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The core protein of hepatitis C virus (HCV) has been implicated in hepatocarcinogenesis. In order to determine whether there is a correlation between mutations of the core protein and the development of hepatocellular carcinoma (HCC), the core protein-coding sequence of the viral genome of HCV subtype 1b (HCV-1b) obtained from patients with and without HCC was analyzed. We found that 12 (40.0%) of 30 HCV-1b isolates from patients with HCC but none of 29 isolates from patients without HCC had a point mutation(s) in an N-terminal region of 20 residues. Similarly, 10 (33.3%) of 30 isolates from patients with HCC had mutations in a limited region between residues 141 and 160, whereas only 2 (6.9%) of 29 isolates from patients without HCC did. The differences between the two groups were statistically significant. The mutations were found in isolates from both cancerous and adjacent noncancerous tissues of patients with HCC, suggesting that the mutations were present before the development of HCC. The other regions of the core protein of some isolates also had mutations, but no significant difference was observed between isolates from patients with HCC and those from patients without HCC. The F protein, a frameshift product that is still hypothetical for HCV-1b strains, showed more sequence diversity than the core protein among the isolates analyzed, but there were no significant differences in the mutation rates or positions between isolates from patients with HCC and isolates from patients without HCC, except for a short N-terminal sequence of ϳ11 residues that is shared with the core protein.Hepatitis C virus (HCV) is a major etiologic agent of chronic hepatitis worldwide, with the estimated number of infected individuals being more than 170 million. It is estimated that 15 to 20% of chronically infected individuals undergo liver cirrhosis in a decade or so after infection, with hepatocellular carcinoma (HCC) arising from cirrhosis at an estimated rate of 1 to 4% per year (14). Although the precise mechanism is yet to be clarified at the molecular level, the HCV core protein is implicated in the hepatocarcinogenesis. For example, it was reported that the HCV core protein rendered cells more resistant to apoptosis (16, 21) and promoted ras oncogenemediated transformation of cultured rodent cells (4, 22, 31). Moreover, transgenic mice expressing the HCV core protein in the liver developed HCC (18).The HCV genome exhibits a considerable degree of sequence variation, and on the basis of these variations, HCV is classified into at least six genotypes and more than 60 subtypes (5, 17, 24). HCV subtype 1b (HCV-1b) is the most prevalent subtype in most parts of Asia including Japan (5,8,12) and is likely more frequently associated than the other HCV subtypes with poor responsiveness to interferon treatment, rapid disease progression, and development of HCC (3,20,29). In addition to the differences at the genotype and subtype levels, other important sequence diversities have been postulated even among isolates of a given su...

The NS3 protein of hepatitis C virus subtype 1b (HCV-1b) isolates obtained from 89 patients with hepatocellular carcinoma (HCC) and 78 patients without HCC were analyzed. On the basis of the secondary structure of the amino-terminal 120 residues of NS3, HCV-1b isolates were classified into group A, group B, and an indeterminate group, each of which was further divided into a number of subgroups, such as A1-1, A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, B2-2, C-1, C-2, and C-3. HCV-1b isolates of subgroup B1-1 were found in 53 (59.6%) of 89 patients with HCC and 19 (24.4%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.00001). Although the number of isolates was small, subgroup B2-1 was also highly associated with HCC, with all five isolates in that subgroup being found in patients with HCC (P < 0.05). On the other hand, HCV-1b isolates of subgroup A1-1 were associated only weakly with HCC; they were found in 6 (6.7%) of 89 patients with HCC and in 25 (32.1%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.0001). The other subgroups, such as A1-2, A2-1, B1-2, C-1, C-2, and C-3, were moderately associated with HCC; their distribution patterns among patients with HCC did not differ significantly from those among patients without HCC. Taken together, our results suggest that HCV-1b isolates of subgroups B1-1 and B2-1 are highly associated with HCC and that this secondary structure analysis may be useful for predicting the relative risk of developing HCC.Hepatitis C virus (HCV) easily establishes chronic persistent infection, initially causing chronic hepatitis, followed by liver cirrhosis, from which hepatocellular carcinoma (HCC) arises at an estimated rate of 1 to 4% per year (17). However, it is still a matter of debate whether all HCV strains are associated with HCC to the same extent. The HCV genome exhibits a considerable degree of sequence variation, and HCV is presently classified into at least six genotypes and more than 60 subtypes (5,22,27). HCV subtype 1b (HCV-

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Non-neoplastic tumor-like lesions in the pancreas are uncommon. Here, we present a case of multiple solid pancreatic hamartomas in a 78-year-old Japanese woman. Her computed tomography revealed a pancreatic mass, measuring 1.8 cm in maximum diameter. However, no symptoms were found. She was not an alcoholic and had no history of pancreatitis. The patient underwent a pancreatoduodenectomy, and three well-demarcated solid nodules measuring 1.7 cm, 0.4 cm, and 0.3 cm in diameter were found in the pancreatic head. Microscopically, the lesions were composed of non-neoplastic, disarranged acinar cells and ducts embedded in a sclerotic stroma with elongated spindle cells that lacked discrete islets. The stromal spindle cells were immunoreactive for C�34 and C�117. The histological diagnosis was multiple solid hamartomas of the pancreas. There has been no recurrence 30 mo after surgery. So far, 18 cases of pancreatic hamartoma have been reported in the English literature, including our case. Six out of these 18 cases seemed to fit the criteria of solid pancreatic hamartoma. Although the number of cases was limited, solid pancreatic hamartomas seem to be benign tumor-like lesions, which are found incidentally in healthy middle-aged adults, but occasionally involve the whole pancreas, resulting in a poor prognosis. Solid pancreatic hamartoma was sometimes associated with minor pancreatic abnormality, and multiple small lesions other than the main tumors were detected in a small number of cases. From these findings, one may speculate that solid pancreatic hamartoma could be the result of a malformation during the development of the pancreas.