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

As part of the immunoserology program of the Korean Association of External Quality Assessment Service, we organized two trials on the external quality assessment of hepatitis viral markers in 2016 and 2017. The hepatitis viral antigens and antibodies program consisted of 10 test items. We delivered two and three types of pooled sera specimens to 965 and 965 institutions for the first and second trials of external proficiency testing in 2016, respectively. The number of participating laboratories was 915 (94.8%) and 913 (95.0%) in the first and second trials in 2016, respectively. We also delivered three kinds of pooled sera specimens to 936 and 1,015 institutions for the first and second trials of external proficiency testing in 2017, respectively. The number of participating laboratories was 920 (98.3%) and 996 (98.1%) in the first and second trials in 2017, respectively. The most commonly tested items were hepatitis B surface antigen, followed by the antibodies to hepatitis B surface antigen, anti-hepatitis C virus, hepatitis B envelope antigen, antibodies to hepatitis B envelope antigen, anti-hepatitis A virus and antibodies to hepatitis B core antigen. The most frequently used methods for detecting viral markers were the chemiluminescence immunoassay and the electrochemiluminescence immunoassay, but they yielded a few-false positive results due to the matrix effect. The immunochromatographic assay yielded false-negative results for anti-hepatitis A virus due to low sensitivity. Continuous improvement in the quality of viral hepatitis testing through participation in the survey seems necessary.
Antibodies ; Antigens, Viral ; Biomarkers* ; Hepatitis A ; Hepatitis B ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis C ; Hepatitis* ; Immunoassay ; Immunochromatography ; Korea* ; Laboratory Proficiency Testing ; Luminescence

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: Reactivation of hepatitis B virus (HBV) has been reported in HBV surface antigen (HBsAg)-positive patients undergoing chemotherapy, as well as HBsAg-negative patients with antibodies against HBV core antigen (HBcAg) and/or HBsAg (HBsAb). Chemotherapy-including rituximab-has recently been identified as a predictive factor for HBV reactivation in HBsAg-negative patients with malignant lymphoma. The aim of our study was to identify the factors predictive of HBV reactivation after chemotherapy in patients with malignant lymphoma. METHODS: We conducted a retrospective analysis of medical records from patients diagnosed with malignant lymphoma at Gachon University Gil Medical Center in City, County from January 2005 to December 2010. We subsequently determined HBsAg, HBsAb and anti-HBc status in the 196 patients treated with chemotherapy. RESULTS: The mean age of the patients was 57.3 +/- 14.5 years; 56.3% were male. A total of 172 of 196 (88%) patients in the study population were HBsAg (+) prior to chemotherapy. Three patients (3/11, 27.3%) in the HBsAg (+) group had confirmed HBV reactivation after chemotherapy. In addition, 26 of 196 (13%) patients in the study population tested HBcAg (+) positive prior to chemotherapy. One patient (1/15, 6.7%) in the HBsAg (-)/HBcAb (+) group had confirmed HBV reactivation. In the four patients with HBV reactivation, infection was resolved after treatment with 0.5 mg entecavir or 100 mg lamivudine. CONCLUSIONS: Reactivation of HBV after systemic chemotherapy can occur in HBsAg (-) patients. We recommend that malignant lymphoma patients undergoing chemotherapy be screened for HBV infection status, including HBcAg, and followed closely to prevent HBV reactivation.
Antibodies ; Antigens, Surface ; Drug Therapy* ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Lamivudine ; Lymphoma* ; Male ; Medical Records ; Retrospective Studies

BACKGROUND: Cutaneous vasculitis associated with viral hepatitis seems to occur as a hypersensitivity reaction against the circulating viral antigens. Hepatitis B virus(HBV)-encoded X antigen(HBxAg) is known to participate in the carcinogenesis of hepatocellular carcinoma(HCC) by the inactivation of p53. However, HBxAg has been found in chronic infiammatory lesions without the overexpression of p53. Accordingly, not only EBsAg and HBcAg but also HBxAg may be involved in HCC-associated cutaneous vasculitis, regardless of the alteration of p53. OBJECTIVE: This study was conducted to investigate the expression of HBV-encoded antigens in cutaneous vasculitis accompanied by HBV hepatopathy. Additionally, we have compared the expression of 3 HBV antigens and p53 between vasculitic patients with HCC and in others showing HCC-non-associated vasculitis. METHODS: Immunohistochemically, we examined the expression of HBsAg, HBcAg, and HBxAg in the tissue specimens taken from the vasculitic lesions of the 33 HBsAg-positive enrolled patients with cutaneous vasculitis proven by skin biopsy. RESULTS: 1. The immunohistochemical positivity rate to HBsAg in vasculitic patients with HBV hepatopathy was 66.7% overall. It was 90% in HCC-associated vasculitic subjects and 56.5% in the vasculitic subjects without HCC, respectively. 2. We found the expression of HBxAg in 80% of the vasculitic subjects showing HCC. The vasculitic patients without HCC showed 17,3% of the positivity rate to HBxAg. 3. We could not find the overexpression of p53 in the vasculitic tissue specimens of the HCC patients without the cutaneous metastasis from primary HCC. CONCLUSION: HBsAg, HBcAg and HBxAg may participate in the pathogenesis of cutaneous vasculitis with HBV hepatopathy, regardless of tumorigenesis.
Antigens, Viral ; Biopsy ; Carcinogenesis ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Hypersensitivity ; Neoplasm Metastasis ; Skin ; Vasculitis*

Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and in vivo imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.
Animals ; Hepatitis B/drug therapy* ; Hepatitis B Core Antigens ; Indocyanine Green/chemistry* ; Mice ; Nanoparticles/chemistry* ; Viral Core Proteins

BACKGROUND/AIMS: Testing for hepatitis B virus (HBV) serologic markers and appropriate vaccination are required in the management of inflammatory bowel disease (IBD) patients. We evaluated immunogenicity for HBV in IBD patients and the response to the HBV vaccination. METHODS: From May 2014 to August 2016, patients diagnosed with IBD were prospectively included and evaluated for antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. Among the 73 patients who were confirmed with nonimmunity to HBV, 44 patients who had completed the 3-dose HBV vaccination series received a single booster vaccination, while 29 patients who had not completed the vaccinations series or were unsure of receiving the vaccination received a full vaccination series. RESULTS: An optimal response was obtained in 70.5% of the patients in the booster group, and 89.7% of the patients in the full vaccination group. Age younger than 26 years (odds ratio [OR], 6.01; 95% confidence interval [CI], 1.15–31.32; P=0.033) and a complete previous vaccination series (OR, 0.15; 95% CI, 0.03–0.80; P=0.026) were associated with optimal vaccine response. Previous complete vaccination series (OR, 0.11; 95% CI, 0.02–0.73; P=0.022) was the only predictive factor for lower compliance. CONCLUSIONS: The response to the HBV vaccination was lower in patients older than 26 years and for those patients with a complete vaccination history. Since patients with a complete vaccination history also had poor compliance, serum HBV-titers should be checked more thoroughly, and a full vaccination series should be administered in cases when there is a negative response to the booster vaccination.
Compliance ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Inflammatory Bowel Diseases* ; Korea* ; Observational Study* ; Prospective Studies* ; Vaccination*

BACKGROUND: Cutaneous vasculitis associated with viral hepatitis seems to occur as a hypersensitivity reaction against the circulating viral antigens. Hepatitis B virus(HBV)-encoded X antigen(HBxAg) is known to participate in the carcinogenesis of hepatocellular carcinoma(HCC) by the inactivation of p53. However, HBxAg has been found in chronic infiammatory lesions without the overexpression of p53. Accordingly, not only EBsAg and HBcAg but also HBxAg may be involved in HCC-associated cutaneous vasculitis, regardless of the alteration of p53. OBJECTIVE: This study was conducted to investigate the expression of HBV-encoded antigens in cutaneous vasculitis accompanied by HBV hepatopathy. Additionally, we have compared the expression of 3 HBV antigens and p53 between vasculitic patients with HCC and in others showing HCC-non-associated vasculitis. METHODS: Immunohistochemically, we examined the expression of HBsAg, HBcAg, and HBxAg in the tissue specimens taken from the vasculitic lesions of the 33 HBsAg-positive enrolled patients with cutaneous vasculitis proven by skin biopsy. RESULTS: 1. The immunohistochemical positivity rate to HBsAg in vasculitic patients with HBV hepatopathy was 66.7% overall. It was 90% in HCC-associated vasculitic subjects and 56.5% in the vasculitic subjects without HCC, respectively. 2. We found the expression of HBxAg in 80% of the vasculitic subjects showing HCC. The vasculitic patients without HCC showed 17,3% of the positivity rate to HBxAg. 3. We could not find the overexpression of p53 in the vasculitic tissue specimens of the HCC patients without the cutaneous metastasis from primary HCC. CONCLUSION: HBsAg, HBcAg and HBxAg may participate in the pathogenesis of cutaneous vasculitis with HBV hepatopathy, regardless of tumorigenesis.
Antigens, Viral ; Biopsy ; Carcinogenesis ; Hepatitis ; Hepatitis B ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Humans* ; Hypersensitivity ; Malassezia* ; Neoplasm Metastasis ; Skin* ; Vasculitis ; Yeasts*

Hepatitis B Core Antigens ; immunology ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; virology ; Humans ; T-Lymphocytes, Cytotoxic ; immunology

<b>OBJECTIVEb>To explore the variations of gene C in hepatitis B viruses between hepatitis B patients and healthy carriers, and provide experimental evidences for analysis of virus gene mutations acting on the virus material science and response of the body to the virus.

<b>METHODSb>The virus DNA load in hepatitis B patients and healthy blood donors was investigated by real-time polymerase chain reaction (PCR). Gene sequence analysis was taken to detect gene polymorphism, and all the success samples were compaired with standard strain by DNAstar.

<b>RESULTSb>(1)G Compared with standard strain, C region in all samples had mutations, there were 31 mutations in at least 2 samples (3 mutations in gene PreC and 28 mutations in gene C), including 9 missense mutations, 1 chain termination mutation and 21 synonymous mutation. Mutations nt 1827 c-->a and nt 2221 c-->t existed in all the samples, and most samples had 6 synonymous mutations. Four hepatitis B patients had mutation nt1896 g-->a, and another 4 patients had 2 mutations, namely, S87G and I97F (or 197L) in HBcAg CTL recognition episome. (2) The success ratio of amplification and sequencing of HBV DNA was closely associated with its copy numbers. In the present study, copy numbers of HBV DNA which were successfully amplified and sequenced were almost more than 40 193/ml.

<b>CONCLUSIONSb>HBV genome were easily affected by nucleotide mutations, 2 residues had mutations in gene of C region, which is firstly reported, suggesting these mutations may be geographical restricted. Mutations in gene of C region may either change the structure and function of HBeAg and HBcAg, which may further induce the escape of immune clearance for HBV or influence the detection of HBsAg or HBeAg, which may creat new problems for the prevention, diagnosis and treatment of hepatitis B.

Female ; Hepatitis B ; virology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; isolation & purification ; Humans ; Male ; Mutation ; Polymorphism, Genetic