HEPATITIS-C VIRAL QUASI-SPECIES AND LIVER-DAMAGE IN PATIENTS WITH CHRONIC HEPATITIS-C VIRUS-INFECTION

To clarify the virological differences in patients with chronic hepati tis C virus (HCV) infection with and without liver damage, we assessed HCV markers in 306 patients from a rural area of Japan. Genotypes of HCV RNA were determined by polymerase chain reaction, and levels of RN A were determined by branched DNA signal-amplification assay. All pati ents had undergone annual tests for alanine aminotransferase (ALT) lev els from 1986 to 1995. Patients were categorized into three groups: gr oup A, 121 patients (39.5%) with normal ALT levels on all occasions fo r 10 years; group B, 127 patients (41.5%) with intermittently abnormal AUT levels; and group C, 58 patients (19.0%) with consistently abnorm al ALT levels. There were no significant differences in serum RNA leve ls or distribution of genotypes among the three groups. We selected 10 patients from group A with normal ALT levels and 10 from group C with abnormal levels for sequence analysis of the HCV core region (nt 169- 378) of five clones from each patient. More mutations were found in th e 50 clones from the 10 patients from group C than in the 10 patients from group A. In group A, all mutations were synonymous so that the de duced amino acid sequences were identical among clones from each patie nt, whereas in group C 16 of 57 mutations were nonsynonymous so that t he deduced amino acid sequences showed differences in the five clones of eight of 10 patients. In conclusion, the HCV core region was highly conserved in patients with normal liver biochemical test results but not in those with abnormal results. Our results suggest that abnormal liver biochemical test results in patients with chronic HCV infection may be associated with high degrees of virus quasispecies diversity.