To clarify the relationship between hepatitis C virus infection and the development of hepatocellular carcinoma as sequelae of non-A, non-B posttransfusion hepatitis, 231 patients with chronic non-A, non-B hepatitis (96 with chronic hepatitis, 81 with cirrhosis and 54 with hepatocellular carcinoma) were analyzed for antibody to hepatitis C virus and were compared with 125 patients with chronic hepatitis B (50 with chronic hepatitis, 46 with cirrhosis and 29 with hepatocellular carcinoma). Antibody to hepatitis C virus was detected in 89.6%, 86.4% and 94.4% of patients with non-A, non-B hepatitis-related chronic hepatitis, cirrhosis and hepatocellular carcinoma, respectively, compared with 6%, 17.4% and 34.5% with similar diseases related to hepatitis B. A history of transfusion was documented in 52%, 33% and 42% of anti-hepatitis C virus-positive cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The mean intervals between the date of transfusion and the date of diagnosis of anti-hepatitis C virus-positive chronic hepatitis, cirrhosis and hepatocellular carcinoma were 10, 21.2 and 29 yr, respectively. In 21 patients with transfusion-associated hepatocellular carcinoma, anti-hepatitis C virus was present in each serial sample available for testing, including samples obtained up to 14 yr before the diagnosis of hepatocellular carcinoma. These data suggest the slow, sequential progression from acute hepatitis C virus-related non-A, non-B hepatitis through chronic hepatitis and cirrhosis to hepatocellular carcinoma and support a causal association between hepatitis C virus and hepatocellular carcinoma.

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SummaryTo clarify the role of c-Mpl ligand (thrombopoietin: TPO) in liver cirrhosis (LC), we examined serum TPO levels (sTPO) in patients with LG (N = 44), chronic hepatitis (CH; N = 13) and healthy controls (N = 41) by an enzyme-linked immunosorbent assay. Although platelet counts of all LC patients (89 ± 59 × 109/1; mean ± SD) were lower than those of controls and CH patients, sTPO levels in LC patients (1.23 ± 0.51 fmol/ml) were the same as those in controls (1.22 ± 0.37) and CH patients (1.18 ± 0.36). Platelet counts were significantly higher in splenectomized patients than in unsplenectomized patients, but the sTPO level did not differ between these two groups. In LC patients, the sTPO level was not correlated with the platelet count, but was correlated with prothrombin time, activated partial thromboplastin time, and total bilirubin, indicating that production of TPO in the liver decreases slightly with the development of liver dysfunction. Our findings suggest that production of TPO is maintained in LC patients and their thrombocytopenia is not due to a defect in platelet production.

This study was conducted to clarify if the long-term histological outcome among patients with chronic hepatitis C differs according to whether they are infected with genotype 1 or 2 hepatitis C virus (HCV). We examined 140 patients with chronic hepatitis C. The HCV genotype was determined by the enzyme-linked immunosorbent assay (ELISA) based on genotypes 1 and 2 specific recombinant proteins; genotype 1 was found in 100 patients (96 were 1b and 4 were indeterminate) and genotype 2 in 36. The two groups showed no significant difference for any clinical background features. Deterioration of the grade of liver histology during the follow-up period was seen in 68.0 percent of the patients with genotype 1 as compared with 41.7 percent of those with genotype 2 (P < .01). Similarly, the deterioration of the stage of liver histology was more common in the former group than in the latter (63.0 percent and 38.9 percent respectively; P < .05). The mean serum HCV-RNA titer was significantly higher in the patients with genotype 1 than in those with genotype 2 (P < .001), and multivariate analysis showed the titer was one of the independent factors of the deterioration of the stage (P = .0044). This phenomenon may be related in part to the difference in pathogenicity between the two HCV genotypes. In conclusion, our results suggest that more severe progression of chronic hepatitis C is seen in patients showing genotype 1b compared with those with genotype 2.

To document the transmission of hepatitis C virus (HCV) through needlestick accidents, 3 health workers who acquired HCV through such accidents and their HCV donor patients were studied using molecular evolutionary analysis based on the HCV E2 region. At least six clones were sequenced from each subject. Nucleotide substitutions were estimated by the six-parameter method, and a phylogenetic tree was constructed by the neighbor-joining method. HCV isolates from the donor patient and the recipient were nested in one monophyletic cluster; this clustering was confirmed to be statistically significant by bootstrap analysis. The nucleotide divergence among the isolates from the recipient was always smaller than that from the donor, supporting the notion that the direction of transmission was from the donor to the recipient. These findings provide evidence, at a molecular evolutionary level, that HCV was transmitted through needlestick accidents.