title: Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.
  
  
  METHODS
  The sustained virological response (SVR) rate, IL28B genotype, IFNL4 genotype, initial viral load (IVL) and other pretreatment variables in 39 end-stage renal disease patients (ESRD) on maintenance haemodialysis (HD) infected with hepatitis C virus (HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment naïve and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a (PegIFN-α) weekly and a reduced dose of ribavirin (RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/dL. Control group patients were given standard doses of PegIFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ(2) test compared the frequencies. Logistic regression was used to determine significant predictors of SVR. Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.
  
  
  RESULTS
  The distribution of IL28B rs12979860 CC, CT and TT genotypes in the ESRD group was 28.2%, 64.1% and 7.7%, respectively, and 19.3%, 62.4% and 18.3% in the controls. The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B. The proportion of patients with a low IVL (< 600000 IU/mL) was significantly higher in the ESRD group than in the controls (28/39, 71.8% vs 51/109, 46.8%, P = 0.009), as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group (10/11, 90.9% vs 18/28, 64.3%, P = 0.0035). This difference was not found in the controls (7/22, 31.8% vs 44/87, 50.6%, P = 0.9). The overall SVR rate was 64.1% (25/39) in the ESRD group and 50.5% (55/109) in the control group (P = 0.19). 11/11 (100%) and 19/22 (86.4%) IL28B CC patients achieved SVR in the ESRD and control groups, respectively. A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups. The ESRD patients who achieved SVR showed the lowest IVL [median 21000, interquartile range (IQR): 6000-23000 IU/mL], compared with ESRD individuals without SVR (1680000, IQR: 481000-6880000, P = 0.001), controls with SVR (387000, IQR: 111000-1253000) and controls without SVR (905000, IQR: 451000-3020000). In ESRD, an IVL < 600000 IU/mL was strongly associated with SVR: 24/28 (85.7%) patients who achieved SVR had viraemia below this threshold.
  
  
  CONCLUSIONS
  Haemodialysis decreases the viral load, especially in IL28B CC genotype carriers. A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sperl
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Frankova
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Senkerikova
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Neroldova
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Hejda
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Volfova
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Dusan
authors.initials: D
authors.lastname: Merta
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Julius
authors.initials: J
authors.lastname: Spicak
authors.affiliation: Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Jirsa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human; C100416:peginterferon alfa-2a
keywords: End-stage renal disease; Hepatitis C virus genotype 1; IFNL4; Interferon alpha; Ribavirin