Research advances in persistent hepatitis B virus infection and its mechanism / 临床肝胆病杂志

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family and can cause acute and chronic hepatitis, liver cirrhosis, and even liver cancer in humans. Current antiviral drugs cannot completely eliminate HBV in liver cells and thus it is difficult to achieve a curative effect. In recent years, the mechanism of persistent HBV infection has attracted wide attention, which mainly involves host and virus. This article elaborates on the research advances in persistent HBV infection from the aspect of virus, including covalently closed circular DNA, HBV particles, and HBV components.

Hepatitis B virus X protein: The X factor in chronic hepatitis B virus disease progression

Introduction: Hepatitis B virus (HBV) is the most common aetiological factor causing hepatocellular carcinoma (HCC). HBx gene plays an enigmatic role in HBV-related HCC. In this study we have analysed amino acid substitutions in HBx from HBV-infected individuals of different clinical stages. Materials and Methods: HBV-infected individuals (n = 93) were recruited in the study. DNA was extracted from plasma, amplified, and DNA sequencing was performed using specific primers targeting HBx gene (540 bp). Results: Among the study participants, 57% had chronic HBV infection, 30% had chronic liver disease (CLD) and 13% had HBV related HCC. Genotypes such as D1, D2, D3, A1, C2 and B2 were identified of which genotype D2 was predominant (78%). HBxC-terminal deletion was observed in four hepatitis B e antigen (HBeAg) negative participants with CLD. The frequency of aminoacid substitution in proapoptotic domain was higher in HBeAg negative participants including I127V (34%), K130M (34%), V131I (40%). The frequency of double mutation (K130M+V131I) and triple mutation (I127V+K130M+V131I) were found to be higher (32% and 36%) in HBeAg negative participants. Also, we identified L5M substitution (4.3%) in HBeAg positive participants with advanced liver disease. Conclusion: In HBx gene, aminoacid substitutions at positions 127, 130, 131 are associated with poor expression of HBeAg. We suggest screening for HBx aminoacid substitutions especially in patients with HBeAg negative chronic HBV infection to predict the clinical outcome and enable early treatment to prevent disease progression.

Factors associated with efficacy of inucleoside analogues on sequential interferon therapy in HBeAg positive chronic hepatitis B patients / 中华实验和临床病毒学杂志

Objective@#To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg positive chronic hepatitis B (CHB) patients.@*Method@#HBeAg positive CHB patients treated with nucleoside analogue (NA) treatment received PEG-IFN α-2a 180 μg subcutaneously once weekly.NA was continually used with PEG-IFNα-2a during the first 12 weeks. HBsAg/HBeAg level and HBV DNA load were observed in the sequential pre-treatment (baseline) period, 12 th, 24 th, 36 th, 48 th and 72 nd weeks of sequential therapy in all patients.@*Result@#Of the 56 HBeAg-positive CHB patients, 5 (23.1%) achieved HBsAg loss/seroconversion, the baseline HBsAg level in HBsAg loss/seroconversion group was lower than that of the patients in the group that did not achieve HBsAg loss/seroconversion (2.750 lg IU/ml vs. 3.699 lg IU/ml, t=0.955, P=0.000); the difference was statistically significant in HBsAg decreased at the 12 th, 24 th, 36 th, 48 th week in the course of sequential therapy (0.913 vs 0.149, 2.847 vs 0.189, 4.378 vs 0.248, 4.587 vs 0.274 lg IU/ml) (t=-2.950, P=0.040; t=-8.732, P=0.009; t=-8.483, P=0.001; t=-8.214, P=0.003); 11(19.6%) achieved HBeAg loss/ seroconversion, the HBeAg baseline level in HBeAg loss/seroconversion group was lower than the patients in the group that not achieved HBeAg loss/seroconversion (1.217 lgS/CO vs 1.884 lgS/CO, t=2.061, P=0.044); the difference was statistically significant in HBsAg, HBeAg decreased at 24 th, 36 th, 48 th week in the course of sequential therapy between the two groups (1.330 vs 0.205, 2.084 vs 0.258, 1.972 vs 0.284, lg IU/ml; 1.168 vs 0.455, 1.363 vs 0.461, 1.177 vs 0.447, lg S/CO) (t=2.238, P=0.049; t=2.619, P=0.025; t=2.278, P=0.048); (t=2.273, P=0.043; t=3.415, P=0.001; t=2.271, P=0.049).@*Conclusions@#To HBeAg-positive CHB, lower baseline HBsAg, HBeAg level and HBsAg, HBeAg decreased earlier were could predict easier achievement of HBs(e)Ag loss/seroconversion.

Establish a predictive modeling under antiviral therapy for hepatitis B e antigen seroconversion in chronic hepatitis B / 中华肝脏病杂志

Objective@#To explore the predictive factors by demonstrating a predictive modeling under antiviral therapy for hepatitis B e antigen seroconversion in HBeAg-positive chronic hepatitis B patients.@*Methods@#198 cases with HBeAg-positive chronic hepatitis B were enrolled. Fatty liver, family history of hepatitis B, age, sex, drinking history, HBsAg, HBeAg, HBV-DNA levels, total bilirubin (TBil), CD4/CD8, albumin (ALB), alanine amino transferase (ALT) levels were used as a predictor variables of HBeAg seroconversion. Serological seroconversion of HBeAg was observed at 144 weeks of antiviral therapy. Predictive factors of HBeAg seroconversion was analyzed by logistic regression analysis, and the receiver operating characteristic curve was plotted.@*Results@#HBeAg seroconversion rate was 36.87%. Univariate analysis demonstrated that fatty liver (χ2 = 35.377; P < 0.001), family history of hepatitis B (χ2 = 15.687; P < 0.001), the levels of HBeAg (t = 5.034; P < 0.001), HBsAg (t = 3.454; P < 0.001) and HBV-DNA levels (Z = 4.651; P < 0.001) were predictor variables of HBeAg seroconversion. Multivariate analysis showed that family history of hepatitis B, fatty liver, HBV-DNA levels and HBeAg were independent predictors of HBeAg seroconversion. The established logistic regression model for HBeAg through regression analysis was logit P = 9.623-1.228 × family history of hepatitis B - 1.726 × fatty liver - 0.764 × HBV-DNA levels - 0.146 × HBeAg and area under curve was 0.875. When the cut-off value was -0.9350, the sensitivity and specificity were 92.70%, 75.50%, 83.22%, respectively.@*Conclusion@#Family history of hepatitis B, fatty liver, HBV-DNA levels and HBeAg may be independent predictors of HBeAg seroconversion at 144 weeks of antiviral therapy in HBeAg-positive chronic hepatitis B patients.

Study of sequential strategy for hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients with suboptimal early response to Peg-interferon-α / 中国基层医药

Objective To investigate the efficacy of entecavir (ETV) sequential therapy in the treatment of hepatitis B e antigen(HBeAg) positive chronic hepatitis B(CHB) patients with suboptimal early response to Peginterferon-α(Peg-IFN-α).Methods The cases of HBeAg-positive CHB who were treated with Peg-IFN-α for 12 to 24 weeks and serum HBsAg ＞ 20 000 IU/mL were enrolled into observation group.Treatment naive HBeAg positive CHB with serum HBsAg ＞ 20 000IU/mL were enrolled into control group.Both two groups received ETV for 96 weeks.Hepatitis B virus (HBV) virological and serological data were collected every 12 weeks.Results At the end of 48-week and 96-week,the rates of HBeAg seroconversion in the observation group were 23.3％ (10/43),30.2％ (13/43),respectively,which in the control group were 23.1％ (12/52),28.8％ (15/52),respectively.The HBsAg decline at 24-week was observed in both two groups.Conclusion Sequential strategy for patients with suboptimal early response to IFN is preferable.

Expression and clinical significance of liver tissue HBVcccDNA and serum markers for chronic hepatitis B antiviral treatment / 中国基层医药

Objective To investigate the expression and clinical significance of liver tissue hepatitis B virus covalently closed circular DNA ( HBV cccDNA) and three serum markers ( including serum HBV DNA, HBsAg, HBeAg) for chronic hepatitis B antiviral treatment.Methods 80 patients with chronic hepatitis B were collected, they were treated with telbivudine tablets,and the liver tissue HBVcccDNA and serum HBV DNA expression were detected by fluorescence quantitative PCR( FQ-PCR) .Serum HBsAg,HBeAg expressions were detected by enzyme linked immunosorbent assay ( ELISA) before treatment,12 weeks,28 weeks,44 weeks,52 weeks after treatment. Then,the correlation of liver tissue HBVcccDNA with serum markers was analyzed.Results Liver tissue HBVcccD-NA,serum DNA HBV,serum HBsAg and serum HBeAg were significantly decreased with the time of treatment,the differences were statistically significant(F=3.786,4.785,3.806,3.452,P=0.034,0.009,0.031,0.042),and the liver tissue HBVcccDNA, serum DNA HBV and serum HBeAg before treatment compared with after treatment had statistically significant differences(all P<0.05).And the differences of serum HBsAg in the treatment of 44 and 52 weeks compared with before treatment were statistically significant(all P<0.05).The results of correlation analy-sis showed that the expression of HBVcccDNA was positively correlated with serum HBV DNA and HBeAg ( r =0.674,0.672,P=0.015,0.036),and had no significant correlation with serum HBsAg expression(r=0.125,P=0.142 ) .Conclusion The expressions of serum HBV DNA and HBeAg could reflect HBVcccDNA expression of liver tissue,and the detection method is simple and non-invasive,which is worthy of recommendation in clinical.

Hepatic histological changes and its influencing factors of HBeAg negative chronic hepatitis B patients / 实用医学杂志

Objective To investigate hepatic histological features and its influencing factors of HBeAg-negative chronic hepatitis B patients. Methods 134 HBeAg-negative chronic hepatitis B (CHB) patients who underwent percutaneous liver biopsy were recruited in this study. The liver biopsy sections were examined after routine haematoxylin-eosin (HE) staining, and silver staining for assessment of fibrosis. The activity of liver disease was assessed by using a modified Knodell numeric histology activity index (HAI). ALT level, HBV DNA load, HBV serological markers, HBV genotype were assessed with appropriate methods. t test or analysis of variance was used to compare means. Non-parametric was done by Kruskal-Wallis test. The correlation between liver pathological change and clinical factors was analyzed by multivariate linear regression. Results Of 134 HBeAg negative CHB patients, percentages of mild (HAI 4 ~ 8), moderate (HAI 9 ~ 12), and severe hepatitis (HAI 13 ~ 18) were 26.9%, 26.1%, and 47.0%, respectively. As for hepatic fibrosis, 18.7% and 81.3% of the patients had fibrosis score < 3 and ≥3, respectively. Multivariate regression analysis showed that ALT level and hepatic fibrosis were correlated to hepatic inflammation (t = 6.687,P < 0.01; t = 3.478, P < 0.01) while age and hepatic inflammation activity were influencing factors of hepatic fibrosis (t = 3.587, P < 0.01; t =7.136, P < 0.01). However, correlation is not significant between hepatic histological change and other factors, including gender, HBVDNA, HBV genotype and HBeAb status. Conclusions In this study, hepatic histological change tend to become worse in majority of HBeAg-negative chronic hepatitis B , especially in older patients and those with high ALT level.

The effects of HBeAg and HBV DNA in chronic hepatitis B during late trimester of pregnancy on the postpartum hepatic inflammation / 国际检验医学杂志

Objective To explore the effects of hepatitis B e-antigen(HBeAg)and hepatitis B virus(HBV)DNA load during late trimester of pregnancy on postpartum chromic hepatitis B with acute exacerbation in female patients with chronic hepatitis B (CHB).Methods 1 14 cases of pregnant women with CHB treated in this hospital from March 2010 to June 2014 were selected and divided into the hepatitis B with acute exacerbation group and hepatitis B without acute exacerbation group.The general demograph-ic data and clinical information of these patients were collected,and serum HBV DNA loads and levels of alanine aminotransferase (ALT)were detected during late trimester of pregnancy(between the 28th to 36th weeks of pregnancy)and postpartum(6 to 12 weeks postpartum).The effects of HBeAg and HBV DNA loads on postpartum chromic hepatitis B with acute exacerbation were analysed.Results 24.6% of female patients was diagnosed with postpartum chromic hepatitis B with acute exacerbation.The inci-dence rate of postpartum chromic hepatitis B with acute exacerbation in female patients with positive HBeAg during late trimester of pregnancy increased,compared those with negative HBeAg,had statistically significant differences(P 0.05).The hepatic flare was correlated with the HBeAg status,but was not related with HBV DNA load.Conclusion Post-partum chromic hepatitis B with acute exacerbation might not be correlated with HBV DNA loads,but correlated with HBeAg, which indicates that positive HBeAg during late trimester of pregnancy could be a risk factor for postpartum chromic hepatitis B with acute exacerbation.

Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

BACKGROUND: Most mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters. METHODS: From 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters. RESULTS: Of the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL. CONCLUSIONS: We found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.

HBeAg quantification in predicting efficacy of pegylated interferon α therapy for patients with chronic hepatitis B / 中华临床感染病杂志

Objective To evaluate HBeAg quantification in predicting the efficacy of pegylated interferon (PegIFN) α treatment for patients with HBeAg-positive chronic hepatitis B (CHB).Methods A total of 216 HBeAg-positive CHB patients admitted in Ningbo No.2 Hospital during March 2009 and December 2011 were enrolled in the study.All patients were given subcutaneous injection of PegIFNα-2a or PegIFNα-2b weekly for 48 weeks and followed up for 24 weeks after discontinuation.Patients were divided into HBeAg seroconversion group and non-seroconversion group at the end of the follow-up.Receiver operating characteristic (ROC) curves were used to evaluate HBeAg levels at baseline and 12,24 weeks of treatment in predicting HBeAg seroconversion.Results HBeAg seroconversion was observed in 31.48％ (68/216) patients at the end of follow-up,and there was no significant difference in seroconversion rate between patients treated with PegIFNα-2a and those with PegIFNα-2b (32.00％ vs.29.27％,P ＞ 0.05).There was significant difference in baseline HBeAg levels between patients with HBeAg seroconversion and those without HBeAg seroconversion (Z =-3.834,P ＜ 0.05).HBeAg seroconversion patients had a tendency of rapidly decreasing HBeAg level,but there was no significant difference in decreasing rate between seroconversion and non-seroconversion patients (F =3.321,P ＞ 0.05).ROC curves showed that HBeAg level at 24-week was the best indicator for predicting HBeAg seroconversion with area under curve of 0.861.Conclusion Serum HBeAg level at 24-week of treatment may be used to predict the HBeAg seroconversion in HBeAg-positive CHB patients treated with PegIFNα.

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

BACKGROUND/AIMS: Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B. METHODS: We enrolled 91 patients with treatment-naive chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy. RESULTS: Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy. CONCLUSIONS: Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.

The correlation between HBeAg levels and entecavir long-term efficacy in chronic hepatitis B patients / 中华传染病杂志

Objective To study the correlation between HBeAg levels and the efficacy of entecavir long-term treatment in chronic hepatitis B (CHB) patients.Methods Fifty-nine HBeAgpositive CHB patients were divided into three groups according to baseline HBeAg levels:Group A (n=19,HBeAg≥1000 s/co),Group B (n=20,HBeAg 100 999 s/co) and Group C (n=20,HBeAg＜ 100 s/co).The HBeAg level at baseline and week 24 of entecavir treatment were retrospectively analyzed,and the correlation between changes of HBeAg level and efficacy of 144-week entecavir treatment was also analyzed.Data were analyzed by x2 test.Results There were no statistical differences of age and baseline alanine transaminase (ALT) levels among 3 groups,but hepatitis B virus (HBV) DNA level was correlated with HBeAg level.After 144 weeks of entecavir treatment,58 patients (58/59,98.3％) achieved ALT normahzation,56 (56/59,94.9％) achieved HBV DNA undetectable,30 (30/59,50.8％) achieved HBeAg loss,and 26 (26/59,44.1％)achieved HBeAg seroconversion.There were no statistical differences of ALT normalization rate and HBV DNA undetectable rate among three groups (x2 =2.4146,P=0.3427; x2 =2.2375,P=0.3267,respectively),while there were statistical differences of HBeAg loss rate and HBeAg seroconversion rate among three groups (x2=7.6484,P =0.0218; x2 =7.6455,P =0.0219,respectively).The HBeAg loss and HBeAg seroconversion rates in group C were 70.0％ and 65.0％,respectively,which were both higher than group B (55.0％ and 45.0％,respectively) and group A (26.3 ％ and 21.0 ％,respectively).Among 33 patients whose HBeAg levels declined ＞1 lg s/co after 24-week treatment,22 (66.7％) achieved HBeAg seroconversion after 144-week treatment,while only 4 (4/26,15.4％) achieved HBeAg seroconversion in other 26 patients (P＜0.01).Among 26 patients who achieved HBeAg seroconversion,20 had withdrawn entecavir therapy and 3 achieved HBsAg sero-clearanee.Conclusion In HBeAg positive CHB patients,the baseline HBeAg level,especially HBeAg level declining＞1 lg s/co after 24-week treatment have good predictive value for the 144 week efficacy of entecavir treatment,especially for HBeAg seroconversion.

The relationship between different serum HBeAg levels and pathological stages of patients with chronic hepatitis B / 中华传染病杂志

Objective To investigate the relationship between serum HBeAg level and inflammation grade (G)/fibrosis stage (S) in the liver tissues of chronic hepatitis B (CHB) patients in the immune clearance phase (IC). Methods Both liver biopsy samples and serum samples were consecutively collected from CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during March 2007 to June 2010.Electro-chemiluminescence and fluorogenic quantitative polymerase chain reaction (PCR) methods were used to determine HBeAg titer and hepatitis B virus (HBV) DNA level,respectively.The relationships between HBeAg titer and liver pathological stages were analyzed using Spearman rank correlation analysis.Receive operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBeAg for liver pathological stages.Results Totally 249 patients with CHB were enrolled into this study.The serum HBeAg absorbances in patients with liver inflammation G1 to G4 were (2.93±2.85),(2.96±2.74),(2.69±2.67) and (2.30±2.41) lg s/co,respectively,while those in patients with liver fibrosis S1 to S4 were (2.99±2.74),(2.89±2.73),(2.58±2.55) and (2.32±2.44) lg s/co,respectively,which indicated that serum HBeAg titers were significant different in patients with different grading and staging of liver tissues (x2 =47.13,P＜0.01; x2 =74.12,P＜0.01).Spearman rank correlation analysis showed that serum HBeAg titer was negatively correlated with inflammation grades and fibrosis stages of liver tissues (r=-0.418 and-0.532,respectively; both P＜0.01).ROC curve analysis revealed that the areas under the curve (AUC) were 0.74 (G≥≥3) and 0.73 (G≥4),and the HBeAg (s/co) cut-off values were 2.95 and 2.64 lg s/co,respectively.Similarly,ROC curve analysis revealed that the AUC were 0.80 (S≥3) and 0.77 S≥4),and the HBeAg cut-off values were 2.99 and 2.82 lg s/co,respectively.Conclusions The serum HBeAg titer is negatively correlated with the inflammation grades and fibrosis stages m liver tissues of CHB patients in IC phase.The level of HBeAg may be used as an adjunctive noninvasive marker to reflect the inflammation and fibrosis status in the liver.

Hepatitis B Precore Protein: Pathogenic Potential and Therapeutic Promise

Hepatitis B virus (HBV), a small and economically packaged double-stranded DNA virus, represents an enormous global health care burden. In spite of an effective vaccine, HBV is endemic in many countries. Chronic hepatitis B (CHB) results in the development of significant clinical outcomes such as liver disease and hepatocellular carcinoma (HCC), which are associated with high mortality rates. HBV is a non-cytopathic virus, with the host's immune response responsible for the associated liver damage. Indeed, HBV appears to be a master of manipulating and modulating the immune response to achieve persistent and chronic infection. The HBV precore protein or hepatitis B e antigen (HBeAg) is a key viral protein involved in these processes, for instance though the down-regulation of the innate immune response. The development of new therapies that target viral proteins, such as HBeAg, which regulates of the immune system, may offer a new wave of potential therapeutics to circumvent progression to CHB and liver disease.

Relationship of circulating Thl7/Treg ratio with hepatitis B e-antigen loss in chronic HBV infection patients receiving enticarvir(ETV) antiviral treatment / 第二军医大学学报

Objective: To investigate the relation of Treg/Th17 ratio with HBeAg loss in chronic HBV infection patients during enticarvir antiviral treatment. Methods: The sera and peripheral blood mononuclear cells (PBMCs) were obtained from the enrolled chronic HBV infection patients and healthy controls at different time points of enticarvir antiviral treatment. The HBV markers, HBV-DNA, serum alanine transaminase(ALT), the HBV-specific IL-17 levels, and the frequencies of Th17, Treg cells in PBMCs were determined. Results: HBV-DNA and Treg cell frequencies were decreased and the frequency of Th17 cells was rapidly increased in all patients; the secretion of IL-17 decreased upon specific stimulation with HBcAg. Therapy induced inhibition of HBV replication led to great decrease of Treg/Th17. The decrease of Treg/Th17 ratio was closely related to loss of serum HBeAg at the fourth week. Conclusion: Inhibition of viral replication can not only reduce the activity of Th17 cells, but also quickly decrease the Treg/Th17 ratio. The Treg/Th17 ratio at the fourth week can serve as a marker for the effect of entacavir treatment for chronic hepatitis B.

Combination of interferon α with mannan peptide in treatment of HBeAg-positive chronic hepatitis B / 中华临床感染病杂志

Objective To investigate the clinical effect of IFNα combined with mannan peptide in treatment of patients with HBeAg-positive chronic hepatitis B ( CHB ). Methods Eighty HBeAg-positive CHB patients with HBV DNA quantity ranging from 10 to 10 eopies/mL were enrolled and randomized into the treatment group and the control group ( n = 40 for each ). Patients in treatment group were given daily subcutaneous injection of IFNα-2b 5,000,000 U for 52 weeks, and received mannan peptide 10 mg per intravenous injection or 2. 5 mg per intramuscular injection for a total of 2 to 3 treatment courses (12 weeks for each). The control group received only IFNα-2b treatment. Liver function, serum markers of hepatitis B, HBV DNA quantity and blood tests were performed before the treatment and at 2, 4, 8, 16, 26 and 52-week during the treatment; and the adverse effects were recorded. Results The rates for ALT normalization, negative HBsAg, negative HBeAg, HBeAg seroconversion and negative HBV DNA were 91. 8% , 17. 5% , 52. 5% , 27. 5 % and 47. 5% at 52nd week in the treatment group, while those in the control group were 80. 0% , 12. 5% , 30. 0% , 10. 0 % and 25. 0% , respectively. There were significant differences in HBeAg-negative, HBeAg-seroeonversion and HBV DNA-negative rates between two groups (χ2 = 4. 178, 4.021 and 4.381, P < 0. 05 ) , and these indexes in the treatment group were increased to 57. 5% , 30. 0% and 50. 0 respectively at 52nd week after drug withdraw. White blood cells began to be elevated at 4th week and were restored to the normal levels at 8th week in the treatment group, while the count in the control was lower than the normal value even at 52nd week of the treatment with the average of (3.45±1. 18)×109/L. Conclusion Alpha-interferon combined with mannan peptide therapy is effective for patients with HBeAg-positive CHB, which may restore the declined peripheral WBC counts induced by interferon and improve the compliance.

Trend of clinical diagnosis of hepatitis B virus: quantity and standardization / 中华检验医学杂志

spective application of detection of HBV virological and serological markers, and their use in clinic.

Clinical Outcomes of Lamivudine Therapy in HBeAg Positive Chronic Hepatitis B with Minimally Elevated ALT / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to compare the efficacy of lamivudine therapy between chronic hepatitis B (CHB) patients, whose ALT levels less than 2 times the upper limit of normal (ULN) and patients whose ALT levels are more than 2 times ULN. METHODS: We retrospectively analyzed 508 consecutive patients with HBeAg-positive CHB who were treated with lamivudine for 1 year or more. Forty-six patients (Group A) with pretreatment ALT levels less than 2 times ULN were retrospectively compared with 462 patients (Group B) whose ALT levels are more than 2 times ULN. RESULTS: HBeAg seroconversion was achieved in 15 (32.6%) of group A and 162 (35.1%) of group B. The cumulative rates of HBeAg seroconversion in group A and B were 19% and 21% at 12 months; 35% and 31% at 24 months; and 38% and 39% at 36 months, respectively. HBV breakthrough was observed in 20 (43.5%) of group A and 192 (41.6%) of group B. The cumulative breakthrough rates of group A and B were 18% and 12% at 12 months; 33% and 29 % at 18 months; 45% and 42% at 24 months, respectively. Post-treatment relapse in group A and B occurred in 56% (5/9) and 41% (44/108), respectively. Therefore, the rates of the HBeAg seroconversion, breakthrough, and post-treatment relapse were not significantly different between these two groups. CONCLUSIONS: Lamivudine therapy in HBeAg-positive CHB patients whose ALT levels are minimally elevated is as effective as in treatment of the patients whose pretreated ALT levels are twice more than ULN.

The death indicators in hepatitis B e antigen-negative patients with liver cirrhosis / 中国实用内科杂志

ChildA (4.54%,x~2= 21.992,P=0.000);Among the HBeAg positive patients,the mortality of MELD≥ 18 patients (17.24%) was higher than the MELDChild A (0%,x~2= 5.363,P=0.021).Multivariate analysis showed that death rate was independently predicted by old age,higher Child -Pugh and the ALT persistent elevation in hepatitis B e antigen-negative patients with liver cirrhosis (P

Cloning and prokaryotic expression of a novel binding protein 1 of HBeAg / 解放军医学杂志

Objective To clone the human gene of Hepatitis B virus e antigen binding protein 1 (HBEBP1), which was screened with yeast two-hybrid system and bioinformatics techniques, to construct prokaryotic expression vector of pET-32a(+)-HBEBP1, and to induce the expression of recombinant protein in E. coli BL21. Methods The DNA fragment of HBEBP1 of about 372bp was amplified by reverse transcription PCR (RT-PCR), in which the mRNA was taken from HepG2 cells as the template, and cloned into pGEM-T vector. After restriction enzyme digestion identification and sequencing, the correct target DNA fragment was inserted into inducible prokaryotic expression vector pET-32a(+) and then transformed into competent E. coli BL21. By restriction enzyme digestion and PCR, the positive transformed clones were identified and induced with IPTG to obtain fusion protein. The HBEBP1 fusion protein was analyzed by Western blotting hybridization. Results The 372bp DNA fragment of HBEBP1 was amplified by RT-PCR. The recombinant expression vector pET-32a(+)-HBEBP1 was constructed successfully. After transformation with pET-32a(+)-HBEBP1 and induction with IPTG, the recombinant target protein of about 33kD was obtained, which was consistent with our anticipation. Western blotting assay showed that the protein had good specificity. Conclusions The recombinant prokaryotic expression vector pET-32a(+)-HBEBP1 is constructed, and the HBEBP1 gene is cloned successfully. The HBEBP1 fusion protein could be expressed in prokaryotic expression system of E. coli. These results lays a foundative for studying the immunogenicity and the biological characteristics of the HBEBP1 protein.