Animals ; Apoptosis ; Carcinoma, Hepatocellular ; pathology ; virology ; Cell Line, Tumor ; Cell Proliferation ; Hepatitis B virus ; Hepatocytes ; pathology ; virology ; Humans ; Liver Neoplasms ; pathology ; virology ; Trans-Activators ; genetics ; metabolism ; physiology

Subcellular localizaton of HBcAg have been found to be related to the activity of liver disease and HBV replication. The aim of this study was to determine whether the degree of expression of HBcAg in the hepatocyte nucleus and cytoplasm reflects the level of viral replication and histological activity in chronic HBV infection. A total of 102 patients with biopsy proven chronic hepatitis B were included. There was a highly significant correlation between the levels of HBV DNA in serum and the degree of expression of HBcAg in the nucleus for HBeAg-positive(p=0.000) and negative patients(p=0.04). There was a highly significant, correlation between the degrees of expression of HBcAg in hepatocyte cytoplasm and histologic activities (p<0.01) for HBeAg-positive patients. The degrees of expression of HBcAg in the hepatocyte cytoplasm correlated positively with the lobular activities (p<0.01), but not correlated with the portal activity and fibrosis for HBeAg-negative patients. In conclusion, in the young patients with chronic B viral hepatitis, the degree of expression of HBcAg in the hepatocyte nucleus may affect viral load, and the degree of expression of HBcAg in the hepatocyte cytoplasm may affect histologic activities of liver disease.
Male ; Liver/pathology/virology ; Humans ; Hepatocytes/pathology/*virology ; Hepatitis B, Chronic/*pathology/*virology ; Hepatitis B e Antigens/metabolism ; Hepatitis B Core Antigens/*metabolism ; DNA, Viral/blood ; Cytoplasm/virology ; Cell Nucleus/virology ; Adult ; Adolescent

No abstract available.
Biopsy, Fine-Needle ; Hepatitis B virus ; Hepatitis B, Chronic/*complications ; Hepatocytes/*pathology ; Humans ; Liver Cirrhosis/diagnosis/*pathology/virology ; Risk Factors

Apoptosis ; drug effects ; Hepatocytes ; pathology ; virology ; Humans ; Liver Neoplasms ; pathology ; virology ; Mutation ; Plasmids ; genetics ; Trans-Activators ; genetics ; pharmacology ; Transfection ; Tumor Cells, Cultured

OBJECTIVETo investigate the effects of hepatitis C virus (HCV) on transcription regulation genes of host cells by gene chip assays in cultured cells with intact HCV genome.

METHODSHuh-7 hepatoma cells were cultured and infected with in vitro constructed HCV. The total RNAs, proteins and cell culture supernatants of HCV infected cells and control cells were isolated. Proteins and cell culture supernatants were used to detect the HCV replication and protein expression in cell culture system. The HCV protein expression was detected with Western blotting. Released HCV from infected cells was analyzed by real-time fluorescence quantitative PCR. Total RNA was qualified using 10 g/L agarose gel electrophoresis. cRNA was synthesized, fluorescence labeled and purified, then hybridized with Agilent oligo microarray (20173 probes). Differential expression of genes related to transcription in cell culture system was analyzed.

RESULTHCV was positive in cell culture supernatants and HCV protein expression was also positive according to Western blotting results. Eleven up-regulated and 11 down-regulated genes related to transcription were found after Agilent gene chip screening.

CONCLUSIONIntact hepatitis C virus cell culture system provides an useful tool for study on the affects of HCV infection on transcription regulation genes in host cells.

Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome, Viral ; Hepacivirus ; genetics ; growth & development ; Hepatocytes ; virology ; Humans ; Liver Neoplasms ; genetics ; pathology ; virology ; Transcription, Genetic

BACKGROUND/AIMS: This study was designed to clarify the fine structures of the hepatocytes and mesencymal tissues in chronic hepatitis according to severity. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.
Adult ; English Abstract ; Female ; Hepatitis, Chronic/*pathology/virology ; Hepatitis, Viral, Human/*pathology ; Hepatocytes/ultrastructure ; Human ; Liver/*ultrasonography ; Male ; Mesoderm/ultrastructure ; Microscopy, Electron ; Middle Aged

OBJECTIVETo detect p24 antigen of human immunodeficiency virus (HIV)-1 in the liver biopsy specimens of patients with HIV infection.

METHODSLiver biopsy samples from 14 patients with HIV/AIDS (11 man, 3 women; age range 27-52 years; infection time range 8-13 years) were examined by immunohistochemistry prospectively.

RESULTSIntracellular expression of HIV-1 p24 antigen was detected in Kupffer cells, endothelial cells and hepatocytes. There were more HIV-positive liver cells in the patients with severer liver damage than those with milder liver damage (t=2.5189, P=0.0270).

CONCLUSIONThese findings indicate that HIV-1 could replicate in the liver of HIV-infected patients and might be related to the liver cells apoptosis.

Adult ; Female ; HIV Core Protein p24 ; biosynthesis ; HIV Infections ; metabolism ; virology ; HIV-1 ; physiology ; Hepatocytes ; metabolism ; pathology ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; Liver ; metabolism ; pathology ; virology ; Male ; Middle Aged

OBJECTIVETo study the expression of HBsAg and HBcAg in hepatocytes in CHB patients, and analyze the correlation among the expression of HBsAg and HBcAg, the quantity of HBV DNA in serum, the pathology of liver tissue and the clinical manifestation.

METHODSQuantitative polymerase chain reaction was used to assay the quantity of HBV DNA in serum in 351 CHB patients. Furthermore pathological diagnosis was performed using liver biopsy to assay the expression of HBsAg and HBcAg in hepatocytes by an immunohistochemical staining technique.

RESULTSThe positive expression rate of HBsAg and HBcAg in hepatocytes was 92.3% and 76.9% respectively. Cytoplasm-membrane HBcAg expression type (75.6%) was observed in the CHB with more active inflammation, while Nucleus HBcAg expression type (24.4%) was observed in the CHB with more sedative one (P < 0.0001). The expression of HBsAg was correlated with the quantity of HBV DNA in serum (rp = 0.24, P = 0.0129), while inversely correlated with the inflammation and the fibrillation of liver tissue (rp = -0.22, P = 0.0279; rp = -0.23, P = 0.0186). The expression of HBcAg was correlated with the quantity of HBV DNA in serum (rp = 0.52, P < 0.0001), while was inversely correlated with the inflammation and the fibrosis of liver (rp = -0.33, P < 0.0001; rp = -0.34, P < 0.0001).

CONCLUSIONCytoplasm-membrane HBcAg expression type was observed in the CHB with more active inflammation, while Nucleus HBcAg expression type was observed in the CHB with mild change. In the immunopathogenesis of the liver damage in CHB, HBcAg might be a main target antigen. HBsAg might be a sensitive index to screen HBV infection; HBcAg might probably be a reliable index to evaluate the replication of HBV

Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; analysis ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Hepatocytes ; virology ; Humans ; Immunohistochemistry ; Liver ; pathology ; Male ; Middle Aged

Hepatitis C virus (HCV) is a major causative agent in liver disease. In order to investigate if Korean type HCV core protein and its related mutants, S99Q and S116I, are cytopathic to liver, three types of transgenic mice were established. The expression of transgenes was confirmed by HCV specific RT-PCR and Western immunoblotting. The livers of all wild type core and S116I transgenic lineages remained largely histologically normal. However, the livers of the S99Q transgenic mice showed significant high level of cell dysplasia associated with the transgene expression in hepatocytes largely located around the central veins by in situ hybridization analysis. In conclusion, the mutant HCV core protein at S99Q may contribute to the progress of HCV induced liver disease.
Amino Acid Sequence ; Animals ; Base Sequence ; Gene Expression ; Genetic Vectors/genetics ; Hepatitis C/*pathology/virology ; Hepatitis, Viral, Animal/*pathology/virology ; Hepatocytes/pathology/virology ; Liver/pathology/*virology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation/genetics ; RNA, Messenger/chemistry/metabolism ; Research Support, Non-U.S. Gov't ; Transgenes ; Viral Core Proteins/analysis/*genetics/metabolism

OBJECTIVETo evaluate the causes of alanine aminotransferase (ALT) level elevation in HBsAg-positive chronic hepatitis B (CHB) patients with low HBV DNA loads.

METHODSOne hundred nineteen HBsAg positive CHB patients with both serum HBV DNA loads less than 1000 copies/ml and ALT more than 1.25 upper limits of normal (ULN) lasting for at least 6 months were enrolled in this study. Patients co-infected with hepatitis C virus or HIV or suffering from other liver diseases were not included. HBV DNA loads were assayed by PCR. Serological biochemistry and liver biopsy histopathological changes and clinical characteristics of the patients were analyzed.

RESULTSOf the 119 patients 102 were males and 17 were females. The mean age of the patients was (33.9+/-9.7) years and their body mass index (BMI) was (23.4+/-3.7) kg/m2. Mean ALT levels were (150.0+/-166.6) U/L and AST levels were (102.4+/-193.2) U/L. Liver biopsies showed hepatic steatosis in 26.9 % (32/119) of the cases, chronic hepatitis in 53.8% (64/119), non-specific changes in 12.6% (15/119), and 1 without any change. However, hepatic steatosis was more frequently seen in patients taking nucleoside analogs (56.7%), x2=10.394, Probability value less than 0.01. BMI, apolipoprotein B (APO-B), triglyceride, cholesterol and uric acid were all significantly higher in patients with hepatic steatosis than those without (t values were 5.369, 4.276, 3.216, 4.223 and 2.438 respectively, all P less than 0.05) while ALT, AST and apolipoprotein A were much lower in those with steatosis than those without (t values were -2.234, -3.877 and -2.956 respectively, all P less than 0.05). Obesity, dyslipidemia and hyperuricemia were more frequently seen in patients with steatosis than in patients without it (x2 value 3.829, 7.659, 13.389, 0.549, all P less than 0.05). The severity of inflammation and fibrosis were also more significant in patients with steatosis (x2 value 20.978, 17.550, all P less than 0.05). As compared to those patients without specific changes, serum levels of ALT, AST, GGT in patients with chronic hepatitis were obviously higher, all P less than 0.05. In contrast, there were no significant differences in mean age, BMI, male preference, obesity, diabetes, dyslipidemia or hyperuricemia, and the levels of triglyceride, cholesterol, and fasting plasma glucose between the two groups.

CONCLUSIONOur data indicate that hepatic steatosis might be a factor associated with elevated ALT levels in HBsAg-positive CHB patients with low HBV DNA loads, especially in patients treated with nucleoside analogs.

Adult ; Alanine Transaminase ; blood ; Carrier State ; Fatty Liver ; physiopathology ; virology ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; virology ; Hepatocytes ; pathology ; Humans ; Male ; Viral Load ; Young Adult