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

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 ro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-03, Vol.108 (9), p.3719-3724
Main Authors: Hsu, Ching-Sheng, Hsu, Shih-Jer, Chen, Hung-Chia, Tseng, Tai-Chung, Liu, Chen-Hua, Niu, Wei-Fang, Jeng, Jenher, Liu, Chun-Jen, Lai, Ming-Yang, Chen, Pei-Jer, Kao, Jia-Horng, Chen, Ding-Shinn
Format: Article
Language:English
Subjects:
Antiviral Agents - administration & dosage
Antiviral Agents - therapeutic use
Biological Sciences
Chronic hepatitis
Drug Therapy, Combination
Genes
Genetic Predisposition to Disease
Genotype & phenotype
Genotypes
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - virology
Humans
Infections
Interferon alpha-2
Interferon-alpha - administration & dosage
Interferon-alpha - therapeutic use
Interferons
Interleukins - genetics
Kinetics
Mathematical models
Medical treatment
Models, Biological
Multivariate Analysis
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - therapeutic use
Polymorphism
Polymorphism, Single Nucleotide - genetics
Recombinant Proteins
Ribavirin - administration & dosage
Ribavirin - therapeutic use
RNA
Time Factors
Viral Load
Virions
Virology
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Summary: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 = 10⁶-10¹²) 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1100349108