title: Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy.
abstract: Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity-determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin-28B (IL-28B) locus affect the outcome of interferon (IFN)-based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response-guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV-1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non-EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts≥15×10(4) /μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: C-M
authors.initials: CM
authors.lastname: Liang
authors.forename: T-H
authors.initials: TH
authors.lastname: Hu
authors.forename: S-N
authors.initials: SN
authors.lastname: Lu
authors.forename: C-H
authors.initials: CH
authors.lastname: Hung
authors.forename: C-M
authors.initials: CM
authors.lastname: Huang
authors.forename: J-H
authors.initials: JH
authors.lastname: Wang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Yen
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: K-C
authors.initials: KC
authors.lastname: Chang
authors.forename: M-C
authors.initials: MC
authors.lastname: Tsai
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kuo
authors.forename: C-M
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D000095022:Interferon Lambda; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: core protein; hepatitis C virus; interferon sensitivity-determining region; interleukin-28B; sustained virological response