Ultra-Rapid Virological Response, Young Age, Low gamma-GT/ALT-Ratio, and Absence of Steatosis Identify a Subgroup of HCV Genotype 3 Patients Who Achieve SVR with IFN-alpha(2a) Monotherapy

Abstract

Background and Aims The standard treatment regimen for chronic HCV genotype 3 (HCV-G3) hepatitis consists of PEGylated interferon-alpha (IFN-alpha) and ribavirin at varying doses ranging from 400 to 1,200 mg and results in response rates of 80%. However, this therapy has substantial side-effects including anemia, is teratogenic, and costly. To reduce the side-effects of therapy, the role of monotherapy consisting of only IFN-alpha was investigated. Methods A retrospective analysis of individual therapy courses of HCV-G3-infected patients who were treated with IFN-alpha(2a) monotherapy or a combination therapy with attention to the treatment outcome and the presence of IL28B rs12979860 and IL28B rs8099917 single-nucleotide polymorphism genotypes was performed. Conventional prognostic features in each case were assessed as well. Results In the study, 15/30 (50%) of patients treated with IFN-alpha(2a) monotherapy and 32/36 (89%) treated with combination therapy achieved a sustained virological response (SVR). In addition, 7/11 (64%) of those treated initially with monotherapy and subsequently with combination therapy achieved an SVR. An "ultra-rapid" virological response occurring within 2 weeks of initiation of therapy (p = 0.005), young age (< 40; p < 0.001) and low initial gamma-GT/ALT-ratio (p = 0.03) were associated with a SVR to IFN-alpha(2a) monotherapy. An SVR in those treated with combination therapy was found to be associated with a rapid virological response (RVR) (p = 0.03). The absence of histologic steatosis was associated with SVR in all patient groups (p = 0.01). Therapy duration (24 vs. 48 weeks) did not affect the SVR in either group. As expected, combination therapy resulted in more hematological side-effects than did monotherapy. Conclusions An "ultra-rapid" virological response, young age, low initial gamma-GT/ALT-ratio and absence of steatosis were each associated with an SVR in those receiving IFN-alpha(2a) monotherapy. Therefore, monotherapy in these patients should still be discussed independently of the existence of the IL28B polymorphisms.