title: Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study.
abstract: BACKGROUND
  The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment.
  
  
  METHODS
  Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy.
  
  
  RESULTS
  The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p=0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p=1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p=0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy.
  
  
  CONCLUSIONS
  In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. nonahu5248@gmail.com.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Hu
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. wn49792000@yahoo.com.tw.
authors.forename: Chih-Lang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. lc2008@adm.cgmh.org.tw.
authors.forename: Liang-Che
authors.initials: LC
authors.lastname: Chang
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. cashtoto@gmail.com.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Chien
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. leiwei@adm.cgmh.org.tw.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. cjliuu@cgmh.org.tw.
authors.forename: Ching-Jung
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan. ronald@adm.cgmh.org.tw.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012720:Severity of Illness Index; D017211:Treatment Failure; D019562:Viral Load; 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