DIFFERENT GENOTYPES OF HEPATITIS-C VIRUS ARE ASSOCIATED WITH DIFFERENT SEVERITY OF CHRONIC LIVER-DISEASE

The presence of the ''Japanese type'' NS4 region was investigated in t wo series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnos is, and serum aminotransferase activities. Genomic amplification was c arried out by ''nested'' polymerase chain reaction (PCR) with a pair o f primers synthesized according to the sequence of JK-l isolated in Ja pan. The presence of viral replication was confirmed further by PCR am plification of the 5'NC region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. N S4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each g roup. Cirrhosis was significantly (P < 0.0007) more common in NS4-posi tive than in NS4-negative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infe cted by Type II, whereas in NS4-negative patients all four genotypes w ere present though Type II still constituted the majority. Cirrhosis w as associated exclusively with Type II both in NS4-positive and -negat ive subjects. These data indicate that, although the positivity for NS 4 ''Japanese'' region seems to be associated with a more aggressive li ver disease, the most prevalent Type II predicts more specifically tho se who are likely to develop cirrhosis. Since the same findings were o btained in two population from different areas of the world, the genot ype of HCV appears to be one of the major determinants of the progress ion of chronic active hepatitis to cirrhosis. (C) 1994 Wiley-Liss, Inc .