Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with pegylated interferon plus ribavirin therapy.

Abstract

BACKGROUND AND AIMS: Asian chronic hepatitis C (CHC) patients are known to have better virologic responses to pegylated interferon-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics also plays a role remains unclear. METHODS: A total of 145 consecutive Taiwanese CHC patients with pegylated interferon (Peg-IFN) plus ribavirin were enrolled. Blood samples were taken frequently in the first 3 days. A dose of Peg-IFN was administered at week 1, and then weekly with daily ribavirin for 24 or 48 weeks. A new mathematical model was fitted to the observed HCV kinetics. Results: A model of the virus acceleration which could interpret the transient hepatitis C viral titer elevation after Peg-IFN treatment was constructed. Our patients had a comparable viral clearance rate (c=3.45+3.73) (day-1, mean+SD) but lower daily viral production rate (p=106~1012) than previously reported Western patients. After the first dosing of Peg-IFN, viral titer declined in most patients. Of 110 patients with sustained virologic response (SVR), 47 (43%) had transient viral titer elevation within 12 hours (proportion of 12hours/3days, 44% in Non-SVR vs. 70% in SVR, p=0.029). Among 91 patients with available rs8099917 data, patients with TT genotype had an early surge of viral titer after therapy, higher SVR and viral clearance rate than those with GT genotype. CONCLUSIONS: Taiwanese CHC patients with interferon-based therapy have a lower daily viral production rate than the known estimates from Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance and better virologic response rate in these patients. (Table presented).