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1.
Proc Natl Acad Sci U S A ; 108(9): 3719-24, 2011 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-21321200

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Predisposición Genética a la Enfermedad , Hepacivirus/fisiología , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Interleucinas/genética , Polimorfismo de Nucleótido Simple/genética , Antivirales/administración & dosificación , Quimioterapia Combinada , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Interferones , Cinética , Modelos Biológicos , Análisis Multivariante , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Factores de Tiempo , Carga Viral
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