PHYLOGENETIC ANALYSIS OF HEPATITIS-C VIRUS ISOLATES AND THEIR CORRELATION TO VIREMIA, LIVER-FUNCTION TESTS, AND HISTOLOGY

Nucleotide sequence analysis of hepatitis C virus (HCV) strains showed substantial variability leading to a classification into several geno types and subtypes. The data correlating HCV genotypes and subtypes wi th hepatitis C viremia levels, demographic characteristics of patients (age, mode of transmission, duration of infection), and severity of l iver disease are conflicting, The interpretation of several studies is further complicated because the molecular methods used lacked specifi city for genotyping/subtyping and underestimated viremia levels, espec ially in patients infected with HCV genotypes 2 and 3, In the present study we investigated 97 consecutive patients with chronic hepatitis C using molecular ''gold standard'' methods, HCV subtyping was performe d by sequence and phylogenetic analysis of the nonstructural (NS)-5 re gion and serum HCV-RNA concentration was assessed by a validated genot ype-independent quantitative reverse-transcription-polymerase chain re action assay using an internal RNA standard, Patients infected with su btypes HCV-1b, HCV-2a-c, and HCV-4 were older than patients infected w ith HCV-1a and HCV-3a, Serum HCV-RNA levels ranged from 1.5 x 10(4) to 1.0 x 10(8) copies/mL with no significant differences between median serum HCV-RNA concentrations in patients infected with different genot ypes/subtypes, Although patients infected with HCV-1b were older, no b iochemical or histological evidence was obtained that this subtype is associated with more severe liver disease, Furthermore, the present st udy showed a lack of correlation between the serum HCV-RNA concentrati on, biochemical parameters, and liver histology, The median serum HCV- RNA levels in patients with chronic persistent hepatitis, chronic acti ve hepatitis, and liver cirrhosis were 5.0 x 10(6) copies/mL, 2.5 x 10 (6) copies/mL, and 5.0 x 10(6) copies/mL, respectively, These differen ces were not significant, In conclusion, using optimized and validated molecular techniques, the present cross-sectional study showed no cor relation between HCV genotypes/subtypes, viremia, liver function test results, and histology.