Influence of viral load and alanine aminotransferase on viral genetic heterogeneity in patients with chronic hepatitis C virus infection

Background/Aim: Hepatitis C virus (HCV) populations in vivo consist of gene tically different heterogeneous mixtures defined as 'quasispecies', which v ary in the hypervariable region 1 (HVR1) mostly. To further address the rol e of quasispecies diversity in hepatitis C infection, this study aimed to e valuate the influence of ALT, viral load and genotypes on quasispecies hete rogeneity in patients with HCV infection. Methods: Thirty-six chronic hepat itis C patients with high levels of alanine aminotransferase (ALT) were stu died. None of them received any antiviral therapy. HCV RNA serum levels, ge notype and genetic heterogeneity were determined by branched-chain DNA assa y, restriction fragment length patterns and RT-PCR single-strand conformati onal polymorphism analysis of HVR1, respectively. Results: Twenty-eight pat ients had genotype 1b (28/36; 78%), 6 patients had genotype 1a (6/36; 17%), 1 patient was 2a (1/36; 3%) and genotype could not be determined in 1 pati ent. The patients were categorized into two groups according to the number of bands representing the dominant strains in the circulation: group A with 2 bands having 1 strain (14/36 patients; 39%) and group B with more than 2 bands indicating more than 1 strain (22/36 patients; 61%). The serum virem ia and ALT levels for these groups were 11 +/- 8.8 and 5.3 +/- 4.6 mEq/ml ( p < 0.05), and 79 +/- 20, and 127 +/- 80 IU/l (p < 0.05), respectively. Con clusion: The results of this study suggest that hepatitis C patients having 1 dominant strain in the circulation may show a relatively weaker immune r esponse resulting in lower ALT and higher viremia levels, whereas patients with high degrees of virus quasispecies diversity have higher ALT levels an d a more active immune response causing the selection of new genome variant s and depressing viral replication partly. Copyright (C) 2000 S. Karger AG, Basel.