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

Adult ; Female ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B, Chronic ; drug therapy ; immunology ; virology ; Humans ; Liver ; metabolism ; Male ; Middle Aged ; Vidarabine ; therapeutic use

The infection of Hepatitis B virus (HBV) can result in severe consequences, including chronic hepatitis, liver fibrosis, cirrhosis, and even liver cancer. Effective antiviral treatment has the potential to slow down the progression of the disease. HBV serum biomarkers play a crucial role in the dynamic management of chronic hepatitis B (CHB) patients. However, the conventional hepatitis B virus markers, such as hepatitis B serologic testing and HBV DNA, are insufficient to meet the clinical requirements. This review provided a comprehensive overview of the current research on the quantification of HBsAg and anti-HBc, HBV RNA and HBV core-associated antigen, which summarized the crucial role these markers play in the administration of antiviral medications, predicting the efficacy of treatment and anticipating the likelihood of virologic rebound following drug cessation, as well as assessing disease progression in CHB patients.
Humans ; Hepatitis B virus/genetics* ; Clinical Relevance ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B Core Antigens/therapeutic use* ; Biomarkers ; Liver Cirrhosis/drug therapy* ; Antiviral Agents/therapeutic use* ; Hepatitis B Surface Antigens/therapeutic use* ; DNA, Viral/therapeutic use* ; Hepatitis B e Antigens/therapeutic use* ; Hepatitis B/drug therapy*

<b>BACKGROUNDb>To investigate the immunological and virological efficacy of the therapeutic vaccine HBV CS1, a recombinant fusion protein which is composed of HBV core aa 1-155 plus PreS1 aa 3-55,against chronic HBV infection.

<b>METHODSb>HBV transgenic mice were immunized with HBV CS1(5 ug) emulsified in equal volume of complete Freund adjuvant on day 0, followed by a second vaccination with HBV CS1(5 ug) emulsified with incomplete Freund adjuvant on days 21. Mice of control group were mock-vaccinated with PBS plus complete Freund adjuvant/incomplete Freund adjuvant. The splenocytes of individual mouse were subjected to T cell proliferation assays by using 3Hg thymidine, HBsAg and HBV DNA in sera of mice were detected by ELISA and quantitative PCR, respectively.

<b>RESULTSb>HBV CS1 specific T cell response were induced in mice immunized with HBV CS1, with the titer of HBsAg and the level of HBV DNA decreased significantly after twice immunization with HBV CS1, while the control group almost remained the same.

<b>CONCLUSIONb>HBV CS1 has the immunological and virological efficacy against chronic HBV infection in HBV transgenic mice; HBV CS1 could represent candidate vaccine for further studies on its role as therapeutic vaccine against HBV chronic infection in human.

Animals ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; genetics ; immunology ; therapeutic use ; Hepatitis B Surface Antigens ; genetics ; immunology ; therapeutic use ; Hepatitis B Vaccines ; genetics ; immunology ; therapeutic use ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Immunization ; Male ; Mice ; Mice, Transgenic ; Protein Precursors ; genetics ; immunology ; therapeutic use ; Random Allocation ; Recombinant Fusion Proteins ; genetics ; immunology ; therapeutic use

<b>OBJECTIVEb>To evaluate the clinical efficacy of combined treatment with lamivudine and famciclovir on chronic hepatitis B virus (HBV) infection.

<b>METHODSb>Ninety patients with chronic HBV infection were divided into 3 groups. Group one had 28 patients and was treated with combination of lamivudine (0.1 g/d, PO) and famciclovir (1.5 g/d,PO) for 24 weeks. Group two and three had 30 and 32 cases, respectively, and were treated with lamivudine 100 mg/day PO and famciclovir (1.5 g/d,PO) alone. All the patients had positive markers of HBsAg, HBeAg and anti-HBcAg in serum assayed by ELISA and of HBV DNA tested by PCR.

<b>RESULTSb>Three strategies of treatment had no different effects on the change of patients' ALT levels. The serum HBV DNA became negative after treatment in 89.3% (25/28) of patients treated with combination of lamivudine and famciclovir, 66.7% (20/30) of patients treated with lamivudine, and 40.6% (13/32) of patients treated with famciclovir. The rate of serum HBeAg loss in 3 groups were 28.6% (8/28), 23.3% (7/30) and 21.9% (7/32), respectively.

<b>CONCLUSIONSb>The combination treatment of lamivudine and famciclovir for chronic HBV infection is safer than and superior to that of either drug alone.

2-Aminopurine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Child ; Drug Therapy, Combination ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; Hepatitis B virus ; immunology ; isolation & purification ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged

<b>OBJECTIVEb>To observe the effect of Yugan Granule (YGG) in treating patients of chronic hepatitis B infected with basic core promoter (BCP) mutant HBV.

<b>METHODSb>BCP mutation was detected by microwell liquid hybridization combined with enzyme linked immunosorbent assay (ELISA) and 46 patients were confirmed to be the mutant positive (Group A), and 69 the mutant negative (Group B). All patients were treated by YGG and the clinical symptoms and laboratory parameters before and after treatment were observed.

<b>RESULTSb>The scores of symptoms and serum levels of alanine transaminase (ALT) and total bilirubin (TBil) were decreased markedly in both groups after treatment. The HBeAg negative conversion rate in Group A was 60%, obviously higher than that in Group B (30%, P < 0.05), while HBV-DNA negative conversion rate between the two groups had the insignificant difference. The overall efficacy was similar in the two groups.

<b>CONCLUSIONb>YGG could remarkably alleviate the symptoms, reduce serum levels of ALT and TBil, and showed the effect of anti-HBV with the same efficacy both to BCP mutant and wild strain HBV infected patients.

Adolescent ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; immunology ; virology ; Humans ; Male ; Middle Aged ; Phytotherapy ; Point Mutation ; Promoter Regions, Genetic ; genetics ; Viral Core Proteins ; genetics

<b>OBJECTIVEb>To analyze the liver function in patients with diffuse large B-cell lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP regimens.

<b>METHODSb>In this retrospective study, 86 DLBCL patients, who were HBsAg-/HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2008. The patients were given at least two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti-HBV treatment, and followed-up for at least 12 months after completion of therapy.

<b>RESULTSb>Forty-seven patients received CHOP-like regimen while 39 patients received R-CHOP-like regimen. There were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group after the 1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%, P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively). Meanwhile, there were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th month, 7th-9th month and 10th-12th month after completion of therapy (7.7% - 40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05).

<b>CONCLUSIONSb>The present study reveals a low incidence of liver dysfunction in HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may indicate a potential low incidence of HBV reactivation in these groups, and Rituximab do not increase the rate of liver dysfunction. Therefore, these data may not support regularly prophylactic antiviral therapy during chemotherapy, but close monitoring of liver function, HBV serum markers and HBV DNA level are demanded.

Alanine Transaminase ; blood ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Hepatitis B Antibodies ; metabolism ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; metabolism ; Humans ; Liver Function Tests ; Lymphoma, Large B-Cell, Diffuse ; blood ; drug therapy ; immunology ; virology ; Male ; Prednisolone ; therapeutic use ; Prednisone ; therapeutic use ; Retrospective Studies ; Vincristine ; therapeutic use

BACKGROUND/AIMS: The widespread use of cytotoxic chemotherapy and immunosuppressants has resulted in reactivation of hepatitis B virus (HBV) recently becoming an issue. Although rituximab (an anti-CD20 monoclonal antibody) has revolutionized the treatment of lymphoma, recent reports have suggested that rituximab therapy increases the risk of viral-mediated complications, and particularly HBV reactivation. This study analyzed real clinical practice data for rituximab-related HBV reactivation. METHODS: Between January 2005 and December 2011, 169 patients received treatment with rituximab. Screening status of the HBV infection and frequency of preemptive therapy were determined in these patients, and the clinical features of HBV reactivation were analyzed. RESULTS: Seventy-nine of the 169 patients with chronic or past HBV infection were selected for evaluation of HBV reactivation. Of the 90 patients who were excluded, 22 (13.0%) were not assessed for HBsAg and anti-HBc, and 14 (8.3%) were not assessed for anti-HBc due to seronegativity for HBsAg. The selected patients were divided into those with chronic HBV infection (n=12) and those with past HBV infection (n=67); six patients (7.6%) experienced HBV reactivation. Eight patients received preemptive therapy, but three patients (37.5%) underwent HBV reactivation. Although HBsAg seropositivity was an independent risk factor for HBV reactivation (P=0.038), of the six patients with HBV reactivation, two (33.3%) had past HBV infection and three (50%) died of liver failure. CONCLUSIONS: The findings of this study demonstrate that adherence to guidelines for screening and preemptive therapy for HBV reactivation was negligent among the included cohort. Attention should be paid to HBV reactivation in patients with past as well as chronic HBV infection during and after rituximab therapy.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; Antibodies, Monoclonal, Murine-Derived/*adverse effects/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Child ; Child, Preschool ; Hepatitis B/etiology/mortality/virology ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Humans ; Lymphoma/*drug therapy ; Middle Aged ; Odds Ratio ; Retrospective Studies ; Risk Factors ; *Virus Activation ; Young Adult

BACKGROUNDS/AIMS: Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment. METHODS: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis. RESULTS: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAg-negative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01). CONCLUSIONS: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment.
Adult ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Female ; Hepatitis B Core Antigens/*analysis/metabolism ; Hepatitis B e Antigens/metabolism ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Lamivudine/*therapeutic use ; Male ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies

Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual's HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
Antiviral Agents/therapeutic use ; Autoimmune Diseases/complications/pathology ; Hematopoietic Stem Cell Transplantation ; Hepatitis B/complications/drug therapy ; Hepatitis B Core Antigens/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Virus Activation/*physiology