Dynamics of serum hepatitis C virus load and quasispecies complexity during antiviral therapy in patients with chronic hepatitis C

Background: Hepatitis C virus (HCV) infection is a dynamic process during w hich viral genetic variants continuously develop as a result of the virus a daptation to the host's immune system. The level of viremia and the complex ity of the hypervariable region 1 (HVR 1) quasispecies of hepatitis C virus during antiviral therapy reflect the dynamic balance between the viral and host components in response to therapy. Objective: The aim of the study wa s to evaluate the dynamics of HCV viremia and the complexity of the HVR 1 q uasispecies during the induction phase of a triple combination therapy regi men in nonresponders to earlier anti-HCV treatment. Study design: Ten patie nts with chronic hepatitis C undergoing antiviral combination therapy with interferon-alpha, ribavirin, and amantadine were studied. The serum HCV RNA level was monitored by a quantitative RT-PCR assay up to 3 months after st art of treatment. The HVR 1 quasispecies complexity was analysed by an 'in house' nested RT-PCR mediated single-strand conformation polymorphism (SSCP ) assay. Results: Baseline serum HCV RNA levels ranged from 1.94 x 10(6) to 5.53 x 10(6) copies/ml. In all patients, HCV subtype Ib was found. At the start of therapy, the SSCP assay revealed a high complexity pattern (at lea st six SSCP bands) in all patients. None of the patients responded within 4 weeks of treatment, however, the serum HCV RNA level decreased by one to t wo logs in eight patients. At week 4 after start of treatment, there was a decrease of SSCP bands in five patients. In four patients, SSCP bands remai ned unchanged and in one patient SSCP bands increased. Al month 3 after sta rt of treatment, serum HCV RNA was not detectable in one patient. Conclusio n: Because of the low number of patients involved in this study, prediction of therapeutical success based on the quasispecies complexity was not poss ible. Larger studies are urgently needed. (C) 2001 Elsevier Science B.V. Al l rights reserved.