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

Intervirology. 2000;43(1):61-6. doi: 10.1159/000025024.

Abstract

Background/aim: Hepatitis C virus (HCV) populations in vivo consist of genetically different heterogeneous mixtures defined as 'quasispecies', which vary in the hypervariable region 1 (HVR1) mostly. To further address the role of quasispecies diversity in hepatitis C infection, this study aimed to evaluate the influence of ALT, viral load and genotypes on quasispecies heterogeneity in patients with HCV infection.

Methods: Thirty-six chronic hepatitis C patients with high levels of alanine aminotransferase (ALT) were studied. None of them received any antiviral therapy. HCV RNA serum levels, genotype and genetic heterogeneity were determined by branched-chain DNA assay, restriction fragment length patterns and RT-PCR single-strand conformational polymorphism analysis of HVR1, respectively.

Results: Twenty-eight patients 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 patient. 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 viremia 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.

Conclusion: The results of this study suggest that hepatitis C patients having 1 dominant strain in the circulation may show a relatively weaker immune response resulting in lower ALT and higher viremia levels, whereas patients with high degrees of virus quasispecies diversity have higher ALT levels and a more active immune response causing the selection of new genome variants and depressing viral replication partly.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Female
  • Genetic Heterogeneity
  • Genetic Variation*
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Viral Load
  • Viral Proteins / genetics*
  • Viremia

Substances

  • HVR1 protein, Hepatitis C virus
  • Viral Proteins
  • Alanine Transaminase