Peginterferon alpha-2b plus ribavirin for chronic hepatitis C virus mixed genotype infection
Ching-Chung Lin*,†,‡, Chia-Hsien Wu||, Huan-Lin Chen||, I-Tsung Lin||, Shen-Yung Wang*,‡,§, Tsang-En Wang*,†,‡, Horng-Yuan Wang*,†,‡, Shou-Chuan Shih*,†,‡, Ming-Jong Bair||,¶,**,
Corresponding author
* Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
† Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
‡ Mackay Medical College, New Taipei City, Taiwan
§ Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taitung, Taiwan
|| Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan
¶ Department of Nursing, Meiho University, Pingtung, Taiwan
** Department of Applied Science, National Taitung University, Taitung, Taiwan
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Del Campo, Lourdes Rojas, José R. García-Lozano, Ricard Solá, Raúl Andrade, José A. Pons, José M. Navarro, José L. Calleja, María Buti, María F. González-Escribano, Xavier Forns, Moisés Diago, Javier García-Samaniego, Manuel Romero-Gómez" "autores" => array:15 [ 0 => array:2 [ "nombre" => "Javier" "apellidos" => "Ampuero" ] 1 => array:2 [ "nombre" => "José A. Del" "apellidos" => "Campo" ] 2 => array:2 [ "nombre" => "Lourdes" "apellidos" => "Rojas" ] 3 => array:2 [ "nombre" => "José R." "apellidos" => "García-Lozano" ] 4 => array:2 [ "nombre" => "Ricard" "apellidos" => "Solá" ] 5 => array:2 [ "nombre" => "Raúl" "apellidos" => "Andrade" ] 6 => array:2 [ "nombre" => "José A." "apellidos" => "Pons" ] 7 => array:2 [ "nombre" => "José M." "apellidos" => "Navarro" ] 8 => array:2 [ "nombre" => "José L." "apellidos" => "Calleja" ] 9 => array:2 [ "nombre" => "María" "apellidos" => "Buti" ] 10 => array:2 [ "nombre" => "María F." "apellidos" => "González-Escribano" ] 11 => array:2 [ "nombre" => "Xavier" "apellidos" => "Forns" ] 12 => array:2 [ "nombre" => "Moisés" "apellidos" => "Diago" ] 13 => array:2 [ "nombre" => "Javier" "apellidos" => "García-Samaniego" ] 14 => array:3 [ "preGrado" => "M.D., Ph.D." "nombre" => "Manuel" "apellidos" => "Romero-Gómez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308427?idApp=UINPBA00004N" "url" => "/16652681/0000001300000004/v1_201906020859/S1665268119308427/v1_201906020859/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119308403" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)30840-3" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "70596" "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. 2014;13:340-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 104 "formatos" => array:3 [ "EPUB" => 17 "HTML" => 56 "PDF" => 31 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Long term changes in liver histology following treatment of chronic hepatitis C virus" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "340" "paginaFinal" => "349" ] ] "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" => 294 "Ancho" => 1049 "Tamanyo" => 37748 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Percentage of patients with varying degrees of fibrosis on the second liver biopsy compared to the initial liver biopsy. Patients either deferred treatment (No Tx) or received interferon therapy but failed to achieve a SVR (No SVR). All patients were followed for a minimum of 5 years before they underwent repeat liver biopsy. <span class="elsevierStyleBold">A.</span> Patients with no fibrosis on the initial liver biopsy. <span class="elsevierStyleBold">B.</span> Patients with portal fibrosis on the initial liver biopsy.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mitchell L. Shiffman, Richard K. Sterling, Melissa Contos, Sarah Hubbard, April Long, Velimir A. Luketic, R. Todd Stravitz, Michael Fuchs, Arun J. Sanyal" "autores" => array:9 [ 0 => array:3 [ "preGrado" => "M.D." "nombre" => "Mitchell L." "apellidos" => "Shiffman" ] 1 => array:2 [ "nombre" => "Richard K." "apellidos" => "Sterling" ] 2 => array:2 [ "nombre" => "Melissa" "apellidos" => "Contos" ] 3 => array:2 [ "nombre" => "Sarah" "apellidos" => "Hubbard" ] 4 => array:2 [ "nombre" => "April" "apellidos" => "Long" ] 5 => array:2 [ "nombre" => "Velimir A." "apellidos" => "Luketic" ] 6 => array:2 [ "nombre" => "R. Todd" "apellidos" => "Stravitz" ] 7 => array:2 [ "nombre" => "Michael" "apellidos" => "Fuchs" ] 8 => array:2 [ "nombre" => "Arun J." "apellidos" => "Sanyal" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308403?idApp=UINPBA00004N" "url" => "/16652681/0000001300000004/v1_201906020859/S1665268119308403/v1_201906020859/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Peginterferon alpha-2b plus ribavirin for chronic hepatitis C virus mixed genotype infection" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "350" "paginaFinal" => "355" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ching-Chung Lin, Chia-Hsien Wu, Huan-Lin Chen, I-Tsung Lin, Shen-Yung Wang, Tsang-En Wang, Horng-Yuan Wang, Shou-Chuan Shih, Ming-Jong Bair" "autores" => array:9 [ 0 => array:3 [ "nombre" => "Ching-Chung" "apellidos" => "Lin" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span 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"Shou-Chuan" "apellidos" => "Shih" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">‡</span>" "identificador" => "aff0015" ] ] ] 8 => array:5 [ "preGrado" => "M.D." "nombre" => "Ming-Jong" "apellidos" => "Bair" "email" => array:1 [ 0 => "a5963@ttms.mmh.org.tw" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">||</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¶</span>" "identificador" => "aff0030" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff0035" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan" "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan" "etiqueta" => "†" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Mackay Medical College, New Taipei City, Taiwan" "etiqueta" => "‡" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taitung, Taiwan" "etiqueta" => "§" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan" "etiqueta" => "||" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Department of Nursing, Meiho University, Pingtung, Taiwan" "etiqueta" => "¶" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Department of Applied Science, National Taitung University, Taitung, Taiwan" "etiqueta" => "**" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "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" => 290 "Ancho" => 490 "Tamanyo" => 31195 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">The sustained virologie response rate of patients with mixed genotype 1 + 2 (74%) fell between that of patients with genotype 1 (56%) and genotype 2 (84%).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Despite widespread treatment, hepatitis C deaths are increasing, mostly due to inadequate detection and treatment.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This is true even in developed countries. Accurate hepatitis C virus (HCV) geno-typing is very important for determining optimal strategies and for predicting or estimating the response rate after antiviral treatment.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">HCV can be classified into six major genotypes and numerous subtypes.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The distribution of HCV genotypes varies by geographical location and groups at risk for infection in areas where genotype 1 and genotype 2 are distributed globally, including Taiwan.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">In some special groups, hepatitis C co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) is an important issue. While the treatment policy is well known, less is known about treating the individual with mixed infection, including those with two or more HCV genotypes. In some HCV-infected patients, more than one genotype can be detected (mixed genotype infection).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Recently, an HCV subtyping assay was developed; this assay uses a reliable polymerase chain reaction method to identify individual mixed genotype HCV infection.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The global reported incidence of mixed genotype infection in chronic hepatitis C varies from 5% to 22%.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">We conducted a retrospective cohort study in our clinical practice to evaluate the role of HCV mixed genotype 1 + 2 on the treatment response to 24 weeks of peginterferon/ribavirin compared with HCV genotype 1 or HCV genotype 2. The aim of this study was to investigate the virological response during treatment among these three groups.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Study design and participants</span><p id="p0025" class="elsevierStylePara elsevierViewall">This retrospective cohort study was approved by the Ethics Committee of Mackay Memorial Hospital in Taitung’ Taiwan. We collected data from patients with chronic hepatitis C who were treated at hepatology clinics at Taitung Mackay Memorial Hospital from November 2009 to April 2012. These patients were all treated according to Taiwan National Health Insurance clinical practice guidelines (seropositive for HCV antibodies and HCV RNA, and serum alanine-imunotransferase, or ALT, above 40 IU/L). Patients were eligible for the study if they were 20 years of age or older and had naïve chronic HCV infection treated with peginterferon alpha-2b and ribavirin. The recruited patients had one of the following genotypes: genotype 1, genotype 2, and mixed genotype 1 + 2. The treatment course was 24 weeks of peginterferon alpha-2b (1.5 ug/kg/week) plus weight-based ribavirin (800 mg for those weighing < 65 kg; 1,000 mg for those weighing 65 to 80 kg; and 1,200 mg for patients weighing > 80 kg). The treatment duration was according to the Bureau of National Health Insurance in Taiwan which is reimbursing HCV treatment using 24-week combination therapy for all genotypes. The dosages of peginterferon and ribavirin were modified according to the guidelines provided by the drugs’ manufacturers.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Assessment of efficacy</span><p id="p0030" class="elsevierStylePara elsevierViewall">A rapid virological response (RVR) was defined as failure to detect HCV RNA at 4 weeks of treatment using a sensitive polymerase chain reaction (PCR)-based quantitative analysis. An early virological response (EVR) was defined as undetectable HCV RNA or at least a 2-log (10) decrease from baseline level of the serum HCV RNA at week 12 of treatment. An end of treatment virological response (EOT-R) was defined as undetectable HCV RNA at the end of 24 weeks of treatment. A sustained virological response (SVR) was defined as serum HCV RNA being undetectable 24 weeks after cessation of treatment. Those who did not have available data to assess SVR were considered to have failed to achieve SVR.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Laboratory tests/Quantitative and genotyping tests of HCV RNA</span><p id="p0035" class="elsevierStylePara elsevierViewall">All treated patients had biweekly outpatient visits during the first month, and then monthly visits during the rest of the treatment and follow-up period. Clinical socio-demographic information, including age, gender and weight, was collected, and a medical history that included accompanying disease and any treatment side effects, was taken. Blood biochemistry was performed at enrollment included serum anti-HCV, serum HCV RNA, hepatitis B virus surface antigen (HBs-Ag), hemoglobin, aspartate aminotransferase (AST), ALT, and alpha-fetoprotein (AFP), as well as white blood cell and platelet counts. To test for liver tumor and cirrhosis, abdominal ultrasound was performed for all patients every 6 months. HCV RNA was measured by Roche COBAS®Amplicor PCR assay (Roche Molecular Diagnostics, Basel, Switzerland), with the lower limit of detection and quantitation of 15 IU/mL. HCV genotyping was performed by primer-specific PCR as previously described by Simmonds.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The genotyping was further confirmed by direct PCR deep-sequencing using an ABI 3730 sequencer (CD Genomics, Shirley, NY, USA).</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Statistical analysis</span><p id="p0040" class="elsevierStylePara elsevierViewall">All patients who received at least one dose of medication were included in all efficacy analyses. The data of categorical variables were compared using chi-square test including odds ratios (ORs) and respective 95% confidence intervals for the association of SVR with each category of patient’s characteristics; and continuous variables were compared among the three groups using one-way analysis of variance (ANOVA). The statistical analyses were performed with an SPSS 12.0 statistical package (SPSS, Chicago, IL, USA). Missing data were treated by using the SPSS missing value options. All statistical analyses were based on two-sided hypothesis tests with a significance level of p < 0.05.</p></span></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Results</span><p id="p0045" class="elsevierStylePara elsevierViewall">There were 204 HCV patients assigned to treat with peginterferon and ribavirin, the percentage of HCV genotypes and subtypes analysis were genotype 1 (48.1%), genotype 2 (32.3%), genotype 1 + 2 (15.6%), genotype 6 (3.4%), and unclassified (0.5%), respectively. Those patients whose age below 20, HCV treatment relapse cases, drug with peginterferon alfa-2a, genotype 6 or unclassified were excluded. There were 150 naïve, adult chronic hepatitis C patients treated with peginterferon alpha-2b plus ribavirin included in this study. These patients were divided into 3 groups by HCV genotypes (genotype 1, genotype 2 and mixed genotype 1 + 2). The completion rate of treatment in those with genotype 1 was 83.8%, compared with 92.7% for those with genotype 2 and 77.8% for those with mixed genotype 1 + 2 (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>). The average completion of treatment rate was 85%.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall">The three study groups had similar demographic and clinical characteristics; including gender, mean age, mean body weight, baseline hemoglobin levels, and baseline white blood cell and platelet counts (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>). The baseline mean HCV RNA serum level was high in these three groups: 2.2 ~ 4.7 x 10<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> IU/ mL. There were no significant differences among the 3 groups in baseline ALT and AST. The percentage of liver cirrhosis in the mixed genotype 1 + 2 group (22%) was higher than among that in the genotype 1 group (14.7%) and the genotype 2 group (7.3%), but this was not statistically significant (p = 0.16).</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0055" class="elsevierStylePara elsevierViewall">In contrast, there were significant differences in RVR rate among the 3 groups (p = 0.013). The RVR rate in the genotype 1 group was 64.7%, 85.5% in the genotype 2 group, and 85.2% in the mixed genotype 1 + 2 group. The sustained virological response (SVR) rate was 55.9% in the genotype 1 group, 83.6% in the genotype 2 group, and 74.1% in the mixed genotype 1 + 2 group. There was a significant statistical difference in SVR rate between genotype 1 and genotype 2 groups (p = 0.001). The SVR rate of mixed genotype 1 + 2 (74%) fell between that of the patients in genotype 1 and genotype 2 groups (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>, <a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>).</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0060" class="elsevierStylePara elsevierViewall">Regarding results of virological response, the sustained virological response (SVR) rate according to patients who received at least one dose of the study medication, the odds ratios according to patient’s characters, there was no significant difference (<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>).</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Discussion</span><p id="p0065" class="elsevierStylePara elsevierViewall">According to previous literature, the single nucleotide polymorphisms near the interleukin-28B (IL28B) gene is significantly associated with response to Peg-IFN and ribavirin for patients with chronic genotype 1 HCV infection.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> These variations in the IL28B gene correlated with HCV viral clearance and SVR which may explain the different SVR rates among Asians, Europeans and African-Americans. Asian patients had the highest frequency of the advantageous allele in the gene for IL28B, with up to 88% of Taiwanese patients with chronic hepatitis C having the rs8099917 TT genotype which has been shown to be an important predictor of response.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Recently, the role of IL28B genotyping is particularly relevant as direct-acting antiviral agents (DAA) are more expensive and carry a higher risk for anemia and other drug-related side effects, while decision making based on IL28B genotype may permit non-DAA-based treatment algorithms.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">Blatt, <span class="elsevierStyleItalic">et al</span>. reported that patients infected with HCV genotype 1 and mixed genotypes had significantly higher serum HCV RNA concentrations when compared with patients with genotype 2 and 3.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In our study, the baseline HCV RNA serum level of patients with mixed genotype 1 + 2 was higher than that of patients with genotype 2, but this was not statistically significant. The percentage of liver cirrhosis in the mixed HCV genotype 1 + 2 group was about 22% that was higher than in the genotype 2 group (7.3%); although the difference is not statistically significant, but it should be appropriately valued and considering that mixed HCV genotype infection might have an increased prevalence of liver cirrhosis.</p><p id="p0075" class="elsevierStylePara elsevierViewall">Currently the standard treatment course for chronic hepatitis C is 48 weeks of pegylated interferon, with the addition of ribavirin for HCV genotype 1, and 24 weeks of treatment for patients with HCV genotype 2.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Yu, <span class="elsevierStyleItalic">et al</span>. reported that the SVR rate in naïve Taiwanese patients treated with 24-week course peginterferon/ribavirin was around 50%, and 90% in HCV genotypes 1 and 2 patients.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In this study, we found that the sustained virological response rate among patients who received at least one dose of the study medication was 74.1% among those in the mixed genotype 1 + 2 group, 55.9% in the genotype 1 group, and 83.6% in the genotype 2 group. However, in the best scenario, among patients who completed treatment, the SVR rate of the mixed genotype 1 + 2 group (95.2%) was similar to that of the genotype 2 group (90.2%). Which dominant variant in HCV mixed genotype 1 + 2 is worth evaluating, since the viral dynamics are different between genotype 1 and genotype 2?<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">In Taiwan, both 24 and 48 weeks of dual therapy can achieve a high SVR rate (> 96%) in patients with HCV genotype 1, with low viral load and an RVR,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> so optimizing HCV therapy in patients with HCV genotype 1 in some endemic areas is important.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Determining the optimal treatment course for patients with mixed genotype infections is also an important issue and must take into consideration different subtypes in different geographic areas. In this study, we used pegylated interferon alpha-2b with the addition of ribavirin for 24 weeks to treat mixed HCV genotype 1 + 2 infections, and as a result achieved a 74.1% SVR rate.</p><p id="p0085" class="elsevierStylePara elsevierViewall">Real-world data from HCV treatment in Australia reported that only 75% (414/550) of patients completed their treatment, 6.4% because of an adverse event. For 4.7%, the reason given for stopping treatment was “the patient’s decision”.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In our study, the completion rate was 85%. Devising strategies to increase the treatment completion rate is very important, and includes developing infrastructure support and expanding treatment services to the broader HCV-infected community.</p><p id="p0090" class="elsevierStylePara elsevierViewall">Our study had numerous limitations. First, it was a retrospective cohort study and included only a small sample of patients with mixed genotype 1 + 2 infections. Second, tests for IL-28B genotype are not currently available under Taiwanese national health insurance. Having an IL-28B genotype could predict a pretreatment response and an SVR to an abbreviated 24-week course of peginterferon/ribavirin in HCV-1 patients who did not achieve RVR and had high baseline viral loads.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Conclusions</span><p id="p0095" class="elsevierStylePara elsevierViewall">Using peginterferon alpha-2b plus ribavirin for 24 weeks to treat mixed patients with HCV genotype 1 + 2 achieved a 74.1% SVR rate; this treatment efficacy was not inferior to patients with HCV genotype 1.</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Funding</span><p id="p0100" class="elsevierStylePara elsevierViewall">Mackay Memorial Hospital, Taitung, Taiwan.</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Competing Interests</span><p id="p0105" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests.</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Authors’ Contributions</span><p id="p0110" class="elsevierStylePara elsevierViewall">Ching-Chung Lin, Shen-Yung Wang and Ming-Jong Bair constructed the study design, performed the data analysis, and wrote the article.</p><p id="p0115" class="elsevierStylePara elsevierViewall">Chia-Hsien Wu, Huan-Lin Chen, I-Tsung Lin, Tsang-En Wang, Horng-Yuan Wang, Shou-Chuan Shih participated in the study design and literature review and revision of the manuscript.</p><p id="p0120" class="elsevierStylePara elsevierViewall">All authors read and approved the final manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1199016" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1117456" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Study design and participants" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Assessment of efficacy" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Laboratory tests/Quantitative and genotyping tests of HCV RNA" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "s0040" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "s0045" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "s0050" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "s0055" "titulo" => "Competing Interests" ] 9 => array:2 [ "identificador" => "s0060" "titulo" => "Authors’ Contributions" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-12-15" "fechaAceptado" => "2014-02-21" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1117456" "palabras" => array:3 [ 0 => "Interferon" 1 => "Ribavirin" 2 => "Mixed infection" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Background and aim.</span> The treatment efficacy of peginterferon plus ribavirin for patients with HCV genotype 1 is inferior to that in patients with HCV genotype 2, but the efficacy among patients with mixed HCV genotype 1 + 2 is less clear. We compared the treatment outcome of peginterferon alpha-2b plus ribavirin among naïve chronic hepatitis C patients in Taiwan with HCV genotype 1 and 2, and mixed genotype 1 + 2.</p><p id="sp12045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods.</span> In this retrospective cohort study, 150 patients were treated with peginterferon alpha-2b once weekly, plus ribavirin, for 24 weeks. The endpoint was sustained virological response after receiving at least one dose of the study medication.</p><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results.</span> There were no differences in clinical characteristics among the 3 groups. There were significant differences in rapid virological response rate between patients with genotype 1 and genotype 2 (64.7 <span class="elsevierStyleItalic">vs.</span> 85.5%, respectively; p < 0.05) and a sustained virological response rate (55.9 <span class="elsevierStyleItalic">vs.</span> 83.6%, respectively; p = 0.001). The rapid virological response rate differed between the genotype 1 and mixed genotype 1 + 2 groups (64.7 <span class="elsevierStyleItalic">vs.</span> 85.2%, respectively; p < 0.05), but the sustained virological response rate was similar (55.9 <span class="elsevierStyleItalic">vs.</span> 74.1%; p = 0.101). <span class="elsevierStyleBold">Conclusions.</span> Using peginterferon alpha-2b plus ribavirin for 24 weeks to treat patients with HCV genotype 1 + 2 achieved a 74.1% sustained virological response rate; the treatment efficacy was not inferior to patients with HCV genotype 1, but the percentage of liver cirrhosis in mixed genotype 1 + 2 group was higher to 22%, it is worth to be appropriately valued and studied.</p></span>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 555 "Ancho" => 864 "Tamanyo" => 64253 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">This diagram shows the course of all patients evaluated for hepatitis C treatment with peginterferon alpha-2b and ribavirin. It also indicates the number of patients who refused treatment, had adverse events, or prematurely stopped treatment for personal reasons.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 290 "Ancho" => 490 "Tamanyo" => 31195 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">The sustained virologie response rate of patients with mixed genotype 1 + 2 (74%) fell between that of patients with genotype 1 (56%) and genotype 2 (84%).</p>" ] ] 2 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "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="" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 1 (n = 68) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 2 (n = 55) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 1 + 2 (n = 27) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value \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">Male, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (54.4%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (40%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (48.1%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.9 ± 11.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.5 ± 10.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.6 ± 11.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.69 \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">Weight, kg \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.5 ± 15.5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68.7 ± 12.9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66.4 ± 11.3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.78 \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">Base HCV RNA, mean ± SD (x10<span class="elsevierStyleSup">6</span> 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.6 ± 8.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.2 ± 3.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7 ± 7.9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.10 \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">Base ALT, mean ± SD (IU/L) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">121.9 ± 85.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">121.2 ± 75.9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">117.5 ± 101.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98 \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">Base AST, mean ± SD (IU/L) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98.3 ± 80.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.0 ± 40.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106.8 ± 84.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.52 \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">Base Hb (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.9 ± 1.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.8 ± 1.3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.0 ± 1.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.86 \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">Base WBC μL) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5091 ± 1881 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5327 ± 1734 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5523 ± 2305 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 \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">Base PLT (x10<span class="elsevierStyleSup">3</span>/μL) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">166.2 ± 97.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">165.4 ± 57.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">145.9 ± 63.5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.60 \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">Liver cirrhosis, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (14.7%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (7.3%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (22.2%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047788.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical characters of naïve HCV treatment patients according to genotype.</p>" ] ] 3 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">RVR: rapid virological response. EVR: early virological response. EOTVR: end of treatment virological response. SVR: sustained virological response. P: <span class="elsevierStyleItalic">p</span> value.</p>" "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="" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 1 (n = 68) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 2 (n = 55) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genotype 1+2 (n = 27) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P \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">RVR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (64.7%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 (85.5%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (85.2%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.013 \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">EVR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (85.3%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (94.5%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (92.6%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.208 \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">EOTVR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (79.4%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (89.1%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (92.6%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.160 \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">SVR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (55.9%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (83.6%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (74.1%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047787.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Virological response rate according to patients who receive at least one dose of the study medication.</p>" ] ] 4 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0010" class="elsevierStyleSimplePara elsevierViewall">n (%): patient number and SVR percentage. OR: odds ratio.</p>" "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 " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency of patients with SVR</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th></tr><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">OR (95% CI) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p-value \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">Male, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 (70.8%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.87 (0.44-1.75) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.70 \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">Age >55, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 (70.1%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.96 (0.68-1.36) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 \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">BW > 80 kg, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (65.4%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.20 (0.58-2.48) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \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">Baseline HCV Viral load >4 ×10<span class="elsevierStyleSup">5</span> IU/mL, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (64.4%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.76 (0.80-3.86) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \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">Liver cirrhosis, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (55.0%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.85 (0.82-4.16) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047786.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Sustained virological response rate and odds ratio according to patients who received at least one dose of the study medication.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Viral hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Poynard T." 1 => "Yuen M.F." 2 => "Ratziu V." 3 => "Lai C.L." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "362" "paginaInicial" => "2095" "paginaFinal" => "2100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14697814" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 7 | 1 | 8 |
| 2024 September | 6 | 2 | 8 |
| 2024 August | 11 | 2 | 13 |
| 2024 July | 6 | 1 | 7 |
| 2024 June | 4 | 0 | 4 |
| 2024 May | 10 | 1 | 11 |
| 2024 April | 14 | 7 | 21 |
| 2024 March | 9 | 3 | 12 |
| 2024 February | 9 | 4 | 13 |
| 2024 January | 7 | 2 | 9 |
| 2023 December | 6 | 11 | 17 |
| 2023 November | 2 | 1 | 3 |
| 2023 October | 5 | 5 | 10 |
| 2023 September | 7 | 4 | 11 |
| 2023 August | 10 | 1 | 11 |
| 2023 July | 11 | 4 | 15 |
| 2023 June | 7 | 3 | 10 |
| 2023 May | 21 | 4 | 25 |
| 2023 April | 24 | 0 | 24 |
| 2023 March | 13 | 0 | 13 |
| 2023 February | 5 | 7 | 12 |
| 2023 January | 4 | 3 | 7 |
| 2022 December | 8 | 3 | 11 |
| 2022 November | 6 | 3 | 9 |
| 2022 October | 7 | 4 | 11 |
| 2022 September | 5 | 7 | 12 |
| 2022 August | 7 | 6 | 13 |
| 2022 July | 7 | 8 | 15 |
| 2022 June | 5 | 4 | 9 |
| 2022 May | 11 | 5 | 16 |
| 2022 April | 10 | 9 | 19 |
| 2022 March | 4 | 8 | 12 |
| 2022 February | 14 | 3 | 17 |
| 2022 January | 34 | 3 | 37 |
| 2021 December | 39 | 11 | 50 |
| 2021 November | 21 | 7 | 28 |
| 2021 October | 44 | 10 | 54 |
| 2021 September | 21 | 7 | 28 |
| 2021 August | 14 | 12 | 26 |
| 2021 July | 9 | 4 | 13 |
| 2021 June | 3 | 6 | 9 |
| 2021 May | 13 | 6 | 19 |
| 2021 April | 40 | 24 | 64 |
| 2021 March | 16 | 6 | 22 |
| 2021 February | 4 | 7 | 11 |
| 2021 January | 8 | 9 | 17 |
| 2020 December | 4 | 7 | 11 |
| 2020 November | 5 | 7 | 12 |
| 2020 October | 12 | 4 | 16 |
| 2020 September | 9 | 6 | 15 |
| 2020 August | 9 | 3 | 12 |
| 2020 July | 5 | 1 | 6 |
| 2020 June | 5 | 2 | 7 |
| 2020 May | 3 | 4 | 7 |
| 2020 April | 4 | 3 | 7 |
| 2020 March | 6 | 1 | 7 |
| 2020 February | 2 | 1 | 3 |
| 2020 January | 2 | 3 | 5 |
| 2019 December | 6 | 4 | 10 |
| 2019 November | 4 | 2 | 6 |
| 2019 October | 0 | 1 | 1 |
| 2019 September | 1 | 0 | 1 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 1 | 1 | 2 |
| 2019 June | 3 | 4 | 7 |
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