Profound week 4 interferon responsiveness is mandatory for hepatitis C genotype 1 patients with unfavorable IL-28B genotype
Journal
Journal of Clinical Virology
Journal Volume
56
Journal Issue
4
Pages
293-298
Date Issued
2013
Author(s)
Huang C.-F.
Yu M.-L.
Yeh M.-L.
Huang J.-F.
Dai C.-Y.
Lin Z.-Y.
Chen S.-C.
Wang L.-Y.
Juo S.H.H.
Chuang W.-L.
Abstract
Background: Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection. Objectives: We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment). Study designs: Rs8099917 genotypes were determined in 528 HCV-1 patients with peginterferon/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log10 IU/mL, 1-2 logs10 IU/mL, 2-3 logs10 IU/mL, 3-4 logs10 IU/mL and ?4 logs10 IU/mL reduction and/or undetectable HCV RNA, respectively. Results: The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P<0.0001), lower body mass index (P=0.0056), lower aspartate aminotransferase levels (P=0.0009), higher hemogloblin concentration (P=0.0033), higher platelet counts (P<0.0001), male gender (P<0.0001) and rs809997 TT-genotype (P<0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1-3 logs10 IU/mL) at week 4 (58.9% vs. 18.2%, P<0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log10 IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs10 reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR. Conclusions: More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype. ? 2012 Elsevier B.V.
SDGs
Other Subjects
aspartate aminotransferase; hemoglobin; interleukin 28B; peginterferon alpha2a plus ribavirin; peginterferon alpha2b plus ribavirin; adult; article; Asian; body mass; clinical feature; female; gene; genetic polymorphism; groups by age; hepatitis C; human; interleukin 28B gene; major clinical study; male; priority journal; RNA virus; sex difference; thrombocyte count; treatment duration; treatment outcome; treatment response; Adult; Age Factors; Aged; Antiviral Agents; Aspartate Aminotransferases; Body Mass Index; Drug Therapy, Combination; Female; Genetic Testing; Genotype; Hemoglobins; Hepacivirus; Hepatitis C, Chronic; Heterozygote; Humans; Interferon-alpha; Interleukins; Male; Middle Aged; Platelet Count; Polyethylene Glycols; Recombinant Proteins; Ribavirin; RNA, Viral; Sex Factors; Time Factors; Treatment Outcome
Type
journal article