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The presence of the "Japanese type" NS4 region was investigated in two 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 diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification 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. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NS4-negative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type II, whereas in NS4-negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and -negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative, descriptive study on the prevalence of hepatocellular carcinoma either associated or not with cirrhosis was undertaken between the cities of Trieste, Italy, and Chiba, Japan. Data were derived from 12,340 and 2,052 autopsies consecutively performed in Trieste and Chiba during 1980 to 1984 and 1975 to 1985, respectively. During these years, more than 70% of all deaths were studied by autopsy in Trieste. Clinical cases of hepatocellular carcinoma admitted to the Chiba University Hospital were also analyzed to correct for the bias induced by the relatively small number of autopsies in Chiba. Serum hepatitis B surface antigen was more frequent in Chiba, whereas alcohol intake was greater in Trieste. From the comparison of the data, we conclude: (i) hepatocellular carcinoma was associated with cirrhosis in the large majority of the cases both in Trieste (87%) and Chiba (81%); (ii) in both sexes, the average age of hepatocellular carcinoma patients was significantly older (p less than 0.005) in Trieste than in Chiba; (iii) in the autopsy series, cirrhosis was more frequent in Trieste (9.7%) than in Chiba (1.5%); (iv) in Chiba, hepatocellular carcinoma was more frequent than cirrhosis not complicated by hepatocellular carcinoma (6.9 vs. 1.5%) at necroscopy, and (v) the age-standardized rate of hepatocellular carcinoma was significantly (p less than 0.01) higher in Trieste than in Chiba. These geographical differences might be related to the different type of cirrhosis observed in Trieste (alcoholic) and Chiba (postnecrotic).