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


CONCLUSIONS
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.
Bozdayi
A M
AM
Institute of Hepatology, Ankara University School of Medicine, Ankara, Turkey. bozdayi@pallas.dialup.ankara.edu.tr
Uzunalimoglu
O
O
Aslan
N
N
Bozkaya
H
H
Türkyilmaz
A R
AR
Kayhan
B
B
Sahin
T
T
Sivri
B
B
Uygun
A
A
Altiok
A
A
Cetinkaya
H
H
Karayalçin
S
S
Yurdaydin
C
C
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D005260:Female; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*; D014766:Viremia
C400562:HVR1 protein, Hepatitis C virus; D014764:Viral Proteins; D000410:Alanine Transaminase