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

• Published in: Journal of clinical virology 2001, Vol.20 (1), p.85-89
• Main Authors: Grahovac, Blazenka, Bingulac-Popovic, Jasna, Vucelic, Boris, Hrstic, Irena, Ostojic, Rajko, Drazic, Vesna, Balija, Melita, Grgicevic, Damir
• Format: Article
• Language: English
• Subjects: Adult; Amantadine - pharmacology; Amantadine - therapeutic use; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; DNA, Viral - blood; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; HCV viremia; Hepacivirus - classification; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; hypervariable region 1; Interferon-alpha - pharmacology; Interferon-alpha - therapeutic use; Male; Microbiology; Middle Aged; Phylogeny; Polymorphism, Single-Stranded Conformational; Quasispecies; quasispecies complexity; Reverse Transcriptase Polymerase Chain Reaction; Ribavirin - pharmacology; Ribavirin - therapeutic use; Triple combination therapy; Viral Load
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/S1386-6532(00)00160-8

Background: Hepatitis C virus (HCV) infection is a dynamic process during which viral genetic variants continuously develop as a result of the virus adaptation to the host's immune system. The level of viremia and the complexity 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 was to evaluate the dynamics of HCV viremia and the complexity of the HVR 1 quasispecies during the induction phase of a triple combination therapy regimen in nonresponders to earlier anti-HCV treatment. Study design: Ten patients 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 start 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 1.94×10 6 to 5.53×10 6 copies/ml. In all patients, HCV subtype 1b was found. At the start of therapy, the SSCP assay revealed a high complexity pattern (at least 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 two 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 remained unchanged and in one patient SSCP bands increased. At month 3 after start of treatment, serum HCV RNA was not detectable in one patient. Conclusion: Because of the low number of patients involved in this study, prediction of therapeutical success based on the quasispecies complexity was not possible. Larger studies are urgently needed.