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BACKGROUND One of the major morphologic characteristics of hepatitis B is a hepatocellular regeneration which is induced by massive hepatocyte necrosis and associated with proliferative activity of hepatocytes. The purpose of this study is to document the proliferative activity of hepatocytes in various types of hepatitis B by immunohistochemical staining for proliferative cell nuclear antigen-labelling index (PCNA-LI) and electron microscopy. METHODS We studied 83 patients with hepatitis B: 11 cases of acute viral hepatitis, 24 cases of mild chronic hepatitis, 34 cases of severe chronic hepatitis with early cirrhosis and 14 cases of severe chronic hepatitis. The PCNA was tested by immunohistochemical staining using anti-PCNA antibody. Furthermore we evaluated the ultrastructure of acinus-forming hepatocytes (AFH) by electron microscopy. RESULTS The expression rate and labelling index of PCNA were 27.3% and 5.3 +/- 0.9% in acute viral hepatitis, 62.5% and 22.9 +/- 31.7% in mild chronic hepatitis, and then 47.1% and 14.1 +/- 24.2% in severe chronic hepatitis with early cirrhosis, respectively (Figure 1). By contrast, no detectable PCNA expression was noted in AFH. Electron microscopic findings showed that hepatocytes forming a rosette underwent marked degenerative changes with sinusoidal capillarization and increased fine strands of collagen fiber in portal area. CONCLUSION The proliferative activity of hepatitis B was significantly decreased in severe chronic hepatitis containing AFH. This result suggested that differences in proliferative activity was associated with hepatic cell necrosis and AFH.

Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment. Two HCV isolates with NS5A2209-2248 mutations from HCC patients were intermediate type. These results do not support that the NS5A2209-2248 determines interferon sensitivity of HCV-1b and that the mutations is associated with development of HCC.

This study investigated the clinical variables that predict hepatitis B e antigen (HBeAg) loss in lamivudine-resistant patients receiving adefovir therapy.Fifty-six consecutive HBeAg-positive patients treated with adefovir for at least 12 months were enrolled in this study. All had serum alanine aminotransferase (ALT) levels over twice the upper limit of normal (ULN) as a result of lamivudine resistance. Predictors of HBeAg loss after switching from lamivudine to adefovir were examined.During the follow-up period, 18 (32.1%) of 56 patients showed a loss of HBeAg. The estimated rates of HBeAg loss at 6, 12, and 18 months were 11.5%, 26.8%, and 42.9%, respectively. Univariate analysis revealed that pretreatment ALT levels10 x ULN (P = 0.029), a viral load at 3 months of therapy (P = 0.017), and viral decline by3 log(10) from baseline at 3 months (P0.001) were significantly associated with the loss of HBeAg within 12 months of therapy. With multivariate analysis using the stepwise logistic regression model, pretreatment ALT10 x ULN (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.09-19.44; P = 0.044) and viral suppression3 log(10) at 3 months (OR, 10.39; 95% CI, 1.86-58.07; P = 0.008) were identified as the two independent predictors of HBeAg loss.Pretreatment ALT levels and the initial pattern of post-treatment viral decline are the strongest predictors of the early achievement of HBeAg loss following treatment with adefovir in lamivudine-resistant patients. These results may provide useful information for the optimal timing of adefovir rescue as well as for better monitoring after treatment.

Purpose: Hepatocellular carcinoma (HCC) invading the portal vein is a medical challenge. We evaluated the therapeutic efficacy of a combination of transarterial and systemic chemo-infusion for large HCC with portal vein thrombosis (PVT) compared with conservative management. Patients and methods: This was a case-control cohort study of 103 consecutive patients with Child-Pugh class A who had a large (>10 cm) HCC with PVT. The patients were assigned to receive either combined transarterial epirubicin (50 mg/m2) plus cisplatin (60 mg/m2) chemo-lipiodolization and systemic 5-fluorouracil (200 mg/m2) chemo-infusion (ECF regimen) at monthly intervals (n=80) or conservative management (n=23). Results: The objective tumor response (21.3 vs. 0%, P=0.011) and overall survival (8.7 vs. 3.5 months, P

Drug resistance remains a major problem during lamivudine treatment for patients with hepatitis B virus infection. Continuing or stopping lamivudine in patients with biochemical breakthrough is an issue that has not been investigated extensively. Particularly, HBeAg seroconversion and its durability achieved in these settings have never been studied so far. In this study, we compared the clinical outcomes including HBeAg seroconversion in hepatitis B e antigen (HBeAg)-positive patients who either continued or stopped lamivudine treatment after biochemical breakthrough. This was a retrospective cohort study of 73 consecutive patients with biochemical breakthrough followed up for at least 12 months. Of these, 35 (Group I) stopped and the remaining 38 (Group II) continued lamivudine therapy after breakthrough. During 12 months, there was a tendency towards higher rates of HBeAg seroconversion in Group I compared with Group II (P = 0.078). By multivariate analysis, age ≥45 years and acute exacerbation within 6 months of stopping lamivudine were the two independent predictors of HBeAg seroconversion for Group I (P = 0.034 and P = 0.012, respectively). There was no difference in the overall incidence of acute exacerbation and hepatic decompensation between the two groups (P = 0.333 and P = 0.555, respectively). Six patients (17.1%) in Group I developed hepatic decompensation, for which bilirubin ≥1.2 mg/dl was an independent predictor (P = 0.002). The therapeutic gain in continuing lamivudine for biochemical breakthrough is questionable. This study suggests that discontinuation of lamivudine may be an option in older patients with normal bilirubin level. J. Med. Virol. 77:367–373, 2005. © 2005 Wiley-Liss, Inc.

fistula resulting from migration of a biliary stent: a case report. Gastrointest Endosc 1998;48:80-3. 12. Yoshida EM, Steinbrecher UP. Abdominal pain and rectal bleeding as a complication of biliary stent migration in a liver transplant recipient. Gastrointest Endosc 1998;47:418-20. 13. Liebich-Bartholain L, Kleinau U, Elsbernd H, Buchsel R. Biliary pneumonitis after proximal stent migration. Gastrointest Endosc 2001;54:382-4. 14. Tan CC, Hall RI, Pallan JP, Irons RP, Freeman JG. Transhepatic proximal migration of percutaneous-endoscopic biliary stent presenting as an abdominal wall abscess. Gastrointest Endosc 1996;43:152-4. Brief Reports B-I Lee, B-W Kim, H Choi, et al.

E-cadherin is involved in intercellular binding and cellular polarity formation. beta-catenin plays a fundamental role in regulation of the E-cadherin cell adhesion complex. The abnormalities of the components of the complex may disrupt this adhesive function. We investigated the expression patterns of E-cadherin and beta-catenin to determine the clinical significance of these proteins in hepatocellular carcinoma.Thirty-six hepaticellular carcinoma tissues and adjacent non-tumor specimens were analyzed. Subcellular distribution of E-cadherin and beta-catenin was examined by immunohistochemistry staining. We evaluated the patterns of the expression, and investigated the relationship with the cause of HCC; level of AFP; TNM stage; tumor size; growth types; metastasis; differentiation grade of HCC; and presence of portal vein thrombosis.Immunohistochemistry showed that all non-tumor tissues had membranous type staining of E-cadherin. All non-tumor tissues showed cytoplasmic type staining of beta-catenin, but no beta-catenin accumulation in nuclei was found. 58% (21/36) of HCC showed positive expression of E-cadherin in cytoplasmic membrane. The cytoplasmic expression of beta-catenin in HCC was 83% (30/36); nuclear expression in 14% (5/36); and no staining in 3% (1/36). Nuclear beta-catenin expression was observed in none (0/4) of the well-differentiated HCC; 17%(3/9) of moderate-differentiated HCC; and 17%(2/6) of poorly-differentiated HCC. There were no relationships between E-cadherin and beta-catenin expression with other clinicopathologic factors.Loss of cytoplasmic staining of E-cadherin and nuclear accumulation of beta-catenin were observed in HCC. Nuclear accumulation of beta-catenin was not found in well differentiated HCC but was found in poorly differentiated HCC.

This study was designed to clarify the fine structures of the hepatocytes and mesenchymal tissues in chronic hepatitis according to severity.For the purpose of elucidating the ultrastructural characteristics of mesenchymal tissues, liver biopsy specimens were studied by light and electron microscopy in 20 patients with chronic hepatitis.1) Hepatocytes in mesenchymal tissues were thought to be in the stage of regenerated or degenerated process. 2) Regenerating nodules were surrounded by a basement membrane-like materials in the space of Disse. 3) In the widened Disse space the deposition of collagen fiber bundles and increased numbers of hepatic stellate cells in necrotic area were observed. 4) In necrotic areas, hepatic mesenchymal cell response including an increase of collagen fibers and fibroblast, angiogenesis, and a proliferation of bile ductules were also observed.These observations suggest that the fibrosis in severe chronic hepatitis was accompanied by the mesenchymal response including the proliferation of hepatic stellate cells, fibroblasts, capillarization of Disse space, and mesenchymal proliferation. Finally, this fibrosis observed electron microscopically may be a cause of functional hepatic failure.