Hepatitis C viral quasispecies and liver damage in patients with chronic hepatitis C virus infection

Jun Hayashi, Yasuhiro Kishihara, Kouzaburo Yamaji, Norihiro Furusyo, Tetsuro Yamamoto, Youngduk Pae, Yoshitaka Etoh, Hideyuki Ikematsu, Seizaburo Kashiwagi

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88 Citations (Scopus)


To clarify the virological differences in patients with chronic hepatitis 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 RNA were determined by branched DNA signal-amplification assay. All patients had undergone annual tests for alanine aminotransferase (ALT) levels from 1986 to 1995. Patients were categorized into three groups: group A, 121 patients (39.5%) with normal ALT levels on all occasions for 10 years; group B, 127 patients (41.5%) with intermittently abnormal ALT levels; and group C, 58 patients (19.0%) with consistently abnormal ALT levels. There were no significant differences in serum RNA levels 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 the 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 deduced amino acid sequences were identical among clones from each patient, whereas in group C 16 of 57 mutations were nonsynonymous so that the 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.

Original languageEnglish
Pages (from-to)697-701
Number of pages5
Issue number3
Publication statusPublished - 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology


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