HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b

Abstract

BackgroundThe impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.MethodsFor 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).ResultsThe rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.ConclusionDual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.Trial registrationClinicalTrials.gov Identifier: NCT01342003

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

“…Of note, neither HCV RNA levels nor IL28B distribution differed in patients infected with the two subtypes. A similar age difference and male prevalence was noted in another Italian study (11).…”

“…Results from the considered studies are summarized in the Supplementary (11)(12)(13), and two studies with significantly better rates in patients with subtype 1b (8,9). By pooling results from previous studies with those of the present investigation (Figure 2), the weighted SVR rates were not different between the two viral strains: OR = 0.98, CI 0.72-1.32.…”

“…Up to now, genotyping for HCV-1 subtypes will not impact on the day-to-day clinical management of chronic HCV infection, whereas conflicting reports exist on their influence on the outcome following conventional therapy with Peg-IFN and RIBA (6)(7)(8)(9)(10)(11)(12)(13). Recently, several HCV inhibitors appear to have selective activity against HCV 1 subtypes both in vitro and in vivo, with subtype 1a appearing more resistance-prone and less responsive to triple therapy than subtype 1b (25)(26)(27)(28)).…”

“…Major clinical trials evaluated treatment response among HCV-1a and 1b patients grouped together and, consequently, were unable to unveil a differential outcome of treatment between the two viral strains. Of available trials (7)(8)(9)(10)(11)(12)(13)(14), only few studies were sufficiently powered to detect an eventual difference, with some reporting a lower efficacy of Peg-IFN and RIBA in HCV-subtype 1a, and other studies unraveling an opposite finding. In addition, the impact of HCV-1 subtypes on the on-treatment response milestones, such as the rapid viral response at treatment week 4 (RVR), has not been extensively investigated.…”

HCV genotype 3: a wolf in sheep’s clothing

“…This is something we already known for HCV G1a and 1b. [38] At least 10 HCV G3 subtypes have been described so far. [39] Are some of these HCV G3 subtypes able to evade the immune response?…”