Adenovirus Infections, Human ; pathology ; virology ; Glomerulonephritis, Membranous ; pathology ; virology ; HIV Infections ; pathology ; virology ; Hepatitis B ; pathology ; virology ; Hepatitis C ; pathology ; virology ; Herpes Zoster ; pathology ; virology ; Herpesvirus 3, Human ; isolation & purification ; Humans ; Kidney ; pathology ; virology ; Kidney Diseases ; pathology ; virology ; Nephritis, Interstitial ; pathology ; virology ; Parvoviridae Infections ; pathology ; virology ; Parvovirus B19, Human ; isolation & purification

Angiomyolipoma ; pathology ; Bile Duct Neoplasms ; pathology ; virology ; Bile Ducts, Intrahepatic ; Carcinoma, Hepatocellular ; pathology ; virology ; Carcinosarcoma ; pathology ; Cholangiocarcinoma ; pathology ; virology ; Hepatitis B ; Hepatitis C ; Humans ; Liver Neoplasms ; pathology ; virology ; Pathology, Clinical ; trends

Adult ; Aged ; B-Lymphocytes ; pathology ; Female ; Gastric Mucosa ; pathology ; Hepatitis B, Chronic ; complications ; epidemiology ; virology ; Hepatitis C, Chronic ; complications ; epidemiology ; virology ; Humans ; Immunohistochemistry ; Liver ; pathology ; Lymphoma ; etiology ; pathology ; virology ; Male ; Middle Aged ; Staining and Labeling

OBJECTIVETo study the correlation between hepatitis B virus surface antigen (HBsAg) and hepatitis C virus (HCV) expression as well as fibrosis staging in hepatocellular carcinoma (HCC) and pericarcinomatous tissues.

METHODSThe patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embeded sections with immunohistochemistry technique, and liver tissues were also staged.

RESULTSHBV, HCV virus infection were positively correlated with the fibrotic staging (r(s) = 0.32, P = 0.001). HBsAg and HCV were detected both in HCC and pericarcinomatous tissues. The positive rate of HBsAg in Pericarcinomatous Tissues (79%) was higher than that of in HCC tissues (23%). HCV expressions in HCC (15%) and pericarcinomatous tissues (23%) showed no significant differences.

CONCLUSIONThe fibrotic degree in the tissues of liver cancer with previous virus infection was obviously higher than that without virus infection. Viral infection seemed to be one of the reasons causing liver cancer while perennial virusemia would aggravate pathological changes of the liver tissue.

Carcinoma, Hepatocellular ; pathology ; virology ; Hepacivirus ; isolation & purification ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; isolation & purification ; Hepatitis B virus ; isolation & purification ; Hepatitis C ; complications ; Hepatitis C Antigens ; genetics ; Humans ; Liver ; pathology ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; virology ; Precancerous Conditions ; pathology ; virology ; Risk Factors

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.
Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Hepatocellular/*etiology ; Hepacivirus/genetics/*pathogenicity ; Hepatitis C/complications/pathology/virology ; Humans ; Liver Neoplasms/*etiology ; Risk

OBJECTIVETo explore the role of hepatitis C virus core protein on the infiltration and metastasis of cholangiocarcinoma tissues.

METHODSFrom January 2001 to November 2006, 34 patients with cholangiocarcinoma who had intact follow-up data randomly were chosen. The expression of HCVc protein, epithelium markers and mesenchymal markers in cholangiocarcinoma tissues were examined by SP methods of immunohistochemistry, clinical-pathological data were recorded and analyzed.

RESULTSThe positive expression rate was observed in 47.1% for HCVc protein, 50% for N-cadherin, 44.1% for Vimentin, 55.9% for Fibronectin and the decreased expression rate was E-cadherin for 55.9%, alpha-catenin for 70.6%, beta-catenin for 55.9%. The positive expression of HCVc protein was associated with the decreased expression of E-cadherin, alpha-catenin and the positive expression of N-cadherin, Vimentin, Fibronectin (chi(2) = 4.480, 4.163, 4.250, 7.438, 12.260, P < 0.05). A positive-correlation between the expression of HCVc protein and metastasis of lymph nodes and other organs were found (chi(2) = 5.708, 4.163, P < 0.05).

CONCLUSIONHCVc protein might promote cholangiocarcinoma tissues' infiltration and metastasis by inducing it's epithelial-mesenchymal transition.

Adult ; Aged ; Cell Transformation, Neoplastic ; Cholangiocarcinoma ; metabolism ; pathology ; virology ; Epithelium ; metabolism ; pathology ; virology ; Female ; Hepacivirus ; metabolism ; Hepatitis C ; metabolism ; pathology ; virology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Viral Core Proteins ; metabolism ; physiology

OBJECTIVEEstablish the model of mouse with chronic hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD).

METHODSTake 100 HBV transgenic, BALB/c mice of 4 weeks old, with each gender half. Then pick out 70 mice in one group to feed high-fat feed and the rest to feed normal feed. At the end of week 16, random kill 10 mice of high-fat, then liver tissue and serological detection target identification model is established in this paper. After that, divide the mice into model group and comparison group with 30 mice in each group. Feed model group with high-fat feed, comparison group with normal feed and normal group with normal feed till week 72 (including previous 16 weeks). Kill 10 mice of each group at the end of week 24, 48 and 72 respectively, fully automatic biochemical instrument detection of serum ALT, AST, TC, TG, FBG, fluorescence quantitative PCR method to detect HBV-DNA, chemiluminescence detection of HBsAg, liver biopsy after HE staining to evaluate histology change, observe mice model of dynamic evolution.

RESULTS(1) Feed high fat feed after 16 weeks, mice's weight, serum ALT, AST, TC, TG, FBG and blood biochemical indicators increased, HBV-DNA positive, liver HE staining obviously big blister fatty degeneration of liver cells and within the lobule lymphocytes infiltration, NAFLD activity score (NAS) getting close to NASH, the model of chronic HBV carries with NAFLD mouse built successfully. (2) The TC and TG values of model group in each period were higher than that of comparison group and normal group. (3) In week 24 and 72, HBV-DNA values of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P < 0.05). (4) In week 48 and 72, NAS of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P < 0.05).

CONCLUSIONS(1) Chronic HBV carries with NAFLD mice model can be established by HBV transgenic mice fed by high fat feed. (2) NAFLD accelerates the liver disease of the mice carrying HBV to some extent.

Animals ; Disease Models, Animal ; Fatty Liver ; complications ; pathology ; virology ; Female ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis B, Chronic ; complications ; pathology ; virology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Non-alcoholic Fatty Liver Disease

BACKGROUNDTo test susceptibility of human liver cell line Hep G2 to HCV in vitro.

METHODSHep G2 was cultivated with the serum from a chronic hepatitis C patient. After inoculation, plus and minus strand of HCV RNA, the expression of HCV NS3 antigen and the location of HCV RNA in cell and/or supernatant were examined by RT-PCR, immunohistochemistry and in situ hybridization, respectively.

RESULTSHCV RNA could be detected from day 2 to day 40 post-inoculation in both cell and supernatant. HCV NS3 antigen could be expressed in infected cells and HCV RNA was mainly situated within cytoplasm.

CONCLUSIONSThe results suggested that HepG2 cell line was not only susceptible to HCV but also could support its replication in vitro.

Carcinoma, Hepatocellular ; pathology ; virology ; Coculture Techniques ; Hepacivirus ; genetics ; growth & development ; physiology ; Hepatitis C, Chronic ; virology ; Humans ; Liver Neoplasms ; pathology ; virology ; RNA, Viral ; analysis ; biosynthesis ; genetics ; Tumor Cells, Cultured ; Viral Nonstructural Proteins ; biosynthesis ; genetics ; Virus Replication

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 investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL).

METHODSHBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were examined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy).

RESULTSSubjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9+/-1.4) vs (4.1+/-1.1) log(10)copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HAI) > or = to 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAI) > or = to 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, x(2)=0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r=0.626, 0.592, P < 0.01; BCP: r=0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F > or = 3) (AUC = 0.905, 95% CI: 0.771-1.039, P < 0.05) with the cutoff value of 4.5 log(10) copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA is > or = to 10(4) copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 log(10)copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes.

CONCLUSIONSVirus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting significant fibrosis (F > or = 3).

Adult ; Alanine Transaminase ; blood ; Base Sequence ; Carrier State ; pathology ; virology ; DNA, Viral ; blood ; genetics ; Female ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis C, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Mutation ; Promoter Regions, Genetic ; genetics ; Viral Load