title: Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy.
abstract: Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day(-1), mean ± SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei 23142, Taiwan.
authors.forename: Ching-Sheng
authors.initials: CS
authors.lastname: Hsu
authors.forename: Shih-Jer
authors.initials: SJ
authors.lastname: Hsu
authors.forename: Hung-Chia
authors.initials: HC
authors.lastname: Chen
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Niu
authors.forename: Jenher
authors.initials: J
authors.lastname: Jeng
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007700:Kinetics; D008954:Models, Biological; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; 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