Bile duct cells and hepatocytes differentiate from the same hepatic progenitor cells. To investigate the possible association of viral hepatitis B and C with intrahepatic cholangiocarcinoma (ICC), we conducted a retrospective case -control study using univariate and multivariate logistic analyses to identify risk factors for ICC. Besides hepatic lithiasis (25.6%; Po0.001), seropositivity for hepatitis B surface antigen (37.5% of all ICC patients; odds ratio (OR) ¼ 4.985, Po0.001) and seropositivity for hepatitis C antibodies (13.1%; OR ¼ 2.709; P ¼ 0.021) are the primary independent risk factors for ICC. Cirrhosis exerted synergic effects on the development of ICC. We compared the age distributions of viral-hepatitis associated ICC to that of viral hepatitis-associated hepatocellular carcinoma (HCC). The mean age of ICC patients with viral hepatitis B (56.4 ± 11.1 years) were 9 years younger than that of ICC patients with viral hepatitis C (65.6 ± 9.17 years), similar to that observed in HCC. The incidence ratio of HCC : ICC : CHC (combined hepatocellular cholangiocarcinoma) in our population was 233 : 17 : 1 consistent with the theoretic ratio of hepatocyte number to cholangiocyte number in the liver. Our findings indicated that both viral hepatitis-associated ICC and HCC shared common disease process for carcinogenesis and, possibly, both arose from the hepatic progenitor cells.

The presence of sudden-onset abdominal pain is the only independent indicator of ruptured HCC. Hepatic resection, when feasible, is the treatment of choice and can result in an overall survival rate comparable to that of patients with non-ruptured HCC.

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The hepatitis B virus (HBV) core protein has been found in the nucleus, the cytoplasm, or both of HBVinfected hepatocytes. However, the mechanism that regulates the subcellular localization of the HBV core protein is still unclear. In this report, we demonstrate that nuclear localization of the HBV core protein is cell cycle-regulated in two different cell lines. The amount of the core protein in the nucleus was increased during the G, phase, reduced to an undetectable level during the S phase, and increased again when the cells were confluent and ceased to grow. Thus, the nuclear localization of the core protein during HBV infection can be at least partially attributed to liver injury and regeneration, which cause the hepatocytes to enter cell cydes. Based on the observation that the cytoplasmic core protein was phosphorylated and the nuclear core protein was not, we speculate that nuclear localization of the HBV core protein is negatively regulated by phosphorylation during the cell cycle.Hepatitis B virus (HBV) can cause acute and chronic hepatitis in humans and is also the major cause ofliver cancer. The HBV core protein, also named core antigen, is the major capsid protein of the virus and is an important serological marker for diagnosis of HBV infection. This antigen has been found in the nucleus, the cytoplasm, or both of hepatocytes infected by HBV (1-3). Although it has been demonstrated that the carboxyl-terminal arginine-rich domain of the core protein contains a signal for nuclear localization (4, 5), the mechanism that regulates the nuclear localization of the core protein is still unclear.We have studied the subcellular localization of the HBV core protein in two different cell lines and report here our results which indicate that nuclear localization of the core protein is cell cycle-regulated. Further studies indicate that this regulation may be mediated by phosphorylation of the core protein. core (8) into the HindIII-Xba I polylinker site of the pRC/ CMV vector (Invitrogen, San Diego). The 1.7-kb pECE-C DNA fragment used in the construction contained the coding sequence of the HBV core protein (adw subtype). In pCMVcore, the expression of the HBV core protein is under the control of the CMV IE promoter. MATERIALS AND METHODSCell Cycle Synchronization. Cells (6 x 105) were plated in a 60-mm Petri dish the day before the synchronization experiment. For synchronization with the serum-free medium, cells were incubated in Dulbecco's modified Eagle's medium (DME medium) without serum for 30 h. This resulted in synchronization of cells in the Go phase of the cell cycle.The cell cycle was then initiated with DME medium containing 20% (vol/vol) calf serum. For synchronization with aphidicolin, cells were incubated with DME medium containing 10% calf serum and 2 ,g of aphidicolin per ml for 48 h. This resulted in synchronization of cells in the late G1 phase. The cells were either analyzed at this time point or allowed to enter the S phase by further incubation in the same medium without aphidico...

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These results suggest a weak association between HCV and thyroid autoimmunity in females. As in the ordinary population with thyroid autoantibodies, they should be evaluated for thyroid status and be followed-up if thyroid autoimmunity is evident. However, seropositivity of thyroid autoantibodies is not a contraindication to interferon therapy.