1.Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients.
Sun Young YIM ; Tae Hyung KIM ; Suh Sang JUN ; Eun Sun KIM ; Bora KEUM ; Yeon Seok SEO ; Hyung Joon YIM ; Yoon Tae JEEN ; Hoon Jai CHUN ; Hong Sik LEE ; Soon Ho UM ; Chang Duck KIM ; Nam Hee WON ; Ho Sang RYU
Gut and Liver 2017;11(3):417-425
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
2.The Correlation Between The Histologic Activity and Fibrosis and The Distribution of Intrahepatic HBsAg and HBcAg in Patients With Chronic Hepatitis B.
Kwang Bum CHO ; Jung Ho SOHN ; Kyung Sik PARK ; Du Young KWON ; Jae Seok HWANG ; Jung Wook HUR ; Sung Hoon AHN ; Soong Kuk PARK ; Sang Pyo KIM
The Korean Journal of Hepatology 2001;7(4):401-412
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
3.Associations of Expressions of HBcAg and HBsAg with the Histologic Activity of Liver Disease and Viral Replication.
Myung Su SON ; Jeong Hwan YOO ; Chang Il KWON ; Kwang Hyun KO ; Sung Pyo HONG ; Seong Gyu HWANG ; Pil Won PARK ; Choong Kee PARK ; Kyu Sung RIM
Gut and Liver 2008;2(3):166-173
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
5.The characteristic of T cells response to HBV-specific antigen proteins in patients with HBV infection.
Xi FENG ; Hui-Ping YAN ; Hui-Yu LIAO ; Yan-Min LIU ; Guo-Yuan ZHANG ; Fang LIN ; Yan ZHAO ; Yun-Li HUANG
Chinese Journal of Experimental and Clinical Virology 2012;26(4):253-255
<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
6.Study on HBV Gene Replication and Expression of Experimental Hepatitis B Model Using Baculovirus Gene Delivery System.
Woo Jong LEE ; Young Il YANG ; Won Hee JANG ; Seok Jae LEE ; Won Woon KIM ; Chang Soo CHOI ; Young Kil CHOI
Journal of the Korean Surgical Society 2007;72(2):117-127
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
7.Analysis of the test results of HBV serum markers and HBV DNA of the neonates born to HBsAg-positive mothers.
Miao-Chan WANG ; Ai-Fang XU ; Yong-Le ZHANG ; Dong-Ming XU
Chinese Journal of Experimental and Clinical Virology 2011;25(6):445-447
<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
8.Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients.
Jun LI ; Zhao WU ; Gui-Qiang WANG ; Hong ZHAO
Chinese Medical Journal 2021;134(10):1160-1167
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
9.A study on the relationship between HBeAg and hepatitis B virus DNAamong healthy HBsAg carries.
Yoo Sik HAHM ; Hai Rim SHIN ; Hyung Jong PARK ; Sung Ryul KIM
Korean Journal of Epidemiology 1992;14(1):48-58
No abstract available.
Hepatitis B e Antigens*
;
Hepatitis B Surface Antigens*
;
Hepatitis B virus*
;
Hepatitis B*
;
Hepatitis*
10.The Clinical significance of HBV markers in chronic HBsAg carrier: Titers of HBsAg, and HBeAg, and presence or absence of HBeAg and HBV-DNA.
Mi Kyeong OH ; Dong Jin LEE ; Joo Hyun HAN ; Kung Soo CHON ; Jong Sung KIM ; Kung Suk WON
Journal of the Korean Academy of Family Medicine 2000;21(10):1307-1316
No Abstract Available.
Hepatitis B e Antigens*
;
Hepatitis B Surface Antigens*