title: Value of interleukin-28B genetic polymorphism on retreatment outcomes of chronic hepatitis C genotype 1 relapsers by peginterferon alfa plus ribavirin.
abstract: OBJECTIVE
  Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation.
  
  
  METHODS
  A total of 75 CHC genotype 1 Taiwanese patients who relapsed after 24-week PEG-IFN/RBV combination therapy and received retreatment with a 48-week PEG-IFN/RBV therapy were consecutively enrolled since November 2009. The associations among IL28B rs8099917 genotype, virologic kinetics, and treatment outcomes were evaluated.
  
  
  RESULTS
  Rapid virologic response (RVR) at week 4, end-of-treatment virologic response (EOT-VR) and SVR was 37%, 73%, and 52%, respectively. Relapse rate was 29%. None of patients had rs8099917 GG genotype. Patients with TT genotype (n = 54, 72%) had higher rates of RVR (50% vs 5%, P = 0.0002), end-of-treatment virologic response (85% vs 43%, P = 0.0001), and SVR (67% vs 14%, P = 0.0001) than those with GT genotype (n = 21, 28%). Combination of IL28B TT genotype and achieving RVR had 85% positive and 90% negative predictive values of SVR.
  
  
  CONCLUSIONS
  About half of the Taiwanese CHC relapsers to a previous 24-week combination therapy achieve SVR after retreatment for 48 weeks. IL28B genotype influences on-treatment viral kinetics and SVR rate in these retreated patients. Baseline IL28B genotype and RVR can serve as early predictors for treatment success.
authors.affiliation: Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chen
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Ting-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; 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; C100416:peginterferon alfa-2a
keywords: IL28B; chronic hepatitis C; genotype; pegylated interferon; retreatment