Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia | Gastroenterología y Hepatología (English Edition)

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"etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Jésica" "apellidos" => "Ugalde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Montserrat" "apellidos" => "Laguno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "María" "apellidos" => "Martínez-Rebollar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Raquel" "apellidos" => "Ojeda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Marta" "apellidos" => "Arias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Lida" "apellidos" => "Rodas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Florencia" "apellidos" => "Rossi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Laura-Patricia" "apellidos" => "Llovet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 10 => array:3 [ "nombre" => "Leonardo Nicolás" "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 11 => array:3 [ "nombre" => "Josep" "apellidos" => "Mallolas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 12 => array:4 [ "nombre" => "Maria-Carlota" "apellidos" => "Londoño" "email" => array:1 [ 0 => "mlondono@clinic.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eliminación de la hepatitis C de una unidad de hemodiálisis e impacto del tratamiento en el control de la anemia" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1339 "Ancho" => 2167 "Tamanyo" => 147985 ] ] "descripcion" => array:1 [ "en" => "Evolution of hematological parameters after treatment discontinuation. Data were analyzed using one-way repeated measures ANOVA. EOT: End of therapy, SVR12: 12 weeks after treatment discontinuation, SVR24: 24 weeks after treatment discontinuation, SVR48: 48 weeks after treatment discontinuation." ] ] ] "textoCompleto" => "IntroductionRecent data estimates that the global prevalence of hepatitis C virus (HCV) infection is around 1.6% with a viremic prevalence of 1.1%. This corresponds to 80 million people infected with HCV worldwide.<a class="elsevierStyleCrossRef" href="#bib0150">1</a> Hepatitis C infection is a common cause of liver disease in patients with chronic kidney disease (CKD) who receive long-term renal replacement therapy and it is associated with an increased risk of death, hospitalization, anemia and a reduced quality of life.<a class="elsevierStyleCrossRefs" href="#bib0155">2–4</a> Dialysis Outcomes and Practice Pattern Study (DOPPS) showed a prevalence of HCV infection in hemodialysis (HD) patients of 7.5%.<a class="elsevierStyleCrossRef" href="#bib0165">4</a> However, some studies suggest that the prevalence may be underestimated due to the presence of occult HCV infection, defined as the presence of HCV-RNA in hepatocytes and absence of anti-HCV antibodies in routine serological tests.<a class="elsevierStyleCrossRef" href="#bib0160">3</a> The risk of infection varies according to the type of renal replacement therapy (being higher in patients treated with maintenance HD), the time on HD, and the prevalence of HCV infection in the specific dialysis unit.<a class="elsevierStyleCrossRefs" href="#bib0160">3,5</a>Chronic HCV infection in HD patients is associated with an increase in mortality rate not only due to liver causes, but also related with cardiovascular disease, anemia, hepatitis B virus (HBV) or human immunodeficiency virus (HIV) coinfection, and essential mixed cryoglobulinemia.<a class="elsevierStyleCrossRefs" href="#bib0160">3,5–7</a> In addition, HCV infection contributes to an increase morbidity and mortality after kidney transplantation. Indeed, hepatitis C positive kidney transplantation recipients are at increased risk of developing de novo and recurrent membranous nephropathy, membranoproliferative glomerulonephritis and transplant glomerulopathy.<a class="elsevierStyleCrossRef" href="#bib0185">8</a>Anemia is a common complication of patients with chronic kidney disease. Symptoms generally occur when hemoglobin levels are below 10g/dL, but can be more severe when kidney function worsens.<a class="elsevierStyleCrossRef" href="#bib0190">9</a> More importantly, anemia has been associated with an increased mortality and a reduced quality of life.<a class="elsevierStyleCrossRef" href="#bib0195">10</a> There is a scarcity of information on the role of HCV and CKD-related anemia, but there are some data showing that HCV positive patients have low hemoglobin levels and higher EPO dose requirements compared to uninfected patients.<a class="elsevierStyleCrossRef" href="#bib0200">11</a> However, the impact of HCV infection elimination on the control of anemia is unknown.New direct-acting antivirals (DAAs) have demonstrated their efficacy and safety on the treatment of HCV in patients with advanced CKD on HD, with sustained virological response (SVR) rates ranging between 90% and 100% and excellent safety data.<a class="elsevierStyleCrossRefs" href="#bib0205">12–15</a> Therefore, we hypothesized that HCV infection can be safely eliminated from HD units in order to avoid the risk of new HCV infections among HD patients and staff and that HCV elimination could impact on renal function and CKD-related complications. The aims of the study were to determine the success in eliminating HCV infection from our dialysis unit after DAAs therapy in all patients on HD, and to evaluate the impact of therapy on clinical and analytical outcomes.Material and methodsStudy design and antiviral therapyThis is a prospective, observational, single center study, in which all HCV-RNA positive patients in our HD unit (at Hospital Clínic Barcelona and its associated dialysis centers) received antiviral therapy with an interferon (IFN)-free regimen within a 3 year period (April 2014 to March 2017). The antiviral regimen was decided by the treating physician based on published guidelines and information available at the time of treatment indication (Asunaprevir [ASV]+Daclatasvir [DCV], Ombitasvir/Paritaprevir/ritonavir with or without Dasabuvir [3D or 2D], Grazoprevir [GZR]/Elbasvir [EBV], or Sofosbuvir [SOF]+DCV). Direct-acting antivirals were administered according to the recommendations of the specific insert packages. The usage and dose of RBV were also decided by the treating physician according to the treatment regimen recommendations and the status of the patient. The duration of therapy was 12 or 24 weeks according to recommendations of the European Association for the Study of the Liver (EASL) guidelines.<a class="elsevierStyleCrossRef" href="#bib0225">16</a> Since the aim of the study was the elimination of HCV infection from HD unit, the presence of significant comorbidities was not considered as a contraindication to receive antiviral therapy. Potential drug–drug interactions were actively investigated and if detected, concomitant medications were modified appropriately.MonitoringFor each patient, data on age, gender, previous comorbidities, time on dialysis, duration of each dialysis session, etiology of CKD, HBV or HIV coinfection, and previous HCV treatments were collected at baseline. Liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl-transpeptidase [GGT], alkaline phosphatase [ALP] and bilirubin), inflammatory markers (C-reactive protein, CRP) and parameters for the control of anemia (hematocrit, hemoglobin, ferritin, transferrin saturation index [TSI], dose of darbepoetin and intravenous iron) were monitored monthly from 3 months before starting antiviral therapy to the end of the follow-up (12 months after treatment discontinuation). Liver stiffness measurements (LSM) were performed at baseline and 3 months after treatment discontinuation. Both determinations were conducted after HD session to avoid the impact of fluid overload on LSM.<a class="elsevierStyleCrossRef" href="#bib0230">17</a>HCV-RNA was measured by quantitative polymerase chain reaction with a lower limit of quantification of 15YIU/L (Versant kPCR Molecular Systems, Siemens Medical Solutions Diagnostics, New York, USA) at baseline and week 4 of antiviral therapy, end of therapy and 12 weeks after treatment discontinuation. Afterwards, HCV-RNA was monitored every 3 months according to local protocol at the HD unit. Sustained virological response (SVR) was considered when HCV-RNA was negative 12 weeks after the end of treatment.Side effects were assessed during treatment and within 12 months of treatment discontinuation. All adverse events referred by the patient were collected. Special attention was given to the development or worsening of anemia (defined as hemoglobin levels<10g/dL). The management of anemia was carried out by correcting the dose of darbepoietin and intravenous iron according to hemoglobin, hematocrit, ferritin, and transferrin saturation index (TSI).<a class="elsevierStyleCrossRef" href="#bib0235">18</a>Statistical analysisContinuous variables are expressed as mean (standard deviation). Categorical variables are expressed as number and percentage. Comparisons between categorical variables were performed by Chi-square test or Fischer test as appropriate. Comparisons between continuous variables were performed by T-test or non-parametric tests. A one-way repeated measures ANOVA was used to determine whether there was a statistical difference between paired analyses. A p value <0.05 was considered significant. Statistical analysis was performed using the statistical SPSS version 23.ResultsEffectiveness and tolerability of antiviral therapyAs shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, 26 (10%) out of the 262 attending our HD unit during the study period were anti-HCV and HCV-RNA positive. During the study period, 4 patients discontinued HD treatment (2 due to kidney transplantation, 1 patient was transfer to another center, and 1 patient died due to hepatocellular carcinoma), and 2 patients did not require antiviral treatment due to spontaneous HCV-RNA negativization. Thus, 20 patients were candidates to receive DAAs treatment.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The characteristics of the 20 treated patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Briefly, 65% were male, with a mean age of 53.6±8.3 years, infected with genotype 1b (60%), and stable on HD over a period of 82±79 months. Twenty percent of patients were non-responders to a previous course of an IFN-based therapy. The dialysis modality was on-line hemodiafiltration with post-dilutional infusion in all patients. Twenty-five percent (n=5) of patients had diabetes mellitus, 40% (n=8) had cirrhosis and 25% (n=5) had other viral coinfections (3 HIV infection, 2 HBV infection). The etiologies of CKD were: glomerulonephritis (n=8, 40%), diabetic nephropathy (n=3, 15%), amyloidosis (n=2, 10%), chronic interstitial nephropathy (n=2, 10%), nephroangiosclerosis (n=1, 5%), obstructive uropathy (n=1, 5%). In the remaining 3 patients (15%) the etiology of CKD was unknown.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The most commonly used DAAs regimen was Ombitasvir, Paritaprevir/ritonavir and Dasabuvir (n=9; 45%). Ribavirin (RBV) was added only in one patient infected with genotype 1a. Interestingly, 3 patients infected with genotypes 2 or 3 received a Sofosbuvir-based combination (off-label). The specific treatment, dose and duration are shown in Supplementary Table 1.At week 4 of therapy, viral load for HCV was undetectable in all patients and all of them achieved SVR. No reinfections were observed in any of the subjects during the follow-up period. After achieving SVR, 3 patients who asked for it were relocated in dialysis shifts for HCV negative patients.Medication was well tolerated with mild side effects in 40% of patients (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). None of these side effects led to treatment discontinuation.Impact of therapy on clinical and analytical outcomesAs expected, SVR was associated with an improvement in liver tests (Supplementary Table 2) and liver stiffness measurement determined at the time of SVR (from 9.7±5.1kPa to 7.5±4.0kPa; p=0.008). C-reactive protein did not change significantly changed during and after DAA therapy (Supplementary Table 2).We observed an improved control of anemia after DAAs treatment (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), with a significant increase hemoglobin and hematocrit levels after the end of treatment (p=0.017 and p=0.048; respectively). This was associated with a tendency toward a decrease in the dose of intravenous iron (p=0.064). There were no significant changes in the dose of darbepoetin and ERI index. In addition, ferritin levels and transferrin saturation index did not significantly changed after treatment discontinuation (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionHere, we showed for the first time that with the new DAAs treatments it is possible to eliminate HCV infection from HD units. Despite the prevalence of HCV in patients on HD having declined significantly in recent years, it is still higher than that of the general population carrying a significant increase in morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0240">19,20</a> The international observational study on the long-term guidelines and results of patients on HD (DOPPS) reviewed 76,689 adult patients between 1996 and 2015.<a class="elsevierStyleCrossRef" href="#bib0165">4</a> The prevalence of HCV infection observed among countries participating in all phases of DOPPS was 14.3% in phase 1 (1996–2001), 10.7% in phase 2 (2002–2004), 8.8% in the phase 3 (2005–2008), 6.8% in phase 4 (2009–2011) and 8.7% in phase 5 (2012–2015). The prevalence of HCV infection in our HD unit, with a mean time in dialysis of 82.0±78.7 months was 10%, which is slightly higher than that observed in DOPPS phase 5.Prior to 2011, standard HCV treatment was based on pegylated interferon (PegINF) or the combination of PegIFN and RBV, which resulted in SVR rates of 40–50%, although their significant adverse effects and low rate of SVR, limited their widespread use. Despite the relatively good results in terms of efficacy in patients on HD treated with PegIFN and RBV,<a class="elsevierStyleCrossRef" href="#bib0250">21</a> the use of this therapy was hampered by the significantly high number of adverse events observed in this subpopulation. A study by our group<a class="elsevierStyleCrossRef" href="#bib0255">22</a> showed that up to 60% of patients on HD treated with an IFN-based therapy early discontinued treatment due to adverse events (including hematological disorders and infections). This explains the low applicability of IFN-based therapies in patients on HD as shown in the DOPPS study, in which only 1.5% of the patients included received antiviral therapy.<a class="elsevierStyleCrossRef" href="#bib0165">4</a>The development of IFN-free therapies with different combinations of DAAs has revolutionized the treatment of patients in HD. There are 3 clinical trials specifically designed to evaluate the safety and efficacy of antiviral therapy in patients with chronic kidney disease stages 4 and 5. The RUBY-1<a class="elsevierStyleCrossRef" href="#bib0205">12</a> trial evaluated the 3D combination with or without RBV in 20 genotype 1-infected patients with CKD stages 4 and 5. Overall, 90% (18 out of the 20 patients) achieved SVR12. Anemia was the most common adverse event. In the second part of the study, 18 genotype 1a and 4 infected patients (normally requiring RBV) received the 3D or 2D combination without RBV and all of them achieved SVR. In the C-SURFER<a class="elsevierStyleCrossRef" href="#bib0210">13</a> study, 224 genotype 1 infected patients were randomly assigned to receive the combination of Grazoprevir and Elbasvir once daily for 12 weeks or placebo (deferred treatment). In the full set analysis, 94% and 95% of patients in the immediate and the deferred treatment groups, respectively, achieved SVR12. More recently, the combination of Glecaprevir and Pibrentasvir administered for 12 weeks to 104 patients infected with different HCV genotypes and CKD stages 4 and 5 achieved an SVR of 100% with excellent safety results.<a class="elsevierStyleCrossRef" href="#bib0215">14</a>Similar to the results of clinical trials or real life cohorts,<a class="elsevierStyleCrossRefs" href="#bib0205">12,23,24</a> we obtained excellent results with the different DAAs combinations administered to our cohort. Most of our patients received the 3D combination for 12 weeks and all of them achieved SVR. Only one patient (genotype 1a) required RBV and prolonged treatment duration (24 weeks) because of the presence cirrhosis. Despite Sofosbuvir is currently not approved for the treatment of patients with a glomerular filtration rate<30ml/min, 3 of our patients (infected with genotype 2 and 3) with no other treatment options received Sofosbuvir in combination with Daclatasvir for 12 or 24 weeks with excellent results in terms of efficacy and safety. This is similar to what has been observed in small series of cases published recently evaluating different combinations of Sofosbuvir-based regimes in which SVR rate ranged between 67% and 100% depending on the dose of Sofosbuvir (standard dose of 400mg per day vs. 400mg every other day or 200mg per day) and the additional drug (RBV vs. other DAA).<a class="elsevierStyleCrossRefs" href="#bib0245">20,25–27</a> More importantly, despite the concerns of using Sofosbuvir in patients on HD due to the potential side effects secondary to GS331007 (principal metabolite of Sofosbuvir) accumulation, we and others did not observe serious adverse events in patients on HD receiving this drug. However, more data are needed to confirm these results and to recommend the widespread use of Sofosbuvir in patients on HD.Interestingly, we observed an improvement in the control of anemia with a significant increase in hemoglobin and hematocrit levels, and a tendency toward a decrease in the dose of intravenous iron during the 12 months after treatment discontinuation. The explanation for this phenomenon is unknown. However, one can speculate that elimination of HCV infection could improve iron metabolism and response to erythropoiesis due to a decrease in systemic inflammation. The role of HCV infection on iron metabolism in patients on HD is controversial. A study by Abdalla et al.,<a class="elsevierStyleCrossRef" href="#bib0200">11</a> showed that HCV positive patients on HD had higher EPO requirement (49.6 vs. 14.4 units/kg/dialysis; p=0.006) and low hemoglobin levels (10.5 vs. 11.2g/dL; p=0.03) as compared to HCV negative patients. However, more recent studies have shown opposite results. For example, Khurana et al.,<a class="elsevierStyleCrossRef" href="#bib0285">28</a> found that HCV positive patients required low EPO dose as compared to HCV negative counterparts (253 vs. 460 units/kg/month) with no significant differences in other parameters. In addition, the number of patients not requiring EPO was significantly higher among HCV positive patients. Since, CKD-related anemia is associated with significant morbidity and mortality; the improvement in the control of anemia could improve cardiovascular risk, long-term survival, and quality of life. Obviously, the limited number of patients included in the study and the short follow-up duration (up to 1 year after treatment discontinuation) preclude us to draw a formal conclusion. However, new studies, with longer follow-up of treated patients, would be interesting to confirm this hypothesis.In order to prevent HCV transmission in HD units, KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend to strictly adhering to infection-control procedures. However, isolation of HCV infected patients or using specifically dedicated machines for these patients is not recommended.<a class="elsevierStyleCrossRef" href="#bib0290">29</a> In our unit, we follow these recommendations but all HCV positive patients are located in dialysis shifts with a specific nurse devoted to their care following the international recommendations to avoid blood-borne pathogens. There is no information on the literature regarding the management of HD patients achieving SVR after antiviral therapy. In our unit viral elimination, at the time of SVR achievement (3 months after the end of therapy) patients are relocated to HCV negative dialysis shift.Our study has several limitations, including the low number of patients enrolled, the absence of patients infected with less frequent genotypes, and the lack of a standardized treatment for all patients due to the rapid evolution of antiviral treatments within the past few years. However, this is a proof of concept that HCV infection can be eliminated from HD units by treating all patients (including patients with severe comorbidities) by a multidisciplinary team of experts in the management of this subpopulation.In conclusion, with the incorporation of new DAAs it is possible to eradicate HCV from dialysis units. The variety of therapeutic possibilities, along with the high efficacy and good tolerance of these drugs allows treating and curing the whole dialysis population. HCV elimination in HD units is a major breakthrough that should allow a zero incidence of hepatitis C infections. Despite further research and validation is required, it appears that HCV elimination is associated, at individual level, to an improvement in the control of anemia.Conflict of interestMCL has received advisory fees from Janssen, Abbvie, Gilead, MSD and BMS. The other authors have declared no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1164412" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1089786" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1164413" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1089785" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and antiviral therapy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Monitoring" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Effectiveness and tolerability of antiviral therapy" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Impact of therapy on clinical and analytical outcomes" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-06-07" "fechaAceptado" => "2018-07-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1089786" "palabras" => array:4 [ 0 => "Elimination" 1 => "Hemodialysis" 2 => "Hepatitis C virus" 3 => "Sustained virologic response" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1089785" "palabras" => array:4 [ 0 => "Eliminación" 1 => "Hemodiálisis" 2 => "Virus de la hepatitis C" 3 => "Respuesta viral sostenida" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionIn the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. Patients and methodsThis is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014–2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. ResultsAll patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. ConclusionHCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEn la época del interferón, el tratamiento del virus de la hepatitis C (VHC) en pacientes en hemodiálisis (HD) se veía limitado por la presencia de efectos adversos relacionados con el tratamiento. Los agentes antivirales directos (AAD) han demostrado ser seguros y eficaces en el tratamiento del VHC en pacientes con insuficiencia renal crónica en hemodiálisis. El objetivo del estudio fue evaluar el éxito en eliminar la infección por VHC de nuestra unidad de diálisis con el uso de AAD, y determinar el impacto clínico y analítico de la curación de la infección. Pacientes y métodosPara ello se realizó un estudio prospectivo de intervención en el Hospital Clinic de Barcelona y su centro de diálisis. Se incluyeron todos los pacientes (n=20) con ARN-VHC positivo que recibieron tratamiento antiviral con AAD durante un periodo de 3 años (2014-2017). Se analizaron los datos de respuesta virológica, efectos adversos y parámetros hematológicos y bioquímicos durante y después del tratamiento. ResultadosTodos los pacientes alcanzaron una respuesta viral sostenida (RVS) y solo una 40% presentaron efectos adversos leves. Ningún paciente presentó reinfección por el VHC y por ello tras un año de seguimiento se consideró la eliminación del VHC de nuestra unidad de diálisis. La RVS se asoció con aumento significativo de la hemoglobina y el hematocrito, y una tendencia a la necesidad de una dosis más baja de suplemento de hierro sin cambios en la dosis de darbepoetina. ConclusiónCon la utilización de AAD, la infección por el VHC puede ser eliminada de forma segura de las unidades de diálisis, previniendo la transmisión de la infección a pacientes y personal sanitario. A corto plazo, la RVS se asoció con una mejoría en el control de la anemia." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following is the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0060" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1537 "Ancho" => 2169 "Tamanyo" => 161501 ] ] "descripcion" => array:1 [ "en" => "Flowchart of the patients with HCV infection detected in the HD unit." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1339 "Ancho" => 2167 "Tamanyo" => 147985 ] ] "descripcion" => array:1 [ "en" => "Evolution of hematological parameters after treatment discontinuation. Data were analyzed using one-way repeated measures ANOVA. EOT: End of therapy, SVR12: 12 weeks after treatment discontinuation, SVR24: 24 weeks after treatment discontinuation, SVR48: 48 weeks after treatment discontinuation." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD: standard deviation." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n=20 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53.6±8.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (65%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cirrhosis, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (40%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Coinfection, n(%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Genotype, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (20%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (60%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous antiviral treatment, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (20%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Current antiviral treatment, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Asunaprevir/Daclatasvir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Grazoprevir/Elbasvir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paritaprevir/Ombitasvir/Dasabuvir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (40%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paritaprevir/Ombitasvir/Dasabuvir/Ribavirin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Simeprevir/Daclatasvir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sofosbuvir/Daclatasvir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adverse effects, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (40%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1987553.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of the patients included in the study." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Data are expressed as median (range). EOT: end of therapy, SVR12: 12 weeks after treatment discontinuation, SVR24: 24 weeks after treatment discontinuation, SVR48: 48 weeks after treatment discontinuation." "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hemoglobin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hematocrit (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EV iron dose (mg/week) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Darbepoetin dose (mcg/week) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ERI IU/week/kg/g Hb \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ferritin (μg/L) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TSI (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">112.9±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36±5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49.9±38.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23±21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.06±7.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">489±301 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25±10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EOT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">110.2±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34±4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57.2±36.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26±21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.44±7.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">305±132 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20±10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">115.9±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35±3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64.6±35.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30±24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.86±7.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">310±147 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22±8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">117±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36±4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.8±31.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24±20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.02±6.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">339±171 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21±7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">117.9±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37±4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43.4±25.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.63±5.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">390±232 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23±9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p-Value<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.048 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.064 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.138 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.128 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.238 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.707 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1987551.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p-Value was determined by one-way repeated measure ANOVA." ] ] ] "descripcion" => array:1 [ "en" => "Hematological parameters during and after treatment discontinuation." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient number \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse event \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arthralgia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heartburn \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diarrhea and pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Headache \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1987552.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Adverse events reported during antiviral therapy." ] ] 5 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 17612 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global epidemiology and genotype distribution of the hepatitis C virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Gower" 1 => "C. Estes" 2 => "S. Blach" 3 => "K. Razavi-Shearer" 4 => "H. Razavi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2014.07.027" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2014" "volumen" => "61" "paginaInicial" => "S45" "paginaFinal" => "S57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25086286" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0155" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K.N. Ly" 1 => "J. Xing" 2 => "R.M. Klevens" 3 => "R.B. Jiles" 4 => "J.W. Ward" 5 => "S.D. Holmberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-156-4-201202210-00004" "Revista" => array:5 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2012" "volumen" => "156" "paginaInicial" => "271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22351712" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0160" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age and gender differences in the relationship between hepatitis C infection and all stages of Chronic kidney disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "W.-C. Li" 1 => "Y.-Y. Lee" 2 => "I.-C. Chen" 3 => "S.-H. Wang" 4 => "C.-T. Hsiao" 5 => "S.-S. 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Original article

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia

Eliminación de la hepatitis C de una unidad de hemodiálisis e impacto del tratamiento en el control de la anemia

Francesc Maduella, Lara Belmara, Jésica Ugaldea, Montserrat Lagunob, María Martínez-Rebollarb, Raquel Ojedaa, Marta Ariasa, Lida Rodasa, Florencia Rossia, Laura-Patricia Llovetc, Leonardo Nicolás Gonzáleza, Josep Mallolasb, Maria-Carlota Londoñoc,

Corresponding author

mlondono@clinic.cat

Corresponding author.

a Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain

b HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain

c Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Recent data estimates that the global prevalence of hepatitis C virus &#40;HCV&#41; infection is around 1&#46;6&#37; with a viremic prevalence of 1&#46;1&#37;&#46; This corresponds to 80 million people infected with HCV worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Hepatitis C infection is a common cause of liver disease in patients with chronic kidney disease &#40;CKD&#41; who receive long-term renal replacement therapy and it is associated with an increased risk of death&#44; hospitalization&#44; anemia and a reduced quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2&#8211;4</span></a> Dialysis Outcomes and Practice Pattern Study &#40;DOPPS&#41; showed a prevalence of HCV infection in hemodialysis &#40;HD&#41; patients of 7&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> However&#44; some studies suggest that the prevalence may be underestimated due to the presence of occult HCV infection&#44; defined as the presence of HCV-RNA in hepatocytes and absence of anti-HCV antibodies in routine serological tests&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a> The risk of infection varies according to the type of renal replacement therapy &#40;being higher in patients treated with maintenance HD&#41;&#44; the time on HD&#44; and the prevalence of HCV infection in the specific dialysis unit&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">3&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Chronic HCV infection in HD patients is associated with an increase in mortality rate not only due to liver causes&#44; but also related with cardiovascular disease&#44; anemia&#44; hepatitis B virus &#40;HBV&#41; or human immunodeficiency virus &#40;HIV&#41; coinfection&#44; and essential mixed cryoglobulinemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">3&#44;5&#8211;7</span></a> In addition&#44; HCV infection contributes to an increase morbidity and mortality after kidney transplantation&#46; Indeed&#44; hepatitis C positive kidney transplantation recipients are at increased risk of developing de novo and recurrent membranous nephropathy&#44; membranoproliferative glomerulonephritis and transplant glomerulopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Anemia is a common complication of patients with chronic kidney disease&#46; Symptoms generally occur when hemoglobin levels are below 10<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; but can be more severe when kidney function worsens&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> More importantly&#44; anemia has been associated with an increased mortality and a reduced quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> There is a scarcity of information on the role of HCV and CKD-related anemia&#44; but there are some data showing that HCV positive patients have low hemoglobin levels and higher EPO dose requirements compared to uninfected patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> However&#44; the impact of HCV infection elimination on the control of anemia is unknown&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">New direct-acting antivirals &#40;DAAs&#41; have demonstrated their efficacy and safety on the treatment of HCV in patients with advanced CKD on HD&#44; with sustained virological response &#40;SVR&#41; rates ranging between 90&#37; and 100&#37; and excellent safety data&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">12&#8211;15</span></a> Therefore&#44; we hypothesized that HCV infection can be safely eliminated from HD units in order to avoid the risk of new HCV infections among HD patients and staff and that HCV elimination could impact on renal function and CKD-related complications&#46; The aims of the study were to determine the success in eliminating HCV infection from our dialysis unit after DAAs therapy in all patients on HD&#44; and to evaluate the impact of therapy on clinical and analytical outcomes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and antiviral therapy</span><p id="par0025" class="elsevierStylePara elsevierViewall">This is a prospective&#44; observational&#44; single center study&#44; in which all HCV-RNA positive patients in our HD unit &#40;at Hospital Cl&#237;nic Barcelona and its associated dialysis centers&#41; received antiviral therapy with an interferon &#40;IFN&#41;-free regimen within a 3 year period &#40;April 2014 to March 2017&#41;&#46; The antiviral regimen was decided by the treating physician based on published guidelines and information available at the time of treatment indication &#40;Asunaprevir &#91;ASV&#93;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Daclatasvir &#91;DCV&#93;&#44; Ombitasvir&#47;Paritaprevir&#47;ritonavir with or without Dasabuvir &#91;3D or 2D&#93;&#44; Grazoprevir &#91;GZR&#93;&#47;Elbasvir &#91;EBV&#93;&#44; or Sofosbuvir &#91;SOF&#93;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>DCV&#41;&#46; Direct-acting antivirals were administered according to the recommendations of the specific insert packages&#46; The usage and dose of RBV were also decided by the treating physician according to the treatment regimen recommendations and the status of the patient&#46; The duration of therapy was 12 or 24 weeks according to recommendations of the European Association for the Study of the Liver &#40;EASL&#41; guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a> Since the aim of the study was the elimination of HCV infection from HD unit&#44; the presence of significant comorbidities was not considered as a contraindication to receive antiviral therapy&#46; Potential drug&#8211;drug interactions were actively investigated and if detected&#44; concomitant medications were modified appropriately&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Monitoring</span><p id="par0030" class="elsevierStylePara elsevierViewall">For each patient&#44; data on age&#44; gender&#44; previous comorbidities&#44; time on dialysis&#44; duration of each dialysis session&#44; etiology of CKD&#44; HBV or HIV coinfection&#44; and previous HCV treatments were collected at baseline&#46; Liver tests &#40;aspartate aminotransferase &#91;AST&#93;&#44; alanine aminotransferase &#91;ALT&#93;&#44; gamma glutamyl-transpeptidase &#91;GGT&#93;&#44; alkaline phosphatase &#91;ALP&#93; and bilirubin&#41;&#44; inflammatory markers &#40;C-reactive protein&#44; CRP&#41; and parameters for the control of anemia &#40;hematocrit&#44; hemoglobin&#44; ferritin&#44; transferrin saturation index &#91;TSI&#93;&#44; dose of darbepoetin and intravenous iron&#41; were monitored monthly from 3 months before starting antiviral therapy to the end of the follow-up &#40;12 months after treatment discontinuation&#41;&#46; Liver stiffness measurements &#40;LSM&#41; were performed at baseline and 3 months after treatment discontinuation&#46; Both determinations were conducted after HD session to avoid the impact of fluid overload on LSM&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">HCV-RNA was measured by quantitative polymerase chain reaction with a lower limit of quantification of 15<span class="elsevierStyleMonospace">Y</span>IU&#47;L &#40;Versant kPCR Molecular Systems&#44; Siemens Medical Solutions Diagnostics&#44; New York&#44; USA&#41; at baseline and week 4 of antiviral therapy&#44; end of therapy and 12 weeks after treatment discontinuation&#46; Afterwards&#44; HCV-RNA was monitored every 3 months according to local protocol at the HD unit&#46; Sustained virological response &#40;SVR&#41; was considered when HCV-RNA was negative 12 weeks after the end of treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Side effects were assessed during treatment and within 12 months of treatment discontinuation&#46; All adverse events referred by the patient were collected&#46; Special attention was given to the development or worsening of anemia &#40;defined as hemoglobin levels<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&#46; The management of anemia was carried out by correcting the dose of darbepoietin and intravenous iron according to hemoglobin&#44; hematocrit&#44; ferritin&#44; and transferrin saturation index &#40;TSI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Continuous variables are expressed as mean &#40;standard deviation&#41;&#46; Categorical variables are expressed as number and percentage&#46; Comparisons between categorical variables were performed by Chi-square test or Fischer test as appropriate&#46; Comparisons between continuous variables were performed by <span class="elsevierStyleItalic">T</span>-test or non-parametric tests&#46; A one-way repeated measures ANOVA was used to determine whether there was a statistical difference between paired analyses&#46; A <span class="elsevierStyleItalic">p</span> value &#60;0&#46;05 was considered significant&#46; Statistical analysis was performed using the statistical SPSS version 23&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Effectiveness and tolerability of antiviral therapy</span><p id="par0050" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; 26 &#40;10&#37;&#41; out of the 262 attending our HD unit during the study period were anti-HCV and HCV-RNA positive&#46; During the study period&#44; 4 patients discontinued HD treatment &#40;2 due to kidney transplantation&#44; 1 patient was transfer to another center&#44; and 1 patient died due to hepatocellular carcinoma&#41;&#44; and 2 patients did not require antiviral treatment due to spontaneous HCV-RNA negativization&#46; Thus&#44; 20 patients were candidates to receive DAAs treatment&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The characteristics of the 20 treated patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Briefly&#44; 65&#37; were male&#44; with a mean age of 53&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;3 years&#44; infected with genotype 1b &#40;60&#37;&#41;&#44; and stable on HD over a period of 82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>79 months&#46; Twenty percent of patients were non-responders to a previous course of an IFN-based therapy&#46; The dialysis modality was on-line hemodiafiltration with post-dilutional infusion in all patients&#46; Twenty-five percent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; of patients had diabetes mellitus&#44; 40&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; had cirrhosis and 25&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; had other viral coinfections &#40;3 HIV infection&#44; 2 HBV infection&#41;&#46; The etiologies of CKD were&#58; glomerulonephritis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; 40&#37;&#41;&#44; diabetic nephropathy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; 15&#37;&#41;&#44; amyloidosis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 10&#37;&#41;&#44; chronic interstitial nephropathy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 10&#37;&#41;&#44; nephroangiosclerosis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 5&#37;&#41;&#44; obstructive uropathy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 5&#37;&#41;&#46; In the remaining 3 patients &#40;15&#37;&#41; the etiology of CKD was unknown&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The most commonly used DAAs regimen was Ombitasvir&#44; Paritaprevir&#47;ritonavir and Dasabuvir &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; 45&#37;&#41;&#46; Ribavirin &#40;RBV&#41; was added only in one patient infected with genotype 1a&#46; Interestingly&#44; 3 patients infected with genotypes 2 or 3 received a Sofosbuvir-based combination &#40;off-label&#41;&#46; The specific treatment&#44; dose and duration are shown in Supplementary Table 1&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">At week 4 of therapy&#44; viral load for HCV was undetectable in all patients and all of them achieved SVR&#46; No reinfections were observed in any of the subjects during the follow-up period&#46; After achieving SVR&#44; 3 patients who asked for it were relocated in dialysis shifts for HCV negative patients&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Medication was well tolerated with mild side effects in 40&#37; of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; None of these side effects led to treatment discontinuation&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Impact of therapy on clinical and analytical outcomes</span><p id="par0075" class="elsevierStylePara elsevierViewall">As expected&#44; SVR was associated with an improvement in liver tests &#40;Supplementary Table 2&#41; and liver stiffness measurement determined at the time of SVR &#40;from 9&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;1<span class="elsevierStyleHsp" style=""></span>kPa to 7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;0<span class="elsevierStyleHsp" style=""></span>kPa&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46; C-reactive protein did not change significantly changed during and after DAA therapy &#40;Supplementary Table 2&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We observed an improved control of anemia after DAAs treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; with a significant increase hemoglobin and hematocrit levels after the end of treatment &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;017 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;048&#59; respectively&#41;&#46; This was associated with a tendency toward a decrease in the dose of intravenous iron &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;064&#41;&#46; There were no significant changes in the dose of darbepoetin and ERI index&#46; In addition&#44; ferritin levels and transferrin saturation index did not significantly changed after treatment discontinuation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Here&#44; we showed for the first time that with the new DAAs treatments it is possible to eliminate HCV infection from HD units&#46; Despite the prevalence of HCV in patients on HD having declined significantly in recent years&#44; it is still higher than that of the general population carrying a significant increase in morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19&#44;20</span></a> The international observational study on the long-term guidelines and results of patients on HD &#40;DOPPS&#41; reviewed 76&#44;689 adult patients between 1996 and 2015&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> The prevalence of HCV infection observed among countries participating in all phases of DOPPS was 14&#46;3&#37; in phase 1 &#40;1996&#8211;2001&#41;&#44; 10&#46;7&#37; in phase 2 &#40;2002&#8211;2004&#41;&#44; 8&#46;8&#37; in the phase 3 &#40;2005&#8211;2008&#41;&#44; 6&#46;8&#37; in phase 4 &#40;2009&#8211;2011&#41; and 8&#46;7&#37; in phase 5 &#40;2012&#8211;2015&#41;&#46; The prevalence of HCV infection in our HD unit&#44; with a mean time in dialysis of 82&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>78&#46;7 months was 10&#37;&#44; which is slightly higher than that observed in DOPPS phase 5&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Prior to 2011&#44; standard HCV treatment was based on pegylated interferon &#40;PegINF&#41; or the combination of PegIFN and RBV&#44; which resulted in SVR rates of 40&#8211;50&#37;&#44; although their significant adverse effects and low rate of SVR&#44; limited their widespread use&#46; Despite the relatively good results in terms of efficacy in patients on HD treated with PegIFN and RBV&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a> the use of this therapy was hampered by the significantly high number of adverse events observed in this subpopulation&#46; A study by our group<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a> showed that up to 60&#37; of patients on HD treated with an IFN-based therapy early discontinued treatment due to adverse events &#40;including hematological disorders and infections&#41;&#46; This explains the low applicability of IFN-based therapies in patients on HD as shown in the DOPPS study&#44; in which only 1&#46;5&#37; of the patients included received antiviral therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The development of IFN-free therapies with different combinations of DAAs has revolutionized the treatment of patients in HD&#46; There are 3 clinical trials specifically designed to evaluate the safety and efficacy of antiviral therapy in patients with chronic kidney disease stages 4 and 5&#46; The RUBY-1<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> trial evaluated the 3D combination with or without RBV in 20 genotype 1-infected patients with CKD stages 4 and 5&#46; Overall&#44; 90&#37; &#40;18 out of the 20 patients&#41; achieved SVR12&#46; Anemia was the most common adverse event&#46; In the second part of the study&#44; 18 genotype 1a and 4 infected patients &#40;normally requiring RBV&#41; received the 3D or 2D combination without RBV and all of them achieved SVR&#46; In the C-SURFER<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> study&#44; 224 genotype 1 infected patients were randomly assigned to receive the combination of Grazoprevir and Elbasvir once daily for 12 weeks or placebo &#40;deferred treatment&#41;&#46; In the full set analysis&#44; 94&#37; and 95&#37; of patients in the immediate and the deferred treatment groups&#44; respectively&#44; achieved SVR12&#46; More recently&#44; the combination of Glecaprevir and Pibrentasvir administered for 12 weeks to 104 patients infected with different HCV genotypes and CKD stages 4 and 5 achieved an SVR of 100&#37; with excellent safety results&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Similar to the results of clinical trials or real life cohorts&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">12&#44;23&#44;24</span></a> we obtained excellent results with the different DAAs combinations administered to our cohort&#46; Most of our patients received the 3D combination for 12 weeks and all of them achieved SVR&#46; Only one patient &#40;genotype 1a&#41; required RBV and prolonged treatment duration &#40;24 weeks&#41; because of the presence cirrhosis&#46; Despite Sofosbuvir is currently not approved for the treatment of patients with a glomerular filtration rate<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; 3 of our patients &#40;infected with genotype 2 and 3&#41; with no other treatment options received Sofosbuvir in combination with Daclatasvir for 12 or 24 weeks with excellent results in terms of efficacy and safety&#46; This is similar to what has been observed in small series of cases published recently evaluating different combinations of Sofosbuvir-based regimes in which SVR rate ranged between 67&#37; and 100&#37; depending on the dose of Sofosbuvir &#40;standard dose of 400<span class="elsevierStyleHsp" style=""></span>mg per day vs&#46; 400<span class="elsevierStyleHsp" style=""></span>mg every other day or 200<span class="elsevierStyleHsp" style=""></span>mg per day&#41; and the additional drug &#40;RBV vs&#46; other DAA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20&#44;25&#8211;27</span></a> More importantly&#44; despite the concerns of using Sofosbuvir in patients on HD due to the potential side effects secondary to GS331007 &#40;principal metabolite of Sofosbuvir&#41; accumulation&#44; we and others did not observe serious adverse events in patients on HD receiving this drug&#46; However&#44; more data are needed to confirm these results and to recommend the widespread use of Sofosbuvir in patients on HD&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Interestingly&#44; we observed an improvement in the control of anemia with a significant increase in hemoglobin and hematocrit levels&#44; and a tendency toward a decrease in the dose of intravenous iron during the 12 months after treatment discontinuation&#46; The explanation for this phenomenon is unknown&#46; However&#44; one can speculate that elimination of HCV infection could improve iron metabolism and response to erythropoiesis due to a decrease in systemic inflammation&#46; The role of HCV infection on iron metabolism in patients on HD is controversial&#46; A study by Abdalla et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> showed that HCV positive patients on HD had higher EPO requirement &#40;49&#46;6 vs&#46; 14&#46;4 units&#47;kg&#47;dialysis&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; and low hemoglobin levels &#40;10&#46;5 vs&#46; 11&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41; as compared to HCV negative patients&#46; However&#44; more recent studies have shown opposite results&#46; For example&#44; Khurana et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> found that HCV positive patients required low EPO dose as compared to HCV negative counterparts &#40;253 vs&#46; 460 units&#47;kg&#47;month&#41; with no significant differences in other parameters&#46; In addition&#44; the number of patients not requiring EPO was significantly higher among HCV positive patients&#46; Since&#44; CKD-related anemia is associated with significant morbidity and mortality&#59; the improvement in the control of anemia could improve cardiovascular risk&#44; long-term survival&#44; and quality of life&#46; Obviously&#44; the limited number of patients included in the study and the short follow-up duration &#40;up to 1 year after treatment discontinuation&#41; preclude us to draw a formal conclusion&#46; However&#44; new studies&#44; with longer follow-up of treated patients&#44; would be interesting to confirm this hypothesis&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In order to prevent HCV transmission in HD units&#44; KDIGO &#40;Kidney Disease Improving Global Outcomes&#41; guidelines recommend to strictly adhering to infection-control procedures&#46; However&#44; isolation of HCV infected patients or using specifically dedicated machines for these patients is not recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> In our unit&#44; we follow these recommendations but all HCV positive patients are located in dialysis shifts with a specific nurse devoted to their care following the international recommendations to avoid blood-borne pathogens&#46; There is no information on the literature regarding the management of HD patients achieving SVR after antiviral therapy&#46; In our unit viral elimination&#44; at the time of SVR achievement &#40;3 months after the end of therapy&#41; patients are relocated to HCV negative dialysis shift&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study has several limitations&#44; including the low number of patients enrolled&#44; the absence of patients infected with less frequent genotypes&#44; and the lack of a standardized treatment for all patients due to the rapid evolution of antiviral treatments within the past few years&#46; However&#44; this is a proof of concept that HCV infection can be eliminated from HD units by treating all patients &#40;including patients with severe comorbidities&#41; by a multidisciplinary team of experts in the management of this subpopulation&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; with the incorporation of new DAAs it is possible to eradicate HCV from dialysis units&#46; The variety of therapeutic possibilities&#44; along with the high efficacy and good tolerance of these drugs allows treating and curing the whole dialysis population&#46; HCV elimination in HD units is a major breakthrough that should allow a zero incidence of hepatitis C infections&#46; Despite further research and validation is required&#44; it appears that HCV elimination is associated&#44; at individual level&#44; to an improvement in the control of anemia&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">MCL has received advisory fees from Janssen&#44; Abbvie&#44; Gilead&#44; MSD and BMS&#46; The other authors have declared no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Resumen"
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            1 => array:2 [
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study design and antiviral therapy"
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              "identificador" => "sec0020"
              "titulo" => "Monitoring"
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              "identificador" => "sec0025"
              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
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            0 => array:2 [
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              "titulo" => "Effectiveness and tolerability of antiviral therapy"
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            1 => array:2 [
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              "titulo" => "Impact of therapy on clinical and analytical outcomes"
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          "titulo" => "Discussion"
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          "identificador" => "sec0050"
          "titulo" => "Conflict of interest"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-06-07"
    "fechaAceptado" => "2018-07-29"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec1089786"
          "palabras" => array:4 [
            0 => "Elimination"
            1 => "Hemodialysis"
            2 => "Hepatitis C virus"
            3 => "Sustained virologic response"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1089785"
          "palabras" => array:4 [
            0 => "Eliminaci&#243;n"
            1 => "Hemodi&#225;lisis"
            2 => "Virus de la hepatitis C"
            3 => "Respuesta viral sostenida"
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In the interferon era&#44; the treatment of hepatitis C virus &#40;HCV&#41; infection in patients on haemodialysis &#40;HD&#41; was limited due to the significant number of treatment-related adverse events &#40;AEs&#41;&#46; Direct-acting antivirals &#40;DAAs&#41; have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis&#46; The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs&#44; and to assess the impact of HCV elimination on clinical and analytical outcomes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This is a prospective&#44; interventional&#44; single-center study at Hospital Cl&#237;nic de Barcelona&#46; All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period &#40;2014&#8211;2017&#41; were analyzed &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#46; Data on virologic response&#44; adverse events&#44; and biochemical and hematological parameters during and after DAA therapy were analyzed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All patients achieved sustained virologic response &#40;SVR&#41; and only 40&#37; of patients presented with mild AEs&#46; None of the patients presented with HCV reinfection after a 1-year follow-up period&#44; and thus HCV was eliminated from our HD unit&#46; SVR was associated with a significant increase in hemoglobin and hematocrit&#44; and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HCV infection can be safely eliminated from HD units with the use of DAAs&#44; preventing new infections in patients and healthcare staff&#46; In the short term&#44; the achievement of SVR is associated with an improvement in the control of anemia&#46;</p></span>"
        "secciones" => array:4 [
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            "titulo" => "Patients and methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">En la &#233;poca del interfer&#243;n&#44; el tratamiento del virus de la hepatitis C &#40;VHC&#41; en pacientes en hemodi&#225;lisis &#40;HD&#41; se ve&#237;a limitado por la presencia de efectos adversos relacionados con el tratamiento&#46; Los agentes antivirales directos &#40;AAD&#41; han demostrado ser seguros y eficaces en el tratamiento del VHC en pacientes con insuficiencia renal cr&#243;nica en hemodi&#225;lisis&#46; El objetivo del estudio fue evaluar el &#233;xito en eliminar la infecci&#243;n por VHC de nuestra unidad de di&#225;lisis con el uso de AAD&#44; y determinar el impacto cl&#237;nico y anal&#237;tico de la curaci&#243;n de la infecci&#243;n&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Para ello se realiz&#243; un estudio prospectivo de intervenci&#243;n en el Hospital Clinic de Barcelona y su centro de di&#225;lisis&#46; Se incluyeron todos los pacientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; con ARN-VHC positivo que recibieron tratamiento antiviral con AAD durante un periodo de 3 a&#241;os &#40;2014-2017&#41;&#46; Se analizaron los datos de respuesta virol&#243;gica&#44; efectos adversos y par&#225;metros hematol&#243;gicos y bioqu&#237;micos durante y despu&#233;s del tratamiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Todos los pacientes alcanzaron una respuesta viral sostenida &#40;RVS&#41; y solo una 40&#37; presentaron efectos adversos leves&#46; Ning&#250;n paciente present&#243; reinfecci&#243;n por el VHC y por ello tras un a&#241;o de seguimiento se consider&#243; la eliminaci&#243;n del VHC de nuestra unidad de di&#225;lisis&#46; La RVS se asoci&#243; con aumento significativo de la hemoglobina y el hematocrito&#44; y una tendencia a la necesidad de una dosis m&#225;s baja de suplemento de hierro sin cambios en la dosis de darbepoetina&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Con la utilizaci&#243;n de AAD&#44; la infecci&#243;n por el VHC puede ser eliminada de forma segura de las unidades de di&#225;lisis&#44; previniendo la transmisi&#243;n de la infecci&#243;n a pacientes y personal sanitario&#46; A corto plazo&#44; la RVS se asoci&#243; con una mejor&#237;a en el control de la anemia&#46;</p></span>"
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            "apendice" => "<p id="par0135" class="elsevierStylePara elsevierViewall">The following is the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0060"
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of the patients with HCV infection detected in the HD unit&#46;</p>"
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        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Evolution of hematological parameters after treatment discontinuation&#46; Data were analyzed using one-way repeated measures ANOVA&#46; EOT&#58; End of therapy&#44; SVR12&#58; 12 weeks after treatment discontinuation&#44; SVR24&#58; 24 weeks after treatment discontinuation&#44; SVR48&#58; 48 weeks after treatment discontinuation&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age&#44; years &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Gender male&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;65&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diabetes mellitus&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Cirrhosis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Coinfection&#44; n&#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>HBV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Genotype&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;60&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>2c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Previous antiviral treatment&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Current antiviral treatment&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Asunaprevir&#47;Daclatasvir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grazoprevir&#47;Elbasvir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Paritaprevir&#47;Ombitasvir&#47;Dasabuvir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Paritaprevir&#47;Ombitasvir&#47;Dasabuvir&#47;Ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Simeprevir&#47;Daclatasvir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sofosbuvir&#47;Daclatasvir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Adverse effects&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the patients included in the study&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as median &#40;range&#41;&#46; EOT&#58; end of therapy&#44; SVR12&#58; 12 weeks after treatment discontinuation&#44; SVR24&#58; 24 weeks after treatment discontinuation&#44; SVR48&#58; 48 weeks after treatment discontinuation&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hemoglobin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hematocrit &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EV iron dose &#40;mg&#47;week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Darbepoetin dose &#40;mcg&#47;week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ERI IU&#47;week&#47;kg&#47;g Hb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ferritin &#40;&#956;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TSI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">112&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">489<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EOT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">110&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">305<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">310<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">339<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SVR48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">390<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>232&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-Value<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;048&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;064&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;707&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1987551.png"
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            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">p</span>-Value was determined by one-way repeated measure ANOVA&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Hematological parameters during and after treatment discontinuation&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
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        "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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient number&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse event&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Arthralgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heartburn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diarrhea and pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patient 20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1987552.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Adverse events reported during antiviral therapy&#46;</p>"
        ]
      ]
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        "identificador" => "upi0005"
        "tipo" => "MULTIMEDIAECOMPONENTE"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Ecomponente" => array:2 [
          "fichero" => "mmc1.docx"
          "ficheroTamanyo" => 17612
        ]
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:29 [
            0 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global epidemiology and genotype distribution of the hepatitis C virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Gower"
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Article information

ISSN: 24443824
Original language: English

DOI:10.1016/j.gastre.2019.02.029

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	10	3	13
2024 October	14	1	15
2024 September	23	2	25
2024 August	22	9	31
2024 July	19	4	23
2024 June	18	0	18
2024 May	9	3	12
2024 April	26	5	31
2024 March	24	5	29
2024 February	43	4	47
2024 January	45	1	46
2023 December	30	2	32
2023 November	17	4	21
2023 October	21	6	27
2023 September	10	3	13
2023 August	21	3	24
2023 July	20	2	22
2023 June	26	2	28
2023 May	45	5	50
2023 April	46	2	48
2023 March	34	3	37
2023 February	16	2	18
2023 January	30	3	33
2022 December	29	4	33
2022 November	33	6	39
2022 October	27	11	38
2022 September	27	7	34
2022 August	24	10	34
2022 July	20	6	26
2022 June	26	11	37
2022 May	25	5	30
2022 April	23	12	35
2022 March	39	8	47
2022 February	35	9	44
2022 January	38	6	44
2021 December	20	11	31
2021 November	24	17	41
2021 October	33	11	44
2021 September	14	16	30
2021 August	34	6	40
2021 July	19	5	24
2021 June	23	9	32
2021 May	25	8	33
2021 April	35	1	36
2021 March	19	1	20

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