VARIATIONS IN THE HYPERVARIABLE REGION-1 OF THE ENVELOPE REGION E2 OFHEPATITIS-C VIRUS RNA APPEAR ASSOCIATED WITH VIRUS PERSISTENCE INDEPENDENTLY OF LIVER-DISEASE

The high genetic variability of the 5' end of the envelope protein-cod ing region E2 (HVR1 E2) of Hepatitis C Virus (HCV) RNA has been sugges ted by many authors to play an important role in both virus persistenc e and outcome of liver disease. We studied the relations between HVR1 E2 variability and HCV genotypes, HCV-RNA levels and liver disease in 8 chronic HCV carriers (5 males and 3 females, median age 41 years, fo llowed-up for a mean period of 3 years), Four were healthy HCV carrier s with persistently normal ALT levels and normal liver histology and 4 patients with chronic liver disease. In each patient, the HVR1 E2 var iability of 2 serum HCV-RNA isolates obtained at least 12 months apart were evaluated by direct sequencing, Nucleotide and amino acid homolo gies ranged between 97.6%-57.1% and 92.8%-25% in healthy carriers and 95.2%-55.9% and 89.3%-32.1% in patients, respectively, We did not obse rve any correlation between HVR1 E2 heterogeneity and HCV genotypes, v iraemia levels, presence and extent of liver necroinflammation. Our fi ndings suggest that HVR1 E2 heterogeneity has no direct implications i n hepatitis, pathogenesis but it could play a major role in virus pers istence.