatep, Turkey" "etiqueta" => "§" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "Department of Infectious Diseases and Clinical Microbiology, Yildirim Beyazit University School of Medicine, Ankara, Turkey" "etiqueta" => "||" "identificador" => "aff5" ] 5 => array:3 [ "entidad" => "Department of Gastroenterology, Atatürk Education and Research Hospital, Ankara, Turkey" "etiqueta" => "¶" "identificador" => "aff6" ] 6 => array:3 [ "entidad" => "Department of Gastroenterology, Mersin Government Hospital, Mersin, Turkey" "etiqueta" => "**" "identificador" => "aff7" ] 7 => array:3 [ "entidad" => "Department of Gastroenterology, Kocaeli University School of Medicine, Kocaeli, Turkey" "etiqueta" => "††" "identificador" => "aff8" ] 8 => array:3 [ "entidad" => "Department of Infectious Disease, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey" "etiqueta" => "‡‡" "identificador" => "aff9" ] 9 => array:3 [ "entidad" => "Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey" "etiqueta" => "§§" "identificador" => "aff10" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "textoCompleto" => "IntroductionCurrently, treatment of chronic hepatitis C virus(HCV) infection includes interferon free regimens. Directacting antiviral drugs are taken orally and consists of three major subgroups including protease and polymerase inhibitors, and the multifunctional non-structural protein (NS5A).<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Asunaprevir is a non-structural NS3/4A complex protease inhibitor and daclatasvir is a pangenotypic NS5A inhibitor of HCV replication complex. Combination of asunaprevir and daclatasvir has potent activity against genotype 1b HCV infection.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Daclatasvir plus asunaprevir combination has been first approved for the treatment of genoype 1b subgroup in Japan. Recently, Korea, Taiwan, Canada and Turkey have also approved that dual therapy with similar indications.Phase II and III studies showed potent antiviral affects using daclatasvir and asunaprevir combination in patients infected with HCV genotype 1b.<a class="elsevierStyleCrossRefs" href="#bib0015">3-6</a> In the Japan phase 3 study, SVR24 in Japanese patients were 91% and 84% in cir-rhotics and non-cirrhotics respectively.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a> A recent pooled analysis have reported that SVR12 was 84% in patients with cirrhosis and 85% in patients without cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Preliminary data demonstrated the efficacy and safety of dual therapy even in hard to treat patients including patients with cirrhosis, liver transplantation and chronic renal failure.<a class="elsevierStyleCrossRefs" href="#bib0045">9-11</a> However, efficacy and safety data of daclatasvir and asunaprevir combination therapy is scarce other than Japanese studies.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Herein, we evaluated the antiviral activity and safety of daclatasvir and asunaprevir combination therapy in Turkish patients infected with HCV genotype 1b.Material and MethodsStudy designThe study includes the results of patients enrolled in early access program of BMS in Turkey. Inclusion criteria allowed only the patients who were considered to have a serious or life-threatening condition that was impacting life expectancy within 12 months. Patients having Child B or C cirrhosis, or having liver-transplantation history were not allowed to be enrolled into the program. Request forms filled by healthcare professionals were submitted for both BMS company and health authority approval. All patients signed the informed consent forms before the treatment. The program started at February 2014 and ended in August 2014.TreatmentDual therapy was provided before commercialization in early access program. All patients received daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks unless a viral breakthrough developed. All patients were visited at each 4 week during the treatment period and at the 12th week after treatment. Biochemical tests, complete blood count, coagulation tests and HCV RNA were tested at each visit. HCV RNA was tested once more when it became positive suggesting viral breakthrough or recurrence.<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0005">•HCV RNA assessment. Hepatitis C virus RNA was quantified using the Roche COBAS® TaqMan® assay with an LLOQ of 15 IU/mL.</li><li class="elsevierStyleListItem" id="u0010">•Resistance analysis. Direct sequencing from baseline samples was performed in a group of patients from one center (23 patients). Only NS5A resistance was analysed in that group.</li><li class="elsevierStyleListItem" id="u0015">•Efficacy. Sustained virologic response (SVR12) at post-treatment week 12.</li><li class="elsevierStyleListItem" id="u0020">•Safety assessments. Based on incidence of adverse events (AE), serious adverse events (SAE), discontinuations because of adverse events, and grade 3 or 4 laboratory abnormalities. Adverse events were recorded at each 4-week visit during study follow-up.</li><li class="elsevierStyleListItem" id="u0025">•Cost effectivity. Markov simulation model was used to estimate the cost-effectiveness of dual therapy, and the effectivity was compared with available treatment regimens paid by social security institution in Turkey (pegylated interferon+ribavirin ± telaprevir or bo- ceprevir).</li></ul>Statistical analysisContinuous variables were analyzed using the Mann-Whitney U-test, and categorical variables were analyzed using the paired sample test. All statistical analyses were performed using the SPSS software package (version 16.0 for Windows, SPSS Inc., Chicago, IL, USA), with p < 0.05 denoting statistical significance.ResultsPatient characteristics before daclatasvir plus asunaprevir treatmentFifty-seven patients completed 24 weeks of dual treatment. Two patients died at 12-14th week of treatment as a consequence of miliary tuberculosis in one and systemic vasculitis in the other. Both were HCV RNA negative at week 8 and 12. Ten were treatment-naïve, 15 were in the interferon-ineligible/intolerant group, 14 were relapser and 22 were in the non-responder group (null responders and partial responders).Demographic baseline and laboratory characteristics of patients are shown in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>. Two thirds of the patients were female. Most of the patients had cirrhosis, high baseline serum HCV RNA levels (> 800,000 iu/mL) and co-morbid diseases including diabetes mellitus, end stage renal disease, hepatocellular carcinoma, autoimmune diseases, non-Hodgkin lymphoma, thalassemia, hemophilia and hepatitis B co-infection with decreasing order of frequency (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>). Eight patients were unresponsive to pegylated in-terferon/ribavirin plus telaprevir or boceprevir previously.<elsevierMultimedia ident="t0005"></elsevierMultimedia>Virologic responseAt week 4, HCV RNA levels became undetectable in 82% of the patients. Overall, 59/61 patients (96.7%) had undetectable HCV RNA at week 12 during treatment and 57/59 patients (96.6%) had undetectable HCV RNA at week 24 on treatment.<ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="u0030">•ITT analysis. SVR12 rates were 80% (12/15), 91% (20/22) and 93% (13/14) in interferon-ineligible/intolerant, non-responder and relapsed patients respectively (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>). Among cirrhotic patients, SVR12 rate was 86.5%.<elsevierMultimedia ident="t0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="u0035">•PP analysis. At 12th week after the end of treatment period, 12 (80%) interferon-ineligible/intolerant, 20 (95.2%) non-responder and 13 (100%) relapsed patients had achieved SVR12. Patients with cirrhosis also achieved high rates of SVR12 (32/35, 91.4%).</li></ul>SVR12 rates were 83.3% (5/6) and 87.5 (7/8) in patients with end stage renal disease and previous protease inhibitor experience, respectively. SVR was not associated with sex, age or baseline HCV RNA levels.Virologic failureFour patients in treatment-experienced group had vi-rologic failures. Three of 4 were cirrhotic whereas 1 was non-cirrhotic. Two patients with undetectable HCV RNA at the 4th week of treatment had virologic breakthrough whereas 2 patients experienced viral relapse during post-treatment follow-up (<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>). One of the non-responder had obesity and the other had insulin resistance. Among the remaining, one patient had chronic renal failure, whereas the other had no any accompanying diseases.<elsevierMultimedia ident="t0015"></elsevierMultimedia>We could investigate pretreatment resistance-associated variants in 23 patients from one center in this study. Only one of those 23 patients had pretreatment Y93H polymorphism (HCV RNA levels were negative at 4th and 12th weeks of treatment, but the patient died at the 13th week of treatment). Of the 22 patients without baseline polymorphism one had virologic breakthrough and the other had post-treatment viral relapse.Improvement in liver biochemical testsTwelve weeks after treatment, all liver tests including ALT, AST, albumin, bilirubin and INR, and platelet counts improved significantly in the patients (<a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>). These results suggest that viral eradication by interferon-free daclatasvir and asunaprevir dual therapy also leads improvement in liver biochemical parameters.<elsevierMultimedia ident="t0020"></elsevierMultimedia>SafetyA total of 57 patients completed 24 weeks of therapy. Two patients died during the study period. Both deaths occurred at the 12-14th weeks of treatment as a result of underlying diseases including tuberculous meningitis in one and systemic vasculitis in the other. Both had unde-tectable HCV RNA at week 8 and 12 on treatment.None of the patients discontinued treatment due to any adverse events. The most common adverse event was dyspepsia (<a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>). There was no serious adverse event or any grade-4 laboratory abnormality.<elsevierMultimedia ident="t0025"></elsevierMultimedia>Cost effectivityCurrently, total cost of 24-week daclatasvir and asuna-previr dual therapy in Turkey is about 13.500 US dollars (present in the market but not paid by social security institution yet). Treatment of genotype 1b HCV infection with daclatasvir and asunaprevir dual therapy provided cost saving and health gain compared to the available treatment regimens.In treatment-naïve patients, for life years gained (LYG), dual therapy was more cost-effective than pegylated interferon + ribavirin (-1.100 US dollars), boceprevir + pegylated interferon + ribavirin (-4.764 US dollars), telaprevir + pegylated interferon + ribavirin (-7.843 US dollars) and without-treatment (-1.000 US dollars).In treatment-experienced patients, for LYG, dual therapy was also superior to pegylated interferon + ribavirin (-1.300 US dollars), boceprevir + pegylated interferon + ribavirin (-5.000 US dollars), telaprevir + pegylated interferon + ribavirin (-3.500 US dollars) and without-treatment (-400 US dollars).Quality adjusted life years (QALYs) analysis for dual therapy was also better than all other available alternatives.DiscussionIn this study, we demonstrated that daclatasvir-asuna-previr combination therapy is highly effective and safe in Turkish patients with chronic HCV. Daclatasvir-asuna-previr dual therapy seems to be successfull even in hard-to-treat patients with chronic renal failure under hemodialysis and protease inhibitor experience.As initial enrollment criteria, most of our patients had problematic baseline characteristics such as prior treatment, high serum HCV RNA, cirrhosis and accompanying diseases. However, SVR was more than 90% irrespective of any poor prognostic signs for HCV treatment.Response to dual therapy is affected mainly by daclatasvir resistance associated polymorphism<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a> SVR12 in patients without baseline NS5A (daclatasvir) resistance associated polymorphism has been reported as 90-100%, wheras it decreases dramatically to less than 40% in the presence of such polymorphism at baseline.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Fortunately, frequency of NS5A polymorphism seems to be less than 20% in Japanese and non-Japanese population with HCV infection.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> However that knowledge needs further validation especially in non-Japanese patients. In our study we could analyze baseline NS5A resistance associated polymorphism in 23 patients. There was only one polymorphism and it was in the dead patient who had undetectable serum HCV RNA at 4th and 12th weeks of treatment.One of the main advantage of daclatasvir and asunapre-vir dual therapy is absence of contraindication in patients with chronic renal failure. There are few data regarding safety of oral antiviral drugs in those patients. Ombitasvir-paritaprevir-ritonavir-dasabuvir and graziprevir-elbasvir combinations seem to be safe, whereas there is lack of evidence of sofosbuvir safety in chronic renal disease pa-tients.<a class="elsevierStyleCrossRefs" href="#bib0070">14-18</a> Reports demonstrated that daclatasvir and asunaprevir dual therapy is also safe in those patients. According to a recent study, 20 of 21 (95.5%) chronic hemo-dialysis patients using daclatasvir plus asunaprevir developed sustained virologic response.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Our data is also supporting both efficacy and safety of dual therapy in patients with chronic renal failure. Five of 6 patients had SVR and none had any adverse effects during the 24 week treatment duration.There is limited data about the efficacy of oral antiviral agents in patients with previous protease inhibitor experience. The underlying logic is that previous protease inhibitor (NS3/4) use would increase the risk of resistance. Although the frequency of NS3/4 resistance is very low and the resistance may disappear with time, the sponsors of registration clinical trials do not want to enroll those patient groups. Actually several reports of oral antiviral combinations including sofosbuvir-simeprevir combination have depicted that previous protease inhibitor experience did not have significant importance in respect to resistance and virological response.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Although study protocol did not allow enrollment of patients who were unresponsive to previous telaprevir or boceprevir treatment, 8 included patients had such a history and 7 of 8 patients had SVR in the present study.Daclatasvir and asunaprevir have a good safety profile.<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> Headache, fatigue, diarrhea, nausea and asthenia are the most frequently reported symptoms that occur in less than one fourth of the patients. A transient increment of liver transaminases and bilirubin attributed to asunaprevir have been reported in about 5-29% of patients.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> However, those rare adverse events did not cause to stop treatment in most of those patients. Interestingly none of our patients had transaminase elevations. Also, none of the patients had to stop the dual therapy as a result of any adverse events.Although some pretreatment variables such as viral load, presence of cirrhosis, age and insulin resistance had negative effect on SVR with interferon-ribavirin treatment of HCV,<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a> those factors seem to have less affect SVR with recent antiviral therapies. Since the number of the patients without SVR was too low in the present study, it is hard to speculate the pretreatment variables associated with viral failure.In conclusion, successful viral eradication by interfer-on-free daclatasvir and asunaprevir dual therapy leads to high sustained viral response in difficult to treat patient population. No serious adverse events or any adverse event resulting in discontinuation of therapy is reported." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1198049" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Aim" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Material and Methods" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abs0030" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1116693" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Treatment" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "s0030" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0035" "titulo" => "Patient characteristics before daclatasvir plus asunaprevir treatment" ] 1 => array:2 [ "identificador" => "s0040" "titulo" => "Virologic response" ] 2 => array:2 [ "identificador" => "s0045" "titulo" => "Virologic failure" ] 3 => array:2 [ "identificador" => "s0050" "titulo" => "Improvement in liver biochemical tests" ] 4 => array:2 [ "identificador" => "s0055" "titulo" => "Safety" ] 5 => array:2 [ "identificador" => "s0060" "titulo" => "Cost effectivity" ] ] ] 5 => array:2 [ "identificador" => "s0065" "titulo" => "Discussion" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-25" "fechaAceptado" => "2016-07-03" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1116693" "palabras" => array:3 [ 0 => "Chronic C hepatitis" 1 => "Daclatasvir" 2 => "Asunaprevir" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundDaclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. AimTo evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and MethodsSixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. ResultsFifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. ConclusionsDaclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Aim" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Material and Methods" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abs0030" "titulo" => "Conclusions" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "DM: diabetes mellitus. ESRD: end stage renal disease. HCC: hepatocellu-lar carcinoma. IFN: interferon. PI: protease inhibitor." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N = 61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (65.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (34.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.6 ± 12.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m2), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.8 ± 4.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Time of diagnosis for HCV (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.67 ± 5.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accompanying disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.50% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.80% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.60% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoimmune diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.60% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thalassemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.40% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemophilia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.40% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-Hodgkin lymphoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.40% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV co-infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.70% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37/61 (60.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24/61 (39.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/61 (16.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PegIFN/Ribavirin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43/61 (70.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PegIFN/Ribavirin/PI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8/61 (13.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment response \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Relapser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14/51 (27.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-responder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22/51 (43.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN ineligible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/51 (29.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCV RNA (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 800.000 IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (45.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥ 800.000 IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (54.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (98.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT (IU/mL), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.8 ± 36.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST( IU/mL), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.3 ± 45.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Albumin (g/dL), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.93 ± 0.51 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine, mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.28 ± 1.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR, mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.14 ± 0.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemoglobin (g/dL), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.96 ± 1.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">WBC ( /mm3), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6,000 ± 4,200 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelet ( /mm3), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">166,000 ± 99,000 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046061.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patient demographics and laboratory findings." ] ] 1 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N = 61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SVR12 (n, %) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55/61 (90) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrosis status \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32/37 (86.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23/24 (95.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment history \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/10 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PegIFN/ribavirin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38/43 (88.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PegIFN/ribavirin/PI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7/8 (87.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment response \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Relapser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13/14 (93) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-responder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20/22 (91) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN ineligible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12/15 (80) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESRD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5/6 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal renal function \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50/55 (91) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 65 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17/20 (85) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 65 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38/41 (92.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19/21 (90.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36/40 (90) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viral load \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 800,000 IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/28 (89.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046062.png" ] ] ] ] "descripcion" => array:1 [ "en" => "SVR12 rates according to previous treatment history and cirrhosis status (ITT analysis)." ] ] 2 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Naive (N: 10) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment experienced (N: 51) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All patients without SVR (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">On-treatment virological breakthrough (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-treatment relapse (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cirrhotic (N: 37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-cirrhotic (N: 24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All patients without SVR12 (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">On treatment virological breakthrough (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-treatment relapse (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046063.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Reasons for not achieving SVR according to previous treatment and cirrhosis." ] ] 3 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blood tests (mean±SD) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P (95% CI) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.41 ± 36.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.96 ± 17.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p < 0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.04 ± 46.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.12 ± 14.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p < 0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Albumin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.00 ± 0,49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4,16 ± 0,44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p : 0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total bilirubin (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0,91 ± 0,56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0,77 ± 0,52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p : 0.037 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,09 ± 0,16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,06 ± 0,13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p : 0.021 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelet (/mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">170.377 ± 98.991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">181.415 ± 110.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p : 0.034 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046065.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Liver tests before and after treatment." ] ] 4 => array:7 [ "identificador" => "t0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Common adverse events \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N = 59 (28.8%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dry mouth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema and itching \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspepsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nausea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Headache \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Constipation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Upper respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serious adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinuation due to any adverse event \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinuation due to any laboratory abnormality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046064.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Safety profile of dual therapy in the early access pro¬gramme." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review article: safety and tolerability of direct-acting anti-viral agents in the new era of hepatitis C therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Banerjee D." 1 => "Reddy K.R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Aliment Pharmacol Ther" "serieFecha" => "2016" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination treatment with hepatitis C virus protease and NS5A inhibitors is effective against re-combinant genotype 1a, 2a, and 3a viruses" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Gottwein J.M." 1 => "Jensen S.B." 2 => "Li Y.P." 3 => "Ghanem L." 4 => "Scheel T.K." 5 => "Serre S.B." 6 => "Mikkelsen L." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.02164-12" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2013" "volumen" => "57" "paginaInicial" => "1291" "paginaFinal" => "1303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23274664" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multi-cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Manns M." 1 => "Pol S." 2 => "Jacobson I.M." 3 => "Marcellin P." 4 => "Gordon S.C." 5 => "Peng C.Y." 6 => "Chang T.T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(14)61059-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2014" "volumen" => "384" "paginaInicial" => "1597" "paginaFinal" => "1605" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25078304" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual therapy with the non-structural protein 5A inhibitor, daclatasvir, and the nonstruc-tural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Chayama K." 1 => "Takahashi S." 2 => "Toyota J." 3 => "Karino Y." 4 => "Ikeda K." 5 => "Ishikawa H." 6 => "Watanabe H." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.24724" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2012" "volumen" => "55" "paginaInicial" => "742" "paginaFinal" => "748" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21987462" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Suzuki Y." 1 => "Ikeda K." 2 => "Suzuki F." 3 => "Toyota J." 4 => "Karino Y." 5 => "Chayama K." 6 => "Kawakami Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2012.09.037" "Revista" => array:6 [ "tituloSerie" => ". J Hepatol" "fecha" => "2013" "volumen" => "58" "paginaInicial" => "655" "paginaFinal" => "662" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23183526" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Daclatasvir and asunaprevir treatment improves liver function parameters and reduces liver fibrosis markers in chronic hepatitis C patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Miyaki E." 1 => "Imamura M." 2 => "Hiraga N." 3 => "Murakami E." 4 => "Kawaoka T." 5 => "Tsuge M." 6 => "Hiramatsu A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Hepatol Res" "serieFecha" => "2015" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Kumada H." 1 => "Suzuki Y." 2 => "Ikeda K." 3 => "Toyota J." 4 => "Karino Y." 5 => "Chayama K." 6 => "Kawakami Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.27113" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2014" "volumen" => "59" "paginaInicial" => "2083" "paginaFinal" => "2091" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24604476" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Daclatasvir Plus Asunaprevir for HCV Genotype 1b Infection in Patients With or Without Compensated Cirrhosis: A Pooled Analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Kao J.H." 1 => "Jensen D.M." 2 => "Manns M.P." 3 => "Jacobson I." 4 => "Kumada H." 5 => "Toyota J." 6 => "Heo J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Liver Int" "serieFecha" => "2015" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of da-clatasvir and asunaprevir combination therapy in chronic he-modialysis patients with chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Suda G." 1 => "Kudo M." 2 => "Nagasaka A." 3 => "Furuya K." 4 => "Yamamoto Y." 5 => "Kobayashi T." 6 => "Shinada K." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "J Gastroenterol" "serieFecha" => "2016" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Daclatasvir and asunaprevir for recurrent hepatitis c following living-donor liver transplantation with human immunodeficiency virus coinfection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Tanaka T." 1 => "Akamatsu N." 2 => "Kaneko J." 3 => "Arita J." 4 => "Tamura S." 5 => "Haseg-awa K." 6 => "Sakamoto Y." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Hepatol Res" "serieFecha" => "2015" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation: Case report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Kawaoka T." 1 => "Imamura M." 2 => "Morio K." 3 => "Nakamura Y." 4 => "Tsuge M." 5 => "Nelson Hayes C." 6 => "Kawakami Y." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Hepatol Res" "serieFecha" => "2015" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High sustained virologic response to daclatasvir plus asunaprevir in elderly and cirrhotic patients with hepatitis C virus genotype 1b without baseline NS5A polymorphisms" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "McPhee F." 1 => "Suzuki Y." 2 => "Toyota J." 3 => "Karino Y." 4 => "Chayama K." 5 => "Kawakami Y." 6 => "Yu M.L." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12325-015-0221-5" "Revista" => array:6 [ "tituloSerie" => "Adv Ther" "fecha" => "2015" "volumen" => "32" "paginaInicial" => "637" "paginaFinal" => "649" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26155891" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed da-clatasvir and asunaprevir therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Yoshimi S." 1 => "Imamura M." 2 => "Murakami E." 3 => "Hiraga N." 4 => "Tsuge M." 5 => "Kawakami Y." 6 => "Aikata H." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.24255" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2015" "volumen" => "87" "paginaInicial" => "1913" "paginaFinal" => "1920" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25954851" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HCV and the kidney" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Corouge M." 1 => "Vallet-Pichard A." 2 => "Pol S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/liv.13022" "Revista" => array:7 [ "tituloSerie" => "Liver Int" "fecha" => "2016" "volumen" => "36" "numero" => "Suppl. 1" "paginaInicial" => "28" "paginaFinal" => "33" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26725894" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of Ombi- tasvir/ Paritaprevir/Ritonavir + Dasabuvir for treating HCV GT1 infection in patients with severe renal impairment or end-stage renal disease: the RUBY-1 study. EASL 2015" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Pockros P.J." 1 => "Reddy K.R." 2 => "Mantry P.S." 3 => "Cohen E." 4 => "Bennett M." 5 => "Sulkowski M.S." 6 => "Bernstein D." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "62" "paginaInicial" => "S257" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Roth D." 1 => "Nelson D." 2 => "Burchfeld A." 3 => "Liapakis A." 4 => "Silva M." 5 => "Monsour H." 6 => "Martin P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(15)00349-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2015" "volumen" => "386" "paginaInicial" => "1537" "paginaFinal" => "1545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26456905" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety, and anti- viral efficacy and pharma-cokinetics (PK) of sofosbuvir (SOF) in patients with severe renal impairment. AASLD 2014" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Gane E.J." 1 => "Robson R.A." 2 => "Bonacini M." 3 => "Maliakkal B." 4 => "Kirby B." 5 => "Liu L." 6 => "Sajvani K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.27163" "Revista" => array:4 [ "tituloSerie" => "Hepatology" "fecha" => "2014" "volumen" => "60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24715633" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function: real-world experience from HCV-target. EASL 2015" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Saxena V." 1 => "Koraishy F.M." 2 => "Sise M." 3 => "Lim J.K." 4 => "Schmidt M." 5 => "Chung R.T." 6 => "Liapakis D.R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "62" "paginaInicial" => "S267" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Childs-Kean L.M." 1 => "Hand E.O." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinthera.2014.12.012" "Revista" => array:6 [ "tituloSerie" => "Clin Ther" "fecha" => "2015" "volumen" => "37" "paginaInicial" => "243" "paginaFinal" => "267" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25601269" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized comparison of daclatasvir + asunaprevir versus telaprevir + peginterferon/ribavirin in Japanese hepatitis C virus patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Kumada H." 1 => "Suzuki F." 2 => "Suzuki Y." 3 => "Toyota J." 4 => "Karino Y." 5 => "Chayama K." 6 => "Kawakami Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jgh.13349" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2016" "volumen" => "31" "paginaInicial" => "14" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26990906" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." 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Seyfettin Köklü

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gskoklu@yahoo.com

Correspondence and reprint request:

, Iftihar Köksal†, Ulus Salih Akarca‡, Ayhan Balkan§, Rahmet Güner||, Aylin Demirezen¶, Memduh Sahin**, Sila Akhan††, Reşat Ozaras‡‡, Ramazan Idilman§§

* Department of Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey

† Department of Infectious Disease, Karadeniz University School of Medicine, Trabzon, Turkey

‡ Department of Gastroenterology, Ege University School of Medicine, Izmir, Turkey

§ Department of Gastroenterology, Gaziantep University School of Medicine, Gazianatep, Turkey

|| Department of Infectious Diseases and Clinical Microbiology, Yildirim Beyazit University School of Medicine, Ankara, Turkey

¶ Department of Gastroenterology, Atatürk Education and Research Hospital, Ankara, Turkey

** Department of Gastroenterology, Mersin Government Hospital, Mersin, Turkey

†† Department of Gastroenterology, Kocaeli University School of Medicine, Kocaeli, Turkey

‡‡ Department of Infectious Disease, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey

§§ Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Currently&#44; treatment of chronic hepatitis C virus&#40;HCV&#41; infection includes interferon free regimens&#46; Directacting antiviral drugs are taken orally and consists of three major subgroups including protease and polymerase inhibitors&#44; and the multifunctional non-structural protein &#40;NS5A&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Asunaprevir is a non-structural NS3&#47;4A complex protease inhibitor and daclatasvir is a pangenotypic NS5A inhibitor of HCV replication complex&#46; Combination of asunaprevir and daclatasvir has potent activity against genotype 1b HCV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Daclatasvir plus asunaprevir combination has been first approved for the treatment of genoype 1b subgroup in Japan&#46; Recently&#44; Korea&#44; Taiwan&#44; Canada and Turkey have also approved that dual therapy with similar indications&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">Phase II and III studies showed potent antiviral affects using daclatasvir and asunaprevir combination in patients infected with HCV genotype 1b&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3-6</span></a> In the Japan phase 3 study&#44; SVR<span class="elsevierStyleInf">24</span> in Japanese patients were 91&#37; and 84&#37; in cir-rhotics and non-cirrhotics respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> A recent pooled analysis have reported that SVR<span class="elsevierStyleInf">12</span> was 84&#37; in patients with cirrhosis and 85&#37; in patients without cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">Preliminary data demonstrated the efficacy and safety of dual therapy even in hard to treat patients including patients with cirrhosis&#44; liver transplantation and chronic renal failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9-11</span></a> However&#44; efficacy and safety data of daclatasvir and asunaprevir combination therapy is scarce other than Japanese studies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Herein&#44; we evaluated the antiviral activity and safety of daclatasvir and asunaprevir combination therapy in Turkish patients infected with HCV genotype 1b&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Study design</span><p id="p0030" class="elsevierStylePara elsevierViewall">The study includes the results of patients enrolled in early access program of BMS in Turkey&#46; Inclusion criteria allowed only the patients who were considered to have a serious or life-threatening condition that was impacting life expectancy within 12 months&#46; Patients having Child B or C cirrhosis&#44; or having liver-transplantation history were not allowed to be enrolled into the program&#46; Request forms filled by healthcare professionals were submitted for both BMS company and health authority approval&#46; All patients signed the informed consent forms before the treatment&#46; The program started at February 2014 and ended in August 2014&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Treatment</span><p id="p0035" class="elsevierStylePara elsevierViewall">Dual therapy was provided before commercialization in early access program&#46; All patients received daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks unless a viral breakthrough developed&#46; All patients were visited at each 4 week during the treatment period and at the 12th week after treatment&#46; Biochemical tests&#44; complete blood count&#44; coagulation tests and HCV RNA were tested at each visit&#46; HCV RNA was tested once more when it became positive suggesting viral breakthrough or recurrence&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCV RNA assessment&#46;</span> Hepatitis C virus RNA was quantified using the Roche COBAS&#174; TaqMan&#174; assay with an LLOQ of 15 IU&#47;mL&#46;</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Resistance analysis&#46;</span> Direct sequencing from baseline samples was performed in a group of patients from one center &#40;23 patients&#41;&#46; Only NS5A resistance was analysed in that group&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Efficacy&#46;</span> Sustained virologic response &#40;SVR<span class="elsevierStyleInf">12</span>&#41; at post-treatment week 12&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Safety assessments&#46;</span> Based on incidence of adverse events &#40;AE&#41;&#44; serious adverse events &#40;SAE&#41;&#44; discontinuations because of adverse events&#44; and grade 3 or 4 laboratory abnormalities&#46; Adverse events were recorded at each 4-week visit during study follow-up&#46;</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Cost effectivity&#46;</span> Markov simulation model was used to estimate the cost-effectiveness of dual therapy&#44; and the effectivity was compared with available treatment regimens paid by social security institution in Turkey &#40;pegylated interferon&#43;ribavirin &#177; telaprevir or bo- ceprevir&#41;&#46;</p></li></ul></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Statistical analysis</span><p id="p0070" class="elsevierStylePara elsevierViewall">Continuous variables were analyzed using the Mann-Whitney <span class="elsevierStyleItalic">U-</span>test&#44; and categorical variables were analyzed using the paired sample test&#46; All statistical analyses were performed using the SPSS software package &#40;version 16&#46;0 for Windows&#44; SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#44; with p &#60; 0&#46;05 denoting statistical significance&#46;</p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Results</span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Patient characteristics before daclatasvir plus asunaprevir treatment</span><p id="p0075" class="elsevierStylePara elsevierViewall">Fifty-seven patients completed 24 weeks of dual treatment&#46; Two patients died at 12-14th week of treatment as a consequence of miliary tuberculosis in one and systemic vasculitis in the other&#46; Both were HCV RNA negative at week 8 and 12&#46; Ten were treatment-na&#239;ve&#44; 15 were in the interferon-ineligible&#47;intolerant group&#44; 14 were relapser and 22 were in the non-responder group &#40;null responders and partial responders&#41;&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">Demographic baseline and laboratory characteristics of patients are shown in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>&#46; Two thirds of the patients were female&#46; Most of the patients had cirrhosis&#44; high baseline serum HCV RNA levels &#40;&#62; 800&#44;000 iu&#47;mL&#41; and co-morbid diseases including diabetes mellitus&#44; end stage renal disease&#44; hepatocellular carcinoma&#44; autoimmune diseases&#44; non-Hodgkin lymphoma&#44; thalassemia&#44; hemophilia and hepatitis B co-infection with decreasing order of frequency &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Eight patients were unresponsive to pegylated in-terferon&#47;ribavirin plus telaprevir or boceprevir previously&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Virologic response</span><p id="p0085" class="elsevierStylePara elsevierViewall">At week 4&#44; HCV RNA levels became undetectable in 82&#37; of the patients&#46; Overall&#44; 59&#47;61 patients &#40;96&#46;7&#37;&#41; had undetectable HCV RNA at week 12 during treatment and 57&#47;59 patients &#40;96&#46;6&#37;&#41; had undetectable HCV RNA at week 24 on treatment&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ITT analysis&#46;</span> SVR<span class="elsevierStyleInf">12</span> rates were 80&#37; &#40;12&#47;15&#41;&#44; 91&#37; &#40;20&#47;22&#41; and 93&#37; &#40;13&#47;14&#41; in interferon-ineligible&#47;intolerant&#44; non-responder and relapsed patients respectively &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46; Among cirrhotic patients&#44; SVR<span class="elsevierStyleInf">12</span> rate was 86&#46;5&#37;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">PP analysis&#46;</span> At 12th week after the end of treatment period&#44; 12 &#40;80&#37;&#41; interferon-ineligible&#47;intolerant&#44; 20 &#40;95&#46;2&#37;&#41; non-responder and 13 &#40;100&#37;&#41; relapsed patients had achieved SVR<span class="elsevierStyleInf">12</span>&#46; Patients with cirrhosis also achieved high rates of SVR<span class="elsevierStyleInf">12</span> &#40;32&#47;35&#44; 91&#46;4&#37;&#41;&#46;</p></li></ul></p><p id="p0105" class="elsevierStylePara elsevierViewall">SVR<span class="elsevierStyleInf">12</span> rates were 83&#46;3&#37; &#40;5&#47;6&#41; and 87&#46;5 &#40;7&#47;8&#41; in patients with end stage renal disease and previous protease inhibitor experience&#44; respectively&#46; SVR was not associated with sex&#44; age or baseline HCV RNA levels&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Virologic failure</span><p id="p0110" class="elsevierStylePara elsevierViewall">Four patients in treatment-experienced group had vi-rologic failures&#46; Three of 4 were cirrhotic whereas 1 was non-cirrhotic&#46; Two patients with undetectable HCV RNA at the 4th week of treatment had virologic breakthrough whereas 2 patients experienced viral relapse during post-treatment follow-up &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#41;&#46; One of the non-responder had obesity and the other had insulin resistance&#46; Among the remaining&#44; one patient had chronic renal failure&#44; whereas the other had no any accompanying diseases&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><p id="p0115" class="elsevierStylePara elsevierViewall">We could investigate pretreatment resistance-associated variants in 23 patients from one center in this study&#46; Only one of those 23 patients had pretreatment Y93H polymorphism &#40;HCV RNA levels were negative at 4th and 12th weeks of treatment&#44; but the patient died at the 13th week of treatment&#41;&#46; Of the 22 patients without baseline polymorphism one had virologic breakthrough and the other had post-treatment viral relapse&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Improvement in liver biochemical tests</span><p id="p0120" class="elsevierStylePara elsevierViewall">Twelve weeks after treatment&#44; all liver tests including ALT&#44; AST&#44; albumin&#44; bilirubin and INR&#44; and platelet counts improved significantly in the patients &#40;<a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>&#41;&#46; These results suggest that viral eradication by interferon-free daclatasvir and asunaprevir dual therapy also leads improvement in liver biochemical parameters&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Safety</span><p id="p0125" class="elsevierStylePara elsevierViewall">A total of 57 patients completed 24 weeks of therapy&#46; Two patients died during the study period&#46; Both deaths occurred at the 12-14th weeks of treatment as a result of underlying diseases including tuberculous meningitis in one and systemic vasculitis in the other&#46; Both had unde-tectable HCV RNA at week 8 and 12 on treatment&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">None of the patients discontinued treatment due to any adverse events&#46; The most common adverse event was dyspepsia &#40;<a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>&#41;&#46; There was no serious adverse event or any grade-4 laboratory abnormality&#46;</p><elsevierMultimedia ident="t0025"></elsevierMultimedia></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Cost effectivity</span><p id="p0135" class="elsevierStylePara elsevierViewall">Currently&#44; total cost of 24-week daclatasvir and asuna-previr dual therapy in Turkey is about 13&#46;500 US dollars &#40;present in the market but not paid by social security institution yet&#41;&#46; Treatment of genotype 1b HCV infection with daclatasvir and asunaprevir dual therapy provided cost saving and health gain compared to the available treatment regimens&#46;</p><p id="p0140" class="elsevierStylePara elsevierViewall">In treatment-na&#239;ve patients&#44; for life years gained &#40;LYG&#41;&#44; dual therapy was more cost-effective than pegylated interferon &#43; ribavirin &#40;-1&#46;100 US dollars&#41;&#44; boceprevir &#43; pegylated interferon &#43; ribavirin &#40;-4&#46;764 US dollars&#41;&#44; telaprevir &#43; pegylated interferon &#43; ribavirin &#40;-7&#46;843 US dollars&#41; and without-treatment &#40;-1&#46;000 US dollars&#41;&#46;</p><p id="p0145" class="elsevierStylePara elsevierViewall">In treatment-experienced patients&#44; for LYG&#44; dual therapy was also superior to pegylated interferon &#43; ribavirin &#40;-1&#46;300 US dollars&#41;&#44; boceprevir &#43; pegylated interferon &#43; ribavirin &#40;-5&#46;000 US dollars&#41;&#44; telaprevir &#43; pegylated interferon &#43; ribavirin &#40;-3&#46;500 US dollars&#41; and without-treatment &#40;-400 US dollars&#41;&#46;</p><p id="p0150" class="elsevierStylePara elsevierViewall">Quality adjusted life years &#40;QALYs&#41; analysis for dual therapy was also better than all other available alternatives&#46;</p></span></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Discussion</span><p id="p0155" class="elsevierStylePara elsevierViewall">In this study&#44; we demonstrated that daclatasvir-asuna-previr combination therapy is highly effective and safe in Turkish patients with chronic HCV&#46; Daclatasvir-asuna-previr dual therapy seems to be successfull even in hard-to-treat patients with chronic renal failure under hemodialysis and protease inhibitor experience&#46;</p><p id="p0160" class="elsevierStylePara elsevierViewall">As initial enrollment criteria&#44; most of our patients had problematic baseline characteristics such as prior treatment&#44; high serum HCV RNA&#44; cirrhosis and accompanying diseases&#46; However&#44; SVR was more than 90&#37; irrespective of any poor prognostic signs for HCV treatment&#46;</p><p id="p0165" class="elsevierStylePara elsevierViewall">Response to dual therapy is affected mainly by daclatasvir resistance associated polymorphism<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> SVR<span class="elsevierStyleInf">12</span> in patients without baseline NS5A &#40;daclatasvir&#41; resistance associated polymorphism has been reported as 90-100&#37;&#44; wheras it decreases dramatically to less than 40&#37; in the presence of such polymorphism at baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Fortunately&#44; frequency of NS5A polymorphism seems to be less than 20&#37; in Japanese and non-Japanese population with HCV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However that knowledge needs further validation especially in non-Japanese patients&#46; In our study we could analyze baseline NS5A resistance associated polymorphism in 23 patients&#46; There was only one polymorphism and it was in the dead patient who had undetectable serum HCV RNA at 4th and 12th weeks of treatment&#46;</p><p id="p0170" class="elsevierStylePara elsevierViewall">One of the main advantage of daclatasvir and asunapre-vir dual therapy is absence of contraindication in patients with chronic renal failure&#46; There are few data regarding safety of oral antiviral drugs in those patients&#46; Ombitasvir-paritaprevir-ritonavir-dasabuvir and graziprevir-elbasvir combinations seem to be safe&#44; whereas there is lack of evidence of sofosbuvir safety in chronic renal disease pa-tients&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14-18</span></a> Reports demonstrated that daclatasvir and asunaprevir dual therapy is also safe in those patients&#46; According to a recent study&#44; 20 of 21 &#40;95&#46;5&#37;&#41; chronic hemo-dialysis patients using daclatasvir plus asunaprevir developed sustained virologic response&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Our data is also supporting both efficacy and safety of dual therapy in patients with chronic renal failure&#46; Five of 6 patients had SVR and none had any adverse effects during the 24 week treatment duration&#46;</p><p id="p0175" class="elsevierStylePara elsevierViewall">There is limited data about the efficacy of oral antiviral agents in patients with previous protease inhibitor experience&#46; The underlying logic is that previous protease inhibitor &#40;NS3&#47;4&#41; use would increase the risk of resistance&#46; Although the frequency of NS3&#47;4 resistance is very low and the resistance may disappear with time&#44; the sponsors of registration clinical trials do not want to enroll those patient groups&#46; Actually several reports of oral antiviral combinations including sofosbuvir-simeprevir combination have depicted that previous protease inhibitor experience did not have significant importance in respect to resistance and virological response&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Although study protocol did not allow enrollment of patients who were unresponsive to previous telaprevir or boceprevir treatment&#44; 8 included patients had such a history and 7 of 8 patients had SVR in the present study&#46;</p><p id="p0180" class="elsevierStylePara elsevierViewall">Daclatasvir and asunaprevir have a good safety profile&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> Headache&#44; fatigue&#44; diarrhea&#44; nausea and asthenia are the most frequently reported symptoms that occur in less than one fourth of the patients&#46; A transient increment of liver transaminases and bilirubin attributed to asunaprevir have been reported in about 5-29&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> However&#44; those rare adverse events did not cause to stop treatment in most of those patients&#46; Interestingly none of our patients had transaminase elevations&#46; Also&#44; none of the patients had to stop the dual therapy as a result of any adverse events&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">Although some pretreatment variables such as viral load&#44; presence of cirrhosis&#44; age and insulin resistance had negative effect on SVR with interferon-ribavirin treatment of HCV&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> those factors seem to have less affect SVR with recent antiviral therapies&#46; Since the number of the patients without SVR was too low in the present study&#44; it is hard to speculate the pretreatment variables associated with viral failure&#46;</p><p id="p0190" class="elsevierStylePara elsevierViewall">In conclusion&#44; successful viral eradication by interfer-on-free daclatasvir and asunaprevir dual therapy leads to high sustained viral response in difficult to treat patient population&#46; No serious adverse events or any adverse event resulting in discontinuation of therapy is reported&#46;</p></span></span>"
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              "titulo" => "Background"
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          "titulo" => "Introduction"
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          "titulo" => "Results"
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              "titulo" => "Patient characteristics before daclatasvir plus asunaprevir treatment"
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              "titulo" => "Virologic response"
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            2 => array:2 [
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              "titulo" => "Virologic failure"
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            3 => array:2 [
              "identificador" => "s0050"
              "titulo" => "Improvement in liver biochemical tests"
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              "identificador" => "s0055"
              "titulo" => "Safety"
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              "titulo" => "Cost effectivity"
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          "titulo" => "Discussion"
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    "fechaRecibido" => "2016-05-25"
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            0 => "Chronic C hepatitis"
            1 => "Daclatasvir"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Background</span><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries&#46;</p></span> <span id="abs0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Aim</span><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients&#46;</p></span> <span id="abs0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program&#46; Most of the patients were in difficult-to-treat category&#46; Patients were visited at each 4 week throughout the follow-up period&#46; Laboratory findings and adverse events were recorded at each visit&#46;</p></span> <span id="abs0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Results</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Fifty-seven of 61 enrolled patients completed 24 weeks of treatment&#46; Two patients died as a result of underlying diseases at 12-14th weeks of treatment&#46; Two patients stopped the treatment early as a consequence of virological breakthrough&#44; and 2 patients had viral relapse at the post-treatment follow-up&#46; Overall SVR12 rates were 90&#37; &#40;55&#47;61&#41; and 93&#46;2&#37; &#40;55&#47;59&#41; according to intention-to-treat &#40;ITT&#41; and per protocol &#40;PP&#41; analysis respectively&#46; In ITT analysis&#44; SVR12 was achieved by 93&#37; &#40;13&#47;14&#41; in relapsers&#44; 80&#37; &#40;12&#47;15&#41; in interferon-ineligible patients and 91&#37; &#40;20&#47;22&#41; in previous nonresponder patients&#46; SVR<span class="elsevierStyleInf">12</span> rates were 86&#46;5&#37; and 91&#46;4&#37; in patients with cirrhosis according to ITT and PP analysis respectively&#46; SVR<span class="elsevierStyleInf">12</span> was 95&#46;8&#37; in non-cirrhosis group in both analysis&#46; Patients with previous protease inhibitor experience had an SVR<span class="elsevierStyleInf">12</span> of 87&#46;5&#37;&#46; Common adverse events developed in 28&#46;8&#37; of patients&#46; There were no treatment related severe adverse event or grade-4 laboratory abnormality&#46;</p></span> <span id="abs0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Conclusions</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection&#46;</p></span>"
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "DM&#58; diabetes mellitus&#46; ESRD&#58; end stage renal disease&#46; HCC&#58; hepatocellu-lar carcinoma&#46; IFN&#58; interferon&#46; PI&#58; protease inhibitor&#46;"
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N &#61; 61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;65&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;34&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;6 &#177; 12&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;8 &#177; 4&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time of diagnosis for HCV &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;67 &#177; 5&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Accompanying disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ESRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;80&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;60&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autoimmune diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;60&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thalassemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;40&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemophilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;40&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-Hodgkin lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;40&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HBV co-infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;70&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#47;61 &#40;60&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#47;61 &#40;39&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#47;61 &#40;16&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PegIFN&#47;Ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#47;61 &#40;70&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PegIFN&#47;Ribavirin&#47;PI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#47;61 &#40;13&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous treatment response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Relapser&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;51 &#40;27&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-responder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#47;51 &#40;43&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN ineligible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#47;51 &#40;29&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCV RNA &#40;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 800&#46;000 IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;45&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805; 800&#46;000 IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;54&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;98&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT &#40;IU&#47;mL&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;8 &#177; 36&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST&#40; IU&#47;mL&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;3 &#177; 45&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Albumin &#40;g&#47;dL&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;93 &#177; 0&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;28 &#177; 1&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;14 &#177; 0&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemoglobin &#40;g&#47;dL&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;96 &#177; 1&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">WBC &#40; &#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;000 &#177; 4&#44;200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelet &#40; &#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; mean &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166&#44;000 &#177; 99&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2046061.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Patient demographics and laboratory findings&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "t0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N &#61; 61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SVR<span class="elsevierStyleInf">12</span> &#40;n&#44; &#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#47;61 &#40;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrosis status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#47;37 &#40;86&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#47;24 &#40;95&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous treatment history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#47;10 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PegIFN&#47;ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#47;43 &#40;88&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PegIFN&#47;ribavirin&#47;PI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#47;8 &#40;87&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous treatment response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Relapser&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#47;14 &#40;93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-responder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#47;22 &#40;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN ineligible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#47;15 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ESRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#47;6 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal renal function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#47;55 &#40;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62; 65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#47;20 &#40;85&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#47;41 &#40;92&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#47;21 &#40;90&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#47;40 &#40;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Viral load&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 800&#44;000 IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#47;28 &#40;89&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2046062.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">SVR<span class="elsevierStyleInf">12</span> rates according to previous treatment history and cirrhosis status &#40;ITT analysis&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "t0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Naive &#40;N&#58; 10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment experienced &#40;N&#58; 51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients without SVR &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">On-treatment virological breakthrough &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-treatment relapse &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cirrhotic &#40;N&#58; 37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-cirrhotic &#40;N&#58; 24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients without SVR<span class="elsevierStyleInf">12</span> &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">On treatment virological breakthrough &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-treatment relapse &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2046063.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Reasons for not achieving SVR according to previous treatment and cirrhosis&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "t0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blood tests &#40;mean&#177;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT &#40;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;41 &#177; 36&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#46;96 &#177; 17&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST &#40;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;04 &#177; 46&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;12 &#177; 14&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Albumin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;00 &#177; 0&#44;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;16 &#177; 0&#44;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#58; 0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total bilirubin &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;91 &#177; 0&#44;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;77 &#177; 0&#44;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#58; 0&#46;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;09 &#177; 0&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;06 &#177; 0&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#58; 0&#46;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelet &#40;&#47;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">170&#46;377 &#177; 98&#46;991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">181&#46;415 &#177; 110&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p &#58; 0&#46;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2046065.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Liver tests before and after treatment&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "t0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Common adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N &#61; 59 &#40;28&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dry mouth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erythema and itching&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Constipation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upper respiratory tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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      "titulo" => "References"
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          "identificador" => "bs0010"
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              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review article&#58; safety and tolerability of direct-acting anti-viral agents in the new era of hepatitis C therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Banerjee D&#46;"
                            1 => "Reddy K&#46;R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "Aliment Pharmacol Ther"
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                  ]
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              ]
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            1 => array:3 [
              "identificador" => "bib0010"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Combination treatment with hepatitis C virus protease and NS5A inhibitors is effective against re-combinant genotype 1a&#44; 2a&#44; and 3a viruses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Gottwein J&#46;M&#46;"
                            1 => "Jensen S&#46;B&#46;"
                            2 => "Li Y&#46;P&#46;"
                            3 => "Ghanem L&#46;"
                            4 => "Scheel T&#46;K&#46;"
                            5 => "Serre S&#46;B&#46;"
                            6 => "Mikkelsen L&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.02164-12"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2013"
                        "volumen" => "57"
                        "paginaInicial" => "1291"
                        "paginaFinal" => "1303"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23274664"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b&#58; a multinational&#44; phase 3&#44; multi-cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Manns M&#46;"
                            1 => "Pol S&#46;"
                            2 => "Jacobson I&#46;M&#46;"
                            3 => "Marcellin P&#46;"
                            4 => "Gordon S&#46;C&#46;"
                            5 => "Peng C&#46;Y&#46;"
                            6 => "Chang T&#46;T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(14)61059-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2014"
                        "volumen" => "384"
                        "paginaInicial" => "1597"
                        "paginaFinal" => "1605"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25078304"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dual therapy with the non-structural protein 5A inhibitor&#44; daclatasvir&#44; and the nonstruc-tural protein 3 protease inhibitor&#44; asunaprevir&#44; in hepatitis C virus genotype 1b-infected null responders"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:7 [
                            0 => "Chayama K&#46;"
                            1 => "Takahashi S&#46;"
                            2 => "Toyota J&#46;"
                            3 => "Karino Y&#46;"
                            4 => "Ikeda K&#46;"
                            5 => "Ishikawa H&#46;"
                            6 => "Watanabe H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.24724"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2012"
                        "volumen" => "55"
                        "paginaInicial" => "742"
                        "paginaFinal" => "748"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21987462"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Suzuki Y&#46;"
                            1 => "Ikeda K&#46;"
                            2 => "Suzuki F&#46;"
                            3 => "Toyota J&#46;"
                            4 => "Karino Y&#46;"
                            5 => "Chayama K&#46;"
                            6 => "Kawakami Y&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2012.09.037"
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                        "tituloSerie" => "&#46; J Hepatol"
                        "fecha" => "2013"
                        "volumen" => "58"
                        "paginaInicial" => "655"
                        "paginaFinal" => "662"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23183526"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            5 => array:3 [
              "identificador" => "bib0030"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Daclatasvir and asunaprevir treatment improves liver function parameters and reduces liver fibrosis markers in chronic hepatitis C patients"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
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                            1 => "Imamura M&#46;"
                            2 => "Hiraga N&#46;"
                            3 => "Murakami E&#46;"
                            4 => "Kawaoka T&#46;"
                            5 => "Tsuge M&#46;"
                            6 => "Hiramatsu A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "Hepatol Res"
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              ]
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              "identificador" => "bib0035"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection"
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                          "autores" => array:7 [
                            0 => "Kumada H&#46;"
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                            2 => "Ikeda K&#46;"
                            3 => "Toyota J&#46;"
                            4 => "Karino Y&#46;"
                            5 => "Chayama K&#46;"
                            6 => "Kawakami Y&#46;"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.27113"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
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                        "paginaFinal" => "2091"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24604476"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0040"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Daclatasvir Plus Asunaprevir for HCV Genotype 1b Infection in Patients With or Without Compensated Cirrhosis&#58; A Pooled Analysis"
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                        0 => array:2 [
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                            3 => "Jacobson I&#46;"
                            4 => "Kumada H&#46;"
                            5 => "Toyota J&#46;"
                            6 => "Heo J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "Liver Int"
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                ]
              ]
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            8 => array:3 [
              "identificador" => "bib0045"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of da-clatasvir and asunaprevir combination therapy in chronic he-modialysis patients with chronic hepatitis C"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Suda G&#46;"
                            1 => "Kudo M&#46;"
                            2 => "Nagasaka A&#46;"
                            3 => "Furuya K&#46;"
                            4 => "Yamamoto Y&#46;"
                            5 => "Kobayashi T&#46;"
                            6 => "Shinada K&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "J Gastroenterol"
                        "serieFecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Daclatasvir and asunaprevir for recurrent hepatitis c following living-donor liver transplantation with human immunodeficiency virus coinfection"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Tanaka T&#46;"
                            1 => "Akamatsu N&#46;"
                            2 => "Kaneko J&#46;"
                            3 => "Arita J&#46;"
                            4 => "Tamura S&#46;"
                            5 => "Haseg-awa K&#46;"
                            6 => "Sakamoto Y&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "Hepatol Res"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation&#58; Case report"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Kawaoka T&#46;"
                            1 => "Imamura M&#46;"
                            2 => "Morio K&#46;"
                            3 => "Nakamura Y&#46;"
                            4 => "Tsuge M&#46;"
                            5 => "Nelson Hayes C&#46;"
                            6 => "Kawakami Y&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "Hepatol Res"
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                  ]
                ]
              ]
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            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High sustained virologic response to daclatasvir plus asunaprevir in elderly and cirrhotic patients with hepatitis C virus genotype 1b without baseline NS5A polymorphisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "McPhee F&#46;"
                            1 => "Suzuki Y&#46;"
                            2 => "Toyota J&#46;"
                            3 => "Karino Y&#46;"
                            4 => "Chayama K&#46;"
                            5 => "Kawakami Y&#46;"
                            6 => "Yu M&#46;L&#46;"
                          ]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12325-015-0221-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Ther"
                        "fecha" => "2015"
                        "volumen" => "32"
                        "paginaInicial" => "637"
                        "paginaFinal" => "649"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26155891"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed da-clatasvir and asunaprevir therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "Yoshimi S&#46;"
                            1 => "Imamura M&#46;"
                            2 => "Murakami E&#46;"
                            3 => "Hiraga N&#46;"
                            4 => "Tsuge M&#46;"
                            5 => "Kawakami Y&#46;"
                            6 => "Aikata H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jmv.24255"
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                        "tituloSerie" => "J Med Virol"
                        "fecha" => "2015"
                        "volumen" => "87"
                        "paginaInicial" => "1913"
                        "paginaFinal" => "1920"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25954851"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            13 => array:3 [
              "identificador" => "bib0070"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HCV and the kidney"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Corouge M&#46;"
                            1 => "Vallet-Pichard A&#46;"
                            2 => "Pol S&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/liv.13022"
                      "Revista" => array:7 [
                        "tituloSerie" => "Liver Int"
                        "fecha" => "2016"
                        "volumen" => "36"
                        "numero" => "Suppl&#46; 1"
                        "paginaInicial" => "28"
                        "paginaFinal" => "33"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26725894"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0075"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety of Ombi- tasvir&#47; Paritaprevir&#47;Ritonavir &#43; Dasabuvir for treating HCV GT1 infection in patients with severe renal impairment or end-stage renal disease&#58; the RUBY-1 study&#46; EASL 2015"
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                          "autores" => array:7 [
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                            3 => "Cohen E&#46;"
                            4 => "Bennett M&#46;"
                            5 => "Sulkowski M&#46;S&#46;"
                            6 => "Bernstein D&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Hepatol"
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                        "paginaInicial" => "S257"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4&#8211;5 chronic kidney disease &#40;the C-SURFER study&#41;&#58; a combination phase 3 study"
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                            2 => "Burchfeld A&#46;"
                            3 => "Liapakis A&#46;"
                            4 => "Silva M&#46;"
                            5 => "Monsour H&#46;"
                            6 => "Martin P&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(15)00349-9"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26456905"
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                      "titulo" => "Safety&#44; and anti- viral efficacy and pharma-cokinetics &#40;PK&#41; of sofosbuvir &#40;SOF&#41; in patients with severe renal impairment&#46; AASLD 2014"
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                            0 => "Gane E&#46;J&#46;"
                            1 => "Robson R&#46;A&#46;"
                            2 => "Bonacini M&#46;"
                            3 => "Maliakkal B&#46;"
                            4 => "Kirby B&#46;"
                            5 => "Liu L&#46;"
                            6 => "Sajvani K&#46;"
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                    ]
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                        "link" => array:1 [
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                      "titulo" => "Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function&#58; real-world experience from HCV-target&#46; EASL 2015"
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                            1 => "Koraishy F&#46;M&#46;"
                            2 => "Sise M&#46;"
                            3 => "Lim J&#46;K&#46;"
                            4 => "Schmidt M&#46;"
                            5 => "Chung R&#46;T&#46;"
                            6 => "Liapakis D&#46;R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
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                        "paginaInicial" => "S267"
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                      "titulo" => "Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection"
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                      "doi" => "10.1016/j.clinthera.2014.12.012"
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                        "tituloSerie" => "Clin Ther"
                        "fecha" => "2015"
                        "volumen" => "37"
                        "paginaInicial" => "243"
                        "paginaFinal" => "267"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25601269"
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                    0 => array:2 [
                      "titulo" => "Randomized comparison of daclatasvir &#43; asunaprevir versus telaprevir &#43; peginterferon&#47;ribavirin in Japanese hepatitis C virus patients"
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                            1 => "Suzuki F&#46;"
                            2 => "Suzuki Y&#46;"
                            3 => "Toyota J&#46;"
                            4 => "Karino Y&#46;"
                            5 => "Chayama K&#46;"
                            6 => "Kawakami Y&#46;"
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                      "doi" => "10.1111/jgh.13349"
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                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "2016"
                        "volumen" => "31"
                        "paginaInicial" => "14"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26990906"
                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "Review article&#58; the efficacy and safety of daclatasvir in the treatment of chronic hepatitis C virus infection"
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                        "tituloSerie" => "Aliment Pharmacol Ther"
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                        "paginaInicial" => "258"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26014906"
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                          "etal" => false
                          "autores" => array:4 [
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                            2 => "Ariello M&#46;"
                            3 => "Mastrolia M&#46;"
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                        "tituloSerie" => "Gut"
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                        "paginaInicial" => "585"
                        "paginaFinal" => "586"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16531544"
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                      "titulo" => "Insulin resistance predicts rapid virological response in non-diabetic&#44; non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus rib-avirin"
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Article information

ISSN: 16652681
Original language: English

DOI:10.5604/16652681.1226817

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	18	0	18
2024 October	52	3	55
2024 September	16	9	25
2024 August	18	2	20
2024 July	14	6	20
2024 June	23	4	27
2024 May	27	3	30
2024 April	16	6	22
2024 March	18	1	19
2024 February	20	6	26
2024 January	16	3	19
2023 December	10	8	18
2023 November	11	5	16
2023 October	21	4	25
2023 September	13	6	19
2023 August	20	5	25
2023 July	17	2	19
2023 June	4	1	5
2023 May	26	4	30
2023 April	46	2	48
2023 March	35	2	37
2023 February	28	2	30
2023 January	14	3	17
2022 December	18	9	27
2022 November	15	6	21
2022 October	17	10	27
2022 September	24	7	31
2022 August	17	5	22
2022 July	14	6	20
2022 June	14	6	20
2022 May	22	13	35
2022 April	19	9	28
2022 March	25	8	33
2022 February	20	7	27
2022 January	52	6	58
2021 December	27	7	34
2021 November	17	6	23
2021 October	35	12	47
2021 September	29	6	35
2021 August	39	8	47
2021 July	14	10	24
2021 June	14	9	23
2021 May	25	6	31
2021 April	96	23	119
2021 March	32	9	41
2021 February	21	10	31
2021 January	15	18	33
2020 December	12	9	21
2020 November	10	6	16
2020 October	12	4	16
2020 September	11	7	18
2020 August	18	12	30
2020 July	9	6	15
2020 June	7	8	15
2020 May	10	4	14
2020 April	2	2	4
2020 March	5	3	8
2020 February	8	6	14
2020 January	9	5	14
2019 December	9	5	14
2019 November	2	2	4
2019 October	1	2	3
2019 September	2	2	4
2019 August	3	2	5
2019 July	2	3	5
2019 June	7	9	16
2019 May	2	4	6

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