DEGREE OF DIVERSITY OF HEPATITIS-C VIRUS QUASI-SPECIES AND PROGRESSION OF LIVER-DISEASE

We examined the quasispecies of the hepatitis C virus genome in 28 pat ients with liver disease of varying severity. Nucleotide sequences of the hepatitis C virus genome spanning the region from the core to enve lope were used to calculate the nucleotide diversity: 0.58% +/- 0.88% in 5 patients with acute hepatitis, 0.85% +/- 0.62% in 5 patients with chronic persistent hepatitis, 1.79% +/- 0.92% in 11 patients with chr onic active hepatitis, 3.05% +/- 1.26% in 4 patients with cirrhosis an d 2.71% +/- 1.47% in 3 patients with cirrhosis complicated by hepatoce llular carcinoma. Thus the intrapatient variation in nucleotides incre ased significantly with severity of liver disease (p < 0.01), except i n those cases of cirrhosis complicated by hepatocellular carcinoma. Mu ltivariate analysis including the histology, duration of infection, ag e, sex, history of blood transfusion and serum level of ALT at diagnos is as variables showed that the histological finding was the strongest independent factor of the nucleotide diversity (p = 0.003). Serial an alysis of the genome in three patients demonstrated that the intrapati ent variation in nucleotides increased with the progression of liver d isease. The magnitude of the intrapatient variation in nucleotides ded uced from the observed changes in the patients was correlated with the mean serum levels of ALT. These findings suggest that the degree of d iversity of HCV quasispecies is related to the progression of liver di sease.