BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.
Cytoplasm ; Fibrosis ; Hepatitis B Core Antigens* ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B* ; Hepatitis B, Chronic* ; Hepatitis* ; Hepatitis, Chronic* ; Hepatocytes* ; Humans ; Viral Load ; Viremia

BACKGROUND/AIMS: The purpose of this study was to assess the correlation between histologic activity and fibrosis and the distribution of intrahepatic hepatitis B core antigen (HBcAg) and surface antigen (HBsAg) in patients with chronic hepatitis B. METHODS: 141 patients (M:F=141:27) with biopsy-proven chronic hepatitis B, abnormal liver function, and a positive HBV viral marker (serum HBeAg, serum HBV DNA) were enrolled. RESULTS: HBcAg was expressed in 96 of 141 patients (68.1%), nHBcAg in 23 (16.3%), cHBcAg in 58 (41.2%), and n-cHBcAg in 15 (10.6%). In the cases of HBsAg, 114 of 141 patients (80.9%) were expressed as cHBsAg, 2 (1.4%) as mHBsAg, and 16 (11.3%) as m-cHBsAg. The presence of intrahepatic HBcAg and HBsAg according to Gudat's classification was not correlated with activity and fibrosis. But the groups with nuclear expression of HBcAg revealed less inflammatory activity (grade, p=0.003), and less fibrotic stage (p = 0.002) than with cytoplasmic or no expression of HBcAg. HBsAg was not. CONCLUSIONS: These observations suggest that inflammatory activity and fibrosis of chronic hepatitis B are related to the presence of HBcAg in hepatocytes and the expression of HBcAg. This is a very important finding in hepatocytolysis.
Antigens, Surface ; Biomarkers ; Classification ; Cytoplasm ; Fibrosis* ; Hepatitis B Core Antigens* ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Hepatocytes ; Humans ; Immunohistochemistry ; Liver

BACKGROUND/AIMS: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg. METHODS: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively. RESULTS: The stage of fibrosis was higher (3.31+/-1.34 vs. 2.43+/-1.39, mean+/-SD, p<0.01) and the grade of necroinflammatory activity was higher (9.39+/-3.11 vs. 6.13+/-3.40, p<0.001) for the cytoplasmic expression of HBcAg (cHBcAg) than for the nuclear expression of HBcAg (nHBcAg). The serum HBV DNA level was 677.30+/-983.14 pg/mL in cHBcAg, 1274.46+/-1417.28 pg/mL in nHBcAg, 1121.01+/-1121.0 pg/mL in c-nHBcAg, and 229.47+/-678.92 pg/mL in negative (p<0.001). HBeAg was seropositive in 74.7% of patients with cHBcAg, 90.6% in those with nHBcAg, 90.3% in those with n-cHBcAg, and 55.6% in those with negative (p<0.001). The histologic stage and grade of hepatitis were not significantly correlated with the subcellular localization of intrahepatic HBsAg (p>0.05). CONCLUSIONS: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg.
Antigens, Surface ; Biopsy ; Cytoplasm ; DNA ; Fibrosis ; Hepatitis ; Hepatitis B Core Antigens ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Liver ; Liver Diseases ; Medical Records ; Retrospective Studies ; Virus Replication

Alanine Transaminase ; blood ; DNA, Viral ; blood ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; virology ; Humans

<b>OBJECTIVEb>To analyze the characteristic of T cell response to specific antigen proteins in patients with hepatitis B virus infection.

<b>METHODSb>76 cases were recruited, including four groups, acute hepatitis B (AHB), active phase of chronic hepatitis B (CHB), inactive HBV carriers (AsC) and past HBV infection. T cell responses stimulated by 3 antigen specific proteins of HBV were detected using enzyme linked immunospot (ELISPOT) assay.

<b>RESULTSb>(1) There were no significant difference in frequencies to HBsAg, HBcAg and HBeAg in AHB and CHB. The frequencies to HBsAg and HBcAg in AsC were lower than that to HBeAg, and the frequencies to HBsAg in group of past HBV infection were significantly lower than that to HBcAg and HBeAg. (2) The frequencies to HBsAg in AHB and CHB both were higher than in group of past HBV infection. The frequencies to HBcAg of AHB, CHB and AsC were higher than that of group of past HBV infection. (3) There were no significant difference in magnitude to HBsAg, HBcAg and HBeAg in AHB and AsC. In CHB, the magnitude to HBsAg was lower than that to HBcAg. The magnitude of in group of past HBV infection were HBcAg > HBeAg > HBsAg. (4) In four groups, the sequence of the magnitude to HBsAg from high to low was AHB, CHB, group of past HBV infection and AsC. The magnitude to HBcAg in of AsC was lower than other three groups. As to the magnitude to HBeAg, the difference was no significant between any two groups except between AHB and CHB.

<b>CONCLUSIONSb>The T cell responses in group of AsC to HBeAg were the highest, while the T cell responses to HBcAg were the highest in group of other groups.

Hepatitis B ; immunology ; virology ; Hepatitis B Antibodies ; immunology ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B e Antigens ; immunology ; Hepatitis B virus ; immunology ; isolation & purification ; Humans ; T-Lymphocytes ; immunology

PURPOSE: The lack of reliable in vitro infection systems or convenient animal models has hindered the progress of hepatitis B virus (HBV) research and the development of new treatment options. We established an in vitro model of hepatitis B, using recombinant HBV encoding baculovirus, which provided HBV replication and antigens expression in HepG2 cells. The objectives of this study were to characterize the magnitude of HBV expression and the level of replication obtainable in HepG2 cells, to establish the optimum infection and culture conditions of HBV expression and replication. METHODS: Replication of a competent HBV genome encoding the baculovirus, RC-HBV-Bac, was generated for delivering the HBV genome to HepG2 cells. HBV replication and antigens expression were determined in relation to the infection and culture conditions. RESULTS: In RC-HBV-Bac infected HepG2 cells, HBsAg, HBeAg and HBcAg were expressed in the cytoplasm and nuclei, and secreted into the medium. HBV replication was evidenced by the presence of a replication complex and covalently closed circular (ccc) DNA in the cytoplasmic fraction of infected cells. The level of HBV expression was directly proportional to the multiplication of RC-HBV-Bac infection. Polyethylene glycol was able to enhance the infection efficiency of the baculovirus to HepG2 cells. High levels of HBV replication were achieved under culture conditions supplemented with dimethyl sulfoxide and a low serum concentration. CONCLUSION: This in vitro model of hepatitis B, generated by baculovirus gene delivery, represents a simple and flexible system for the study of HBV replication and drug testing.
Baculoviridae* ; Cytoplasm ; Dimethyl Sulfoxide ; DNA ; Gene Transfer Techniques* ; Genome ; Hep G2 Cells ; Hepatitis B Core Antigens ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Models, Animal ; Polyethylene Glycols

<b>OBJECTIVEb>To observe the HBV serum markers and HBV DNA expressions of the neonates born to the HBsAg-positive mothers.

<b>METHODSb>By detecting serum immunity markers of hepatitis B virus (5 items) and serum HBV DNA of 283 neonates (a pair of twins) born to 282 HBsAg-positive mothers.

<b>RESULTSb>12 patterns emerge from the study of the hepatitis B serum markers of 283 neonates. Topping the list is the combination of HBeAg and anti-HBc positive accounting for 48.41% (137/283), followed by the combination of anti-HBe and anti-HBc positive accounting for 22.26% (62/283). The third highest combination is that of HBsAg, HBeAg and anti-HBc positive accounting for 12.37% (35/283). There are five combinations accounting for 16.61% (47/283), each with HBsAg-positive. No case is found of the five items all negative or only HBsAb positive. Five cases are detected of serum HBV DNA > or = 1 x 103 IU/ml accounting for 1.77%.

<b>CONCLUSIONSb>Neonates born to HBsAg-positive mothers display complex patterns of serum hepatitis B markers, the dominant pattern being the combination of HBeAg and anti-HBc positive. Cases of serum HBV DNA > or = 1 x 10(3) IU/ml are rare.

Biomarkers ; blood ; DNA, Viral ; analysis ; Female ; Hepatitis B ; transmission ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Male

BACKGROUND: Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables. METHODS: One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods. RESULTS: HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = -0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r = -0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005). CONCLUSIONS: HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy. TRIAL REGISTRATION Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1.
Antiviral Agents/therapeutic use* ; Biomarkers ; China ; DNA, Viral ; Hepatitis B Core Antigens/therapeutic use* ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Virus Replication

No abstract available.
Hepatitis B e Antigens* ; Hepatitis B Surface Antigens* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis*

No Abstract Available.
Hepatitis B e Antigens* ; Hepatitis B Surface Antigens*