Background: Hepatitis B is an infectious illness caused by hepatitis B virus (HBV) which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Objectives: The aim of study is to clarify clinical features and molecular characteristics of HBV in chronic HBV-infected patients with A 1899 mutation. Subjects and method: HBV genotype, HBV-ONA level, HBeAg and anti-HBe in 29 chronic HBV-infected patients were determined by PCR-RFLP, Real-time PCR and ELISA, respectively. Mutations were analyzed by direct sequencing. Results: Mutations in core-promoter/precore regions of HBV genome can suppress HBeAg secretion and stimulate HBV-ONA replication. The prevalence of hepatocel- lular carcinoma (HCc): 10/29, liver cirrhosis (LC) : 15/29 are significantly higher than that in chronic hepatitis (CH) : 4/29 (P < 0.001). HbeAg seroconversion rate in CH (75%) is higher than that in HCC \r\n', u'(40%) and in LC (53.3%), but not significant (P > 0.05). ALT level is the highest in CH and the lowest in HCC \r\n', u'(P = 0.02), 8/10 (80%) HCC patients have normal range of ALT. HBV-ONA level in HCC and in LC is significantly higher than that in CH (P = 0.024). The emerging of A 1899 is often accompanied by C/G1753 mutation (37.9%) and dual core-promoter mutation T1762A1764 (79.3%). Conclusion: A1899 mutation can play a role in the pathogenesis of liver diseases in chronic HBV-infected Vietnamese.\r\n', u'
Hepatitis B virus/ growth & ; development ; physiology ; Hepatitis B ; Chronic/ pathology ; transmission

<b>OBJECTIVEb>To investigate the expression of human annexin-V (HA-V) in relation to HBV infection in different fetal tissues.

<b>METHODSb>Immunohistochemistry was employed to detect the expression and distribution of HA-V in the liver, kidney, ovary, heart, fallopian tube, spleen, and thymus gland of human fetus.

<b>RESULTSb>HA-V expression was detected in different tissues including the ovary, liver, intrahepatic bile duct, heart, kidney, lymphocytic cells in the thymus gland, epithelial cells of the fallopian, and cortical and medullary cells of the spleen. HA-V was distributed mainly in the cytoplasm of the cells. The liver tissues exhibited greater gray scale for HA-V expression than in the other tissues (P<0.05) and no significant difference was observed in the other tissues than the liver (P>0.05) in image analysis with Photoshop 7.0.

<b>CONCLUSIONb>HA-V is an inherent protein in fetal tissues with possible relation to HBV infection of different tissues as a HBV receptor. Greater amount of HA-V in the liver may account for the vulnerability of the liver to HBV infection.

Annexin A5 ; analysis ; Fetus ; chemistry ; virology ; Hepatitis B ; metabolism ; virology ; Hepatitis B virus ; growth & development ; Humans ; Immunohistochemistry ; Liver ; chemistry ; virology ; Tissue Distribution

Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Female ; Hepatitis B virus ; growth & development ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Male ; Middle Aged ; Viral Load

<b>OBJECTIVEb>To investigate the short-term spontaneous fluctuation of viral load in patients with chronic hepatitis B (CHB) and explore the related factors in treatment naive CHB patients during immune clearance phase.

<b>METHODSb>A total of 123 treatment naive HBeAg-positive CHB patients with ALT>2 × ULN were enrolled in this study. Paired serum samples were obtained at the first and second visits with an interval of less than 4 weeks. The levels of quantitative HBV DNA (Roche COBAS), quantitative HBsAg, ALT and AST were analyzed. Liver biopsy specimen were collected within 4 weeks and evaluated using Knodell and Ishak histological scoring system.

<b>RESULTSb>Of the 123 patients, 93 (75.6%) and 30 (24.4%) had HBV DNA fluctuation ≤ 0.5 Log IU/ml and >0.5 Log IU/ml, respectively. Binary logistic multivariate regression analysis identified Knodell necroinflammation score and HBV DNA level as the factors related to HBV DNA fluctuation. Patients with Knodell necorinflammation score ≥ 10 or HBV DNA<7 Log IU/ml had significantly higher rates of HBV DNA fluctuation>0.5 Log IU/ml (50.0% vs 18.3%, P=0.042; 42.9% vs 20.6%, P=0.030).

<b>CONCLUSIONb>Treatment naive CHB patients in immune clearance phase show short-term spontaneous fluctuation of HBV DNA, and nearly 25% of the patients have HBV DNA fluctuation >0.5 Log IU/ml. Such fluctuation is related to liver inflammation and quantity of HBV DNA.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; growth & development ; Hepatitis B, Chronic ; virology ; Humans ; Liver ; physiopathology ; Male ; Viral Load ; statistics & numerical data ; Young Adult

BACKGROUND: The seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity.PURPOSE: To investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy.METHODS: We recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents.RESULTS: Our subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P<0.001). The anti-HBs titer was significantly decreased as the BMI z score increased adjusting for age and sex (B=-15.725; standard error=5.494; P=0.004). The probability of anti-HBs seropositivity based on BMI z score was decreased to an OR of 0.820 after the control for confounding variables (95% confidence interval, 0.728–0.923; P=0.001).CONCLUSION: There was a significant association between anti-HBs titer and BMI z score after adjustment for age and sex. Our results indicate that BMI is a potential factor affecting anti-HBs titer in healthy children.
Adolescent ; Adult ; Antibodies ; Body Mass Index ; Body Weight ; Child ; Confounding Factors (Epidemiology) ; Female ; Growth Charts ; Healthy Volunteers ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoassay ; Male ; Methods ; Obesity ; Vaccination

BACKGROUND/AIMS: Transforming growth factor-a(TGF-a) is a polypeptide cytokine related to cell proliferation and transformation. TGF-a binds to EGF receptor and stimulating DNA synthesis in liver cell. The hepatitis B virus (HBV) by itself is also believed to play a role in the hepatic carcinogenesis. Recently, it was reported that TGF-a and HBV were synergistic in action with rapid appearance of hepatocelluar carcinoma in bitransgenic mice. Although TGF- a is thought to play an important role in hepatocarcinogenesis, its expression during the natural history of HBV hepatitis was poorly understood. This investigation was performed to elucidate the dynamic changes and istinct immunohistochemical staining patterns in the course of chronic HBV hepatitis with specific reference to hepatocelluar carcinoma and to explain the role of TGF-a in the pathogenesis of hepatocelluar carcinoma. MATERIALS/METHODS: Employing TGF-a monoclonal antibody, signal detection was carried out by peroxidase-conjugated streptavidin in deparaffinized liver tissue sections taken from HBsAg positive patients. All of the liver tissue sections were proven HBV DNA positive by in situ hybridization. Immunohistochemical staining was performed in the tissue sections obtained from four normal controls, six from patients with chronic persistent hepatitis, five with chronic active hepatitis, eight with liver cirrhosis and eleven with hepatocellular carcinoma. RESULTS: The patterns of TGF-a immunoreactivity were cytoplasmic-grain types in normal controls and chronic persistent hepatitis, honeycomb types in chronic active hepatitis, occasional cytoplasmic-flooding types in liver cirrhosis, and cytoplasmic-grape types in hepatocellular carcinoma. A Shapiro-Wilk W test for frequency table analysis for the expression of TGF-a in these different disease groups was statistically significant. CONCLUSION: These data suggest that step-wise distinct expression of TGF-a enhancement in HBV associated chranic liver diseases which eventually resulted in the development of hepatocellular carcinoma were conceivably due to dysregulation of liver cell cycles by both HBV and TGF-a during the persistent repetition of cell cycles.
Animals ; Carcinogenesis ; Carcinoma, Hepatocellular* ; Cell Cycle ; Cell Proliferation ; DNA ; Hepatitis ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis, Chronic* ; Humans ; In Situ Hybridization ; Liver Cirrhosis* ; Liver Diseases ; Liver* ; Mice ; Natural History ; Receptor, Epidermal Growth Factor ; Streptavidin

<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

<b>OBJECTIVEb>To establish a culture system of HBV positive serum infected Hep G2 cells in vitro.

<b>METHODSb>Hep G2 cells were seeded into six-well cluster dishes, at 1 x 10(-6) cells per well and incubated with 3 ml 10% fetal calf serum/ Dulbecco's modified Eagle's medium (10% FCS/DMEM) at 37 degrees in 5% CO2 air. At 24 h after plating, infection group Hep G2 cells were cultured with 0.5 ml HBV positive serum, in control group HBV negative serum was used, 24 h later the inoculums was removed. The cells were then extensively washed with 0.01 mol/L phosphate-buffered saline (PBS). After washing with PBS, 4 ml 2% FCS/DMEM were added to each well and the medium was collected every 12 h. ELISA method was used to detect HBsAg in culture medium. HBV DNA in cells and culture medium was detected by PCR.

<b>RESULTSb>In infection group, HBsAg could be detected from cell culture medium from 12 h (after PBS washed) to 84 h. HBV DNA could be detected by PCR in culture medium and cells.

<b>CONCLUSIONb>Infection of Hep G2 cells by HBV positive serum is feasible.

Carcinoma, Hepatocellular ; pathology ; virology ; Cell Line, Tumor ; DNA, Viral ; genetics ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; blood ; virology ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B virus ; genetics ; growth & development ; immunology ; Humans ; Liver Neoplasms ; pathology ; virology ; Polymerase Chain Reaction ; Serum ; virology

BACKGROUNDS/AIMS: Hepatitis B virus (HBV) replicates via RNA intermediates, which could serve as targets for RNA interference (RNAi). Vector-mediated short-hairpin RNA (shRNA) can induce sustained RNAi in comparison to small interfering RNA. Lentiviral vector is known to induce prolonged RNAi with high transduction efficiency. In this study, we sought to test the in vitro efficacy of shRNA delivered by a lentiviral vector in suppressing the replication of HBV. METHODS: Two shRNA sequences against the hepatitis B viral protein HBx (sh1580 and sh1685) were cloned downstream of the U6 promoter in an HIV-based plasmid to generate third-generation lentiviral vectors. HepAD38 cells were transduced with anti-HBx lentiviral vectors, and HBV replication was induced for 5 days. HBV DNA was isolated and quantified using real-time PCR. RESULTS: Lentiviral vectors encoding the shRNA against HBV transduced HepAD38 cells with high efficacy. The total intracellular HBV DNA content was significantly reduced by both sh1580 and sh1685 (2.9% and 12.0%, respectively; P<0.05). HBV covalently closed circular DNA (cccDNA) was also suppressed significantly (19.7% and 25.5%, respectively; P<0.05). CONCLUSIONS: Lentivirus-mediated delivery of shRNA against HBx can effectively suppress the replication of HBV and reduce HBV cccDNA in cell culture systems.
Cell Line, Tumor ; Genetic Vectors ; Hepatitis B virus/*genetics/growth & development/physiology ; Humans ; Lentivirus/*genetics ; *RNA Interference ; RNA, Viral/metabolism ; Trans-Activators/*antagonists & inhibitors/genetics/metabolism ; *Virus Replication

No abstract available.
Genetic Vectors ; Hepatitis B virus/*genetics/growth & development/physiology ; Humans ; Lentivirus/genetics ; *RNA Interference ; RNA, Viral/metabolism ; Trans-Activators/antagonists & inhibitors/genetics ; *Virus Replication