Factors predictive of response to interferon‐α therapy in hepatitis C virus type 1b infection

Abstract

Interferon-alpha (IFN-alpha) has been used to treat hepatitis C Virus (HCV)-induced infection but has been effective in only about half of all patients. It is suggested that the different responses to IFN-alpha treatment in HCV infection may be influenced by HCV genotypes, HCV RNA titer at the beginning of IFN-alpha therapy, and the sequences of the interferon sensitivity determining region (ISDR). However, there have also been reports showing that these have no relation to an IFN-alpha effect. In a previous study, it was found that the nucleotide sequence variation in the hypervariable region (HVR) 1 of the HCV could predict the effect of IFN-alpha. In the present investigation, an attempt was made to determine the predictive factors of IFN-alpha therapy. Twenty-six patients with HCV infection were treated with IFN-alpha. Among these, 13 patients recovered after 3 to 6 months of IFN-alpha treatment, although the other 13 patients showed no response after 6 months of treatment with IFN-alpha. In order to determine the predictive factors of IFN-alpha therapy, the ALT levels, HCV genotypes, HCV serum titer, and the quasispecies of HVR 1 were compared between responders and non-responders. It is suggested that the variation in the HVR 1 and HCV serum titer can be used to predict the effect of IFN-alpha.

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

“…mutations not resulting in aminoacidic substitution [12]; a similar correlation was found in non-responder patients undergoing a second course of IFN treatment [13]. In addition, virus quasispecies complexity at baseline in patients with no response (NR) was higher than that observed in patients with undetectable viremia at 6 months [14]. In contrast, in a recent paper, baseline diversity and complexity were comparable in patients with sustained response (SR), NR and relapse (Rel), whereas the evolution of viral quasispecies early after starting therapy was different in the three groups [7].…”

“…Among these, Yeh et al [14] showed that the extent of viral heterogeneity at baseline may be predictive of early (6 months) outcome, while Farci et al [7] and Sookoian et al [16], indicated that heterogeneity of HVR-1 region is not predictive of sustained response, showing association of baseline heterogeneity with early, but not sustained response. However, the first study was based on IFN monotherapy, and there was the possibility that suboptimal therapeutic pressure could determine the loss of influence of virus heterogeneity when considering longterm response.…”

Wide Range of Quasispecies Diversity during Primary Hepatitis C Virus Infection

“…A lower level of viral genetic diversity in subjects who cleared their viremia versus those who established a chronic infection has been reported (58). While therapeutic intervention strongly affects the variant composition of HCV quasispecies, contradictory results have appeared regarding the influences of viral genetic diversity per se on the therapeutic response rate (1,17,20,24,26,53,56,61,64,70). The higher therapeutic response rate of recently infected versus long-term-infected patients (28, 46) could conceivably be related to the generally less genetically diverse quasispecies expected early in infection.…”

Quasispecies Heterogeneity within the E1/E2 Region as a Pretreatment Variable during Pegylated Interferon Therapy of Chronic Hepatitis C Virus Infection

“…Infection with HCV is followed by the occurrence of persistent disease in the majority of cases, which is associated with a viremia that reflects productive replication of virus in the liver, estimated to yield as many as a trillion virus particles per day (28). Factors involved in either the spontaneous clearance of HCV or clearance associated with antiviral therapy have been partially elucidated and involve both viral and host determinants (8,9,43,46). Among viral factors, it has been demonstrated that genetic heterogeneity of the virus at the level of quasispecies populations impacts on the evolution of chronic infection, with the development of more complex populations of virus associated with an inability to clear acute infection (8).…”