Profound week 4 interferon responsiveness is mandatory for hepatitis C genotype 1 patients with unfavorable IL-28B genotype

Abstract

BackgroundViral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection. ObjectivesWe 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 designsRs8099917 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. ResultsThe 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. ConclusionsMore profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype.