1.P53 expression in liver tissue of patients with chronic hepatitis B and its influencing factors.
Jian-Chun GUO ; Xiang-Hua MA ; Yun-Hao XUN ; Li-Na XIAO ; Wei-Zhen SHI ; Jun-Ping SHI ; Wei-Wei WANG ; Guo-Qiang LOU
Chinese Journal of Experimental and Clinical Virology 2011;25(5):322-324
<b>OBJECTIVEb>To observe p53 expression in liver tissue of patients with chronic hepatitis B and its influencing factors.
<b>METHODSb>17 cases HBeAg-negative chronic hepatitis B patients and 31 cases HBeAg-positive chronic hepatitis B patients were divided into 2 groups.
<b>RESULTSb>(1) HBeAg-negative chronic hepatitis B patients were older, mostly male and HBV DNA lower. These three indicators between two groups patients appeared statistical difference. Serum markers were no statistical difference between two groups patients except Glo. (2) Pathological inflammation and fibrosis Staging were no statistical difference between two groups patients. p53 expression positive rate and p53 expression semi-quantitative scoring in liver tissue were no statistical difference between the two groups. (3) Logistic regression analysis showed that only liver fibrosis staging (S) is a risk factor for p53 expression. Compared with the S0-1, p53 expression increased by 3.9 times the rate of positive in S > or = 2.
<b>CONCLUSIONb>Liver fibrosis staging in patients with chronic hepatitis B is a risk factor for p53 positive expression in liver.
Adult ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; genetics ; metabolism ; pathology ; Humans ; Liver ; metabolism ; pathology ; Male ; Middle Aged ; Tumor Suppressor Protein p53 ; genetics ; metabolism
2.Increased expression of inducible nitric oxide synthase in chronic hepatitis B patients is correlated with histopathological grading and staging.
Juan WU ; Kai WANG ; Li-yan HAN ; Yu-chen FAN
Chinese Journal of Experimental and Clinical Virology 2008;22(1):57-59
<b>OBJECTIVEb>To investigate the intrahepatic expression of inducible nitric oxide synthase (iNOS) in patients with chronic hepatitis B (CHB) and its relation to liver histopathology.
<b>METHODSb>The intensity and distribution of the immunohistochemical staining of intrahepatic iNOS were studied in the liver biopsy specimens obtained from 74 patients with CHB and statistical analyses were performed between intrahepatic iNOS and ALT, HbeAg, HBV DNA grading of liver inflammation and staging of fibrosis. Seven histologically normal liver sections were used as a control group.
<b>RESULTSb>Compared with the control group, the intrahepatic iNOS immunoexpression was significantly higher in patients with CHB (P < 0.05), iNOS immunoreactivity was observed mainly in hepatocytes showing a predominant cytoplasmic staining, with the positive liver cells distributed diffusely throughout the hepatic lobule. Immunopositive staining could also be detected in Kupffer cells, sinusoidal lining cells and vascular endothelial cells. Compared with patients with normal ALT, the hepatocellular iNOS immunoexpression was significantly higher in patients with elevated ALT (P < 0.05) and the iNOS immunoexpression was significantly correlated with the serum level of ALT (r=0.601, P=0.000). Statistical analysis also showed that the intrahepatic iNOS immunoexpression was positively correlated with the grading of liver inflammation and the staging of liver fibrosis (r=0.660, P=0.000; r=0.507, P=0.000). No significant correlation between iNOS and HBeAg and HBV DNA was detected. CONCLUSION The intrahepatic expression of iNOS is elevated in chronic hepatitis B patients and correlated well with the severity of the disease, which indicated that inducible nitric oxide synthase may have a critical role in the pathogenesis of chronic viral hepatitis B.
Adult ; Alanine Transaminase ; metabolism ; DNA, Viral ; metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Hepatitis B Antigens ; metabolism ; Hepatitis B virus ; metabolism ; Hepatitis B, Chronic ; enzymology ; metabolism ; pathology ; virology ; Hepatocytes ; metabolism ; Humans ; Male ; Nitric Oxide Synthase Type II ; metabolism
3.The Degrees of Hepatocyte Cytoplasmic Expression of Hepatitis B Core Antigen correlate with Histologic Activity of Liver Disease in the Young Patients with Chronic Hepatitis B Infection.
Tae Hyeon KIM ; Eun Young CHO ; Hyo Jeong OH ; Chang Soo CHOI ; Ji Woong KIM ; Heung Bae MOON ; Haak Cheul KIM
Journal of Korean Medical Science 2006;21(2):279-283
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
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Liver/pathology/virology
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Humans
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Hepatocytes/pathology/*virology
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Hepatitis B, Chronic/*pathology/*virology
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Hepatitis B e Antigens/metabolism
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Hepatitis B Core Antigens/*metabolism
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DNA, Viral/blood
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Cytoplasm/virology
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Cell Nucleus/virology
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Adult
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Adolescent
4.Gene expression profile of peripheral blood monocyte in patients with fulminant hepatitis B by cDNA microarray.
Ying-xia LIU ; Guo-ling HU ; De-ming TAN ; Shu-ya HE ; Shuang-hu LIU
Chinese Journal of Hepatology 2003;11(3):153-155
<b>OBJECTIVEb>To investigate peripheral blood monocyte (PBMC) gene expression profile in patients with fulminant hepatic failure (FHF) by cDNA microarray.
<b>METHODSb>Microarrays consisting of 8,192 human cDNAs and labelled cDNAs prepared from PBMC in both 10 FHF patients and 10 asymtomatic surface antigen carriers (ASC) were applied to analyze gene expression. Relative ratios of gene expression in individuals were obtained by comparing the hybridization results, by GenePix 4000B scanning and by ImaGene3.0 software analysis, of Cy5-labelled cDNA from FHF patients with those of Cy3-labelled cDNA from ASC.
<b>RESULTSb>249 genes out of 8,192 were identified differently, at least two times. Most of the genes (79%) involved in cell signaling transduction, cell cycles, metabolism, inflammatory response and apoptosis, whose mRNAs were differently regulated.
<b>CONCLUSIONSb>These results suggest that HBV infection alters a broad range of cellular genes expression during developing into FHF and provide a framework for future functional study on the genes expressed differently.
DNA, Complementary ; genetics ; Female ; Gene Expression ; Gene Expression Profiling ; Hepatitis B ; genetics ; pathology ; Hepatitis B, Chronic ; genetics ; pathology ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Oligonucleotide Array Sequence Analysis
5.Level of serum and liver tissue TGF-beta1 in patients with liver fibrosis due to chronic hepatitis B.
Jian-chun GUO ; Jian-feng BAO ; Qun-wei CHEN ; Xiao-ou LI ; Jun-ping SHI ; Guo-qiang LOU ; Wei-zhen SHI ; Yun-hao XUN
Chinese Journal of Experimental and Clinical Virology 2008;22(5):354-357
<b>OBJECTIVEb>To detect the level of serum and liver tissue TGF-beta1 in patients with chronic hepatitis B, to study their relation to liver fibrosis and gain the evidence for diagnosis of liver fibrosis.
<b>METHODSb>The liver fibrosis grades (S0-S4) of 131 cases with chronic HBV infection were diagnosed after liver biopsy. Serum TGF-beta1 was detected by enzyme-linked immunosorbent assay, and the semiquantitative analysis was applied after detecting the expression of TGF-beta1 in liver tissue with immunohistochemistry. Their relations to liver fibrosis were analyzed.
<b>RESULTSb>Serum and tissue level of TGF-beta1 increased significantly with the development of fibrosis, and the same result was obtained between themselves (P < 0.01). There was very significant difference for serum level of TGF-beta1 among the groups with different fibrosis grades (P < 0.01). Serum levels of TGF-beta1 were decreased significantly comparing the Group S0 or S1 to S4 (P < 0.005). There were significant difference for serum level of TGF-beta1 among S0 and the others (P < 0.005). And there was significant difference between S1 and S3 (P < 0.005). The expression level of TGF-beta1 in liver tissue has no significant difference between group S3 and S4 (P > 0.05). However, the differences were significantly among the other comparisons (P < 0.01).
<b>CONCLUSIONb>There is close relation between the level of TGF-beta1 and the different liver fibrosis grades due to chronic hepatitis B. The serum level of TGF-beta1 is a potential noninvasive maker for diagnosis of liver fibrosis.
Adult ; Female ; Hepatitis B ; complications ; drug therapy ; metabolism ; pathology ; Hepatitis B virus ; genetics ; metabolism ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; Male ; Transforming Growth Factor beta1 ; blood ; metabolism
6.Increased expression of microfibrillar-associated protein 4 in chronic hepatitis B patients.
Sen-lin LI ; Yu-ning CAO ; Jing-run ZHAO ; Min WANG ; Zhong WANG
Chinese Journal of Hepatology 2012;20(6):474-475
Adult
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Carrier Proteins
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metabolism
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Extracellular Matrix Proteins
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metabolism
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Female
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Glycoproteins
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metabolism
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Hepatitis B, Chronic
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metabolism
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pathology
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Humans
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Liver
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metabolism
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pathology
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Male
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Middle Aged
8.Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance.
He-Bin FAN ; Ya-Bing GUO ; Bao-Ju WANG ; You-Fu ZHU ; Ai-Hua WU ; Jin-Lin HOU ; Dong-Liang YANG
Journal of Southern Medical University 2008;28(6):979-981
<b>OBJECTIVEb>To explore the role of interferon (IFN)-alpha/beta receptor beta subunit (IFNAR2) in the patients' response to IFN-alpha therapy as influenced by the grade of chronic hepatic inflammation, and understand the relation of IFNAR2 expression in the peripheral blood mononuclear cells (PBMCs) with HBV infection.
<b>METHODSb>Liver tissue specimens were obtained from 21 patients with chronic hepatitis B for examination of the hepatic inflammation, and PBMCs were isolated from another 16 patients with chronic hepatitis B and 15 health control subjects. Both the hepatic tissues and PBMCs were examined for IFNAR2 expression using immunohistochemistry.
<b>RESULTSb>The 21 patients with chronic hepatitis B were divided into 3 groups according to the severity of hepatic inflammation, namely G(1) (n=3), G(2) (n=7) and G(3) (n=11) groups. The patients in G(3) group showed had significantly higher IFNAR2 expressions in liver (25.1307-/+7.0700) than those of the G(1) (5.6913-/+1.8422) and G(2) (7.4706-/+5.3572) groups (P=0.000). The IFNAR2 levels in the PBMCs, however, did not show significant difference between patients with chronic hepatitis B and the healthy control subjects.
<b>CONCLUSIONb>In patients with chronic hepatitis B, IFNAR2 expression level is positively correlated to the severity of hepatic inflammation, and increased IFNAR2 expression in severe hepatic inflammation is therefore likely to result in increased response rate to INF-alpha therapy. The expression of IFNAR2 in the PBMCs is not associated with HBV infection.
Female ; Hepatitis B, Chronic ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Leukocytes, Mononuclear ; metabolism ; Liver ; metabolism ; pathology ; Male ; Receptor, Interferon alpha-beta ; blood ; metabolism
9.Association of liver histopathology and clinical features among patients with chronic hepatitis B virus infection.
Chinese Journal of Experimental and Clinical Virology 2011;25(3):214-216
<b>OBJECTIVEb>To explore the histopathological features of chronic hepatitis B virus (HBV) carriers and chronic hepatitis B (CHB) patients with mildly elevated serum alanine aminotransferase (ALT).
<b>METHODSb>105 patients were divided into three groups according to serum ALT levels: Group A [ALT level < or = 0.5 x upper limits of normal (ULN)], Group B (0.5 x ULN < ALT level < or = 1 x ULN) and Group C(1 x ULN < ALT level < 2 x ULN). Grade of liver inflammation and stage of liver fibrosis in the three groups were compared. The changes in clinical parameters were then observed in patients who had liver histopathological changes.
<b>RESULTSb>Among 40.95% of the patients, hepatitis degree went to G2 or even worse; and among 30.43% of the patients whose ALT level were normal, the hepatitis degree reached G2 or even worse. In 26.67% of the patients, degree of fibrosis went to S2 or even worse, and for the 17.39% patients whose ALT level were normal, degree of fibrosis went to S2 or even worse. The aggravation of liver inflammation and fibrosis was correlated with ALT and hyaluronic acid increasing (all P < 0.05).
<b>CONCLUSIONSb>Frequent monitoring of serum ALT and hyaluronic acid may help to understand histopathological changes in the liver. Liver biopsy applied to CHB should be regarded as a main basis if antiviral therapy should be conducted.
Adolescent ; Adult ; Alanine Transaminase ; metabolism ; Female ; Hepatitis B, Chronic ; metabolism ; pathology ; virology ; Humans ; Hyaluronic Acid ; metabolism ; Liver ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Young Adult
10.Construction and characterization of a cDNA library from human liver tissue with chronic hepatitis B.
Xiao-hong CHEN ; Zhi CHEN ; Hang-ping YAO ; Feng CHEN ; Hai-hong ZHU ; Hong-juan ZHOU
Journal of Zhejiang University. Science. B 2005;6(4):288-294
<b>OBJECTIVEb>To construct a cDNA library from human liver tissue with chronic hepatitis B and check its quality for investigating the expression level of liver tissue infected by hepatitis B virus. This will then be used to find the relevant genes and interesting proteins associated with the development of hepatitis B.
<b>METHODSb>The total RNA from liver tissue with chronic hepatitis B was extracted and the mRNA was purified using TRIZOL method. Switching mechanism at 5' end of the RNA transcript (SMART) technique and CDS III/3' primer were used for first-strand cDNA synthesis. Long distance polymerase chain reaction (LD PCR) was then used to synthesize the double-strand cDNA that was then digested by Sfi I and fractionated by CHROMA SPIN-400 column. The longer than 0.4 kb cDNAs were collected and ligated to lambdaTriplEx2 vector. Then lambda phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries were strictly checked by conventional titer determination. Fourteen plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector.
<b>RESULTSb>The titers of unamplifed and amplified libraries were 1.94 x 10(6) pfu/ml and 1.49 x 10(9) pfu/ml respectively. The percentages of recombinants from both libraries were 98.15% in unamplified library and 98.76% in amplified library. The lengths of the inserts were 1.23 kb in average, 1-2 kb in 64.29%, and 0.5-1.0 kb in 35.71%.
<b>CONCLUSIONb>A high quality cDNA library from human liver tissue with chronic hepatitis B was successfully constructed.
DNA, Complementary ; genetics ; Gene Library ; Hepatitis B, Chronic ; genetics ; Humans ; Liver ; metabolism ; pathology ; Polymerase Chain Reaction ; RNA ; analysis ; genetics