Caspase 3 ; metabolism ; Child ; Female ; Glomerulonephritis, Membranous ; enzymology ; etiology ; pathology ; virology ; Hepatitis B ; complications ; pathology ; Hepatitis B virus ; Humans ; Male

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

Animals ; Carcinoma, Hepatocellular ; genetics ; virology ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Neoplasms ; genetics ; virology ; Neoplasm Recurrence, Local ; genetics ; Point Mutation ; Telomerase ; metabolism

<b>OBJECTIVEb>To investigate relationship between glucose metabolic disorders and expression of insulin receptor (IR) and tyrosine protein kinase (TPK) in posthepatitic cirrhosis hepatocyte and HBV DNA expression in pancreatic cells.

<b>METHODSb>To detect HBV DNA in paraffin-embedded pancreatic and hepatic tissues from 12 posthepatitic cirrhosis patients with positive serum HBV markers by using in situ hybridization (ISH) with a digoxigenin labelled probe. The amount of IR and TPK have been evaluated by immunohistochemical quantitative analysis using image analyzer in hepatocyte of 12 patients positive for HBV markers with posthepatitic cirrhosis in serum. Immunofluorescent histochemical double staining technique was used. HBsAg and IR were observed under confocal laser scanning microscope.

<b>RESULTSb>Eleven of 12 cirrhosis patients? hepatocytes were HBV DNA positive, including 7 patients (7/7) with impaired glucose tolerance (IGT) and 4 patients (4/5) with normal glucose tolerance (NGT). Eight of 12 pancreatic cells were HBV DNA positive, including 7 patients (7/7) with IGT, but only one patient (1/5) with NGT-HBV DNA was found positive in pancreatic cells in significantly more subjects in IGT group than in NGT group (P less than 0.01).IR and TPK amount in hepatocyte of IGT was significantly less than that of NGT patients with posthepatitic cirrhosis (P less than 0.01). IR amount was closely related to the TPK in cirrhosis hepatocyte r=0.82597(P less than 0.01). HBV DNA was mainly localized in the nuclei of hepatocyte and pancreatic acinar and islet cells. Immunofluorescent histochemical double-staining showed that HBsAg was partly localized in the IR positive areas of hepatocytes and pancreatic islet cells.

<b>CONCLUSIONb>HBV can invade acinar cells of pancreas and islet cells, which might be a direct cause of insulin-dependent diabetes mellitus-like the disorder and insulin absence after HBV infection. Decrease of IR and TPK might be main cause of noninsulin-dependent diabetes mellitus-like disorder after having hepatitis or posthepatitic cirrhosis.

DNA, Viral ; analysis ; Female ; Glucose Metabolism Disorders ; complications ; metabolism ; virology ; Hepatitis B virus ; genetics ; Hepatocytes ; metabolism ; virology ; Humans ; In Situ Hybridization ; Liver Cirrhosis ; complications ; metabolism ; virology ; Male ; Middle Aged ; Pancreas ; cytology ; virology ; Protein-Tyrosine Kinases ; metabolism ; Receptor, Insulin ; metabolism

<b>BACKGROUNDb>The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.

<b>METHODSb>According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO2, SaO2 and hypoxemia were analyzed.

<b>RESULTSb>The COHb level in group P-H ((1.672 ± 0.761)%) was significantly higher than that in group N ((0.983 ± 0.231)%) (P < 0.01), and the level in group H ((2.102 ± 1.021)%) was significantly higher than groups P-H and N (P < 0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r(s) = 0.357, P = 0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302 ± 1.072)% vs. (1.802 ± 1.041)%, P > 0.05) or the occurrence of SBP ((2.960 ± 0.561)% vs. (2.030 ± 1.021)%, P > 0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502 ± 1.073)% vs. (1.981 ± 1.020)%, P = 0.029). The COHb level had a negative correlation with PaO2 (r = -0.335, P = 0.007) while no statistically significant relationship was found with SaO2 (r = -0.071, P > 0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621 ± 0.880)% vs. (1.910 ± 0.931)%, P = 0.011).

<b>CONCLUSIONSb>COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.

Adult ; Aged ; Carboxyhemoglobin ; metabolism ; Female ; Fibrosis ; complications ; virology ; Hepatic Encephalopathy ; metabolism ; Hepatitis B virus ; pathogenicity ; Humans ; Male ; Middle Aged

<b>OBJECTIVEb>To investigate the expression of HBx and COX-2 in hepatitis B virus-related hepatocellular carcinoma, and Its correlation with microangiogenesis and metastasis, and possible mechanism.

<b>METHODSb>Immunohistochemistry was used to detect the expression of hepatitis B virus X, cyclooxygenase-2 and CD34 in hepatitis B virus related hepatic carcinoma and 22 non-HBV related hepatic carcinoma tissues. The expression of hepatitis B virus x protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma correlated with microangiogenesis and metastasis was tested by Spearman correlation analysis. The expression of COX-2 in HepG2-X was detected by Western blot and RT-PCR. PGE2 was detected by ELISA in clear supernatant liquid of HepG2-X. Trypan blue exclusion was performed to examine the inhibitory effects of COX-2 selective inhibitor (celecoxib).

<b>RESULTSb>In Hepatitis B carcinoma tissue, HBx and COX-2 were expressed at high level. The positive rate of COX-2 expression was 88.87% (55/62) in HBx positive expression group, which was significantly higher than that of the positive expression 31.82% (7/22, x2=27.188, P<0.01) in HBx negative expression group and 40.91% (9/22, x2=20.453, P<0.01) in non-HBV related hepatic carcinoma tissues, but it had no statistical difference (x2=0.393, P=0.531) between the HBx negative expression group and non-HBV related hepatic carcinoma tissue group. The expressions of HBx and COX-2 in metastasis group were higher than that in non-metastasis group (P<0.01), MVD in HBx or COX-2 positive expression group was significantly higher than that in negative expression group and non-HBV related hepatic carcinoma tissues (P is less than 0.01). MVD with metastasis was higher than that without metastasis (P<0.01) and MVD with portal vein invasion was higher than that without invasion (P<0.05). Spearman correlation analysis showed that the expression of COX-2 was significantly correlated with the expression of HBx (Rs=0.568, P<0.01). Celecoxib suppressed the growth of both cells in a dose-dependent manner. HepG2-X was significantly susceptible to celecoxib as compared to the HepG2-PC cells. COX-2 protein and mRNA were upregulated in HepG2-X cells than in HepG2-PC. Moreover, PGE2 was upregulated in clear supernatant liquid of HepG2-X than in HepG2-PC.

<b>CONCLUSIONb>The expressions of HBx and COX-2 were higher in HBV-related hepatocellular carcinoma. COX-2 was significantly correlated with HBx in HCC and it could be a key factor involved in HBx contributed hepatocellular carcinoma's microangiogenesis and metastasis. The possible mechanism of the dual effects might be through HBx, COX-2 and PGE2 pathways in infiltration involved metastasis and microangiogenesis involved metastasis.

Carcinoma, Hepatocellular ; blood supply ; etiology ; metabolism ; virology ; Cell Line, Tumor ; Cyclooxygenase 2 ; metabolism ; Hepatitis B ; complications ; Hepatitis B virus ; metabolism ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; virology ; Neoplasm Metastasis ; Neovascularization, Pathologic ; Trans-Activators ; metabolism

<b>OBJECTIVEb>Investigated the impact of HBV infection on sperm DNA integrity and its applied significance.

<b>METHODSb>12 cases infertility male with HBV infection in patient group and 11 cases of normal male without HBV infection in the control group were by SCD and CASA.

<b>RESULTSb>The DFI in the patient group was (23.4 +/- 10.2)%, while it was in the control group was (11.6 +/- 5.9)%. The difference of the DFI in these two groups was significantly, P < 0.01. The sperm concentration and forward motility (a + b) in the patient group were lower than that in the control group, P < 0.01. There were also significantly of the normal sperm and sperm activity between the two groups.

<b>CONCLUSIONb>HBV infection not only affected the conventional semen parameters, but also caused serious damage on sperm DNA.

Adult ; Case-Control Studies ; DNA Damage ; Hepatitis B ; complications ; Hepatitis B virus ; physiology ; Humans ; Infertility, Male ; etiology ; genetics ; virology ; Male ; Sperm Count ; Sperm Motility ; Spermatozoa ; cytology ; metabolism

<b>OBJECTIVEb>To study the correlation between HBsAg and HCV in hepatocellular carcinoma (HCC) pericarcinomatous tissues and serum liver fibrosis markers.

<b>METHODSb>The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied with paraffin sections using immunohistochemistry techniques. Hyaluronic acid (HA), procollagen III peptide (PIIIP), collagen IV (CIV), and laminin (LN) were detected by radioimmunoassay.

<b>RESULTSb>The levels of HA, PIIIP, CIV and LN in the HBV and HCV coinfection group were the highest among the four groups. The levels of HA, PIIIP, CIV and LN in the groups not infected by HBV and HCV were the lowest among the four groups. HBV and HCV expressions were positively correlated with HA, LN and CIV and their Spearman's rank correlation coefficients were 0.60, 0.45, 0.46, respectively (P < 0.01).

<b>CONCLUSIONb>Liver cancer development follows a sequential trend of chronic hepatitis, liver cirrhosis, and liver cancer. In the tissues of liver cancer with virus infection background, the serum marker level of hepatic fibrosis is obviously higher than those without virus infection background. On the one hand, virus infection is one of the reasons causing liver cancer; and on the other hand, longstanding viremia will aggravate pathological changes of liver tissues. Therefore antivirus treatment of hepatitis is of significance for the prognosis of liver cancer.

Adult ; Aged ; Carcinoma, Hepatocellular ; complications ; virology ; Collagen Type IV ; metabolism ; Female ; Hepacivirus ; immunology ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B virus ; immunology ; Hepatitis C Antigens ; metabolism ; Humans ; Hyaluronic Acid ; metabolism ; Laminin ; metabolism ; Liver Cirrhosis ; complications ; virology ; Liver Neoplasms ; complications ; virology ; Male ; Middle Aged ; Procollagen ; metabolism

A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99mTc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and biochemical abnormalities do not respond to a low-fat diet.
Adolescent ; Adult ; Duodenum/pathology ; Female ; Hepatitis B/complications ; Hepatitis B Virus/metabolism ; Human ; Intestinal Diseases/*drug therapy/virology ; Jejunum/pathology ; Liver Cirrhosis/*drug therapy/virology ; Lymphangiectasis, Intestinal/*drug therapy/virology ; Male ; Middle Aged ; Octreotide/*pharmacology ; Protein-Losing Enteropathies/*drug therapy

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis.
Apoptosis/genetics ; Carcinoma, Hepatocellular/pathology/*virology ; Cell Cycle ; DNA Mismatch Repair ; Hepatitis B virus/genetics/*pathogenicity ; Hepatitis B, Chronic/*complications ; Humans ; Liver Neoplasms/pathology/*virology ; Neovascularization, Pathologic/genetics/virology ; Telomere/genetics ; Trans-Activators/*metabolism ; Transcription, Genetic