title: Profound week 4 interferon responsiveness is mandatory for hepatitis C genotype 1 patients with unfavorable IL-28B genotype.
abstract: BACKGROUND
  Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection.
  
  
  OBJECTIVE
  We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment).
  
  
  METHODS
  Rs8099917 genotypes were determined in 528 HCV-1 patients with peginterferon/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log(10) IU/mL, 1-2 logs(10) IU/mL, 2-3 logs(10) IU/mL, 3-4 logs(10) IU/mL and ≥4 logs(10) IU/mL reduction and/or undetectable HCV RNA, respectively.
  
  
  RESULTS
  The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P < 0.0001), lower body mass index (P = 0.0056), lower aspartate aminotransferase levels (P = 0.0009), higher hemogloblin concentration (P = 0.0033), higher platelet counts (P < 0.0001), male gender (P < 0.0001) and rs809997 TT-genotype (P < 0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1-3 logs(10) IU/mL) at week 4 (58.9% vs. 18.2%, P < 0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log(10) IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs(10) reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR.
  
  
  CONCLUSIONS
  More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000032:analysis; D015992:Body Mass Index; D004359:Drug Therapy, Combination; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006579:Heterozygote; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D001219:Aspartate Aminotransferases; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a