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.

Correlation between serum HBV DNA level and HBsAg titer in HBeAg-positive pregnant women and impact of genomic variability of hepatitis B virus pre S/S regions on their correlations / 中华肝脏病杂志

Objective@#To analyze the correlation between serum HBV DNA level and HBsAg titer in hepatitis B e antigen positive pregnant women without antiviral therapy, and investigate the impact of genomic variability of preS/S regions on their correlations.@*Methods@#Prenatal serum samples from 882 pregnant women with chronic HBV infection who were positive for HBsAg, HBeAg and HBV DNA and were not on antiviral therapy were included in the analysis. The Abbott i2000 and m2000 systems were used to qualitatively or quantitatively detect HBsAg, HBeAg and HBV DNA levels, respectively. HBV genotyping was performed using a type-specific primer nested polymerase chain reaction (nPCR). In addition, serum samples of pregnant women with HBV DNA levels correlated with HBsAg titer and HBV DNA levels higher than HBsAg titers were used to perform preS/S region amplification by nPCR method. PCR products were directly sequenced and mutation sites were analyzed by MEGA6.0 stasticial software. Mann-Whitney U test was used for the measurement data, and 2-test test for count data. Correlations between variables were analyzed using Spearman’s rank correlation.@*Results@#Serum HBsAg titer of HBeAg-positive pregnant women was positively correlated with HBV DNA level (r = 0.754, P < 0.01). Compared with the control group, mutation sites A60V (100% vs. 15.38%, χ2 = 7.61, P < 0.01), V90A (100% vs. 30.77%, χ2 = 4.43, P < 0.05) and I161T of HBV preS/S region (80.00% vs. 0, χ2 = 9.14, P < 0.01) showed a significant decrease in HBsAg titer.@*Conclusion@#Serum HBV DNA levels were positively correlated with HBsAg titer in HBeAg-positive pregnant women. Therefore, serum HBsAg titer may be used as a surrogate marker of serum HBV DNA. Single or multiple amino acid mutations sites A60V, V90A, and I161T in preS/S region may be one of the reasons that lead to a significant drop in HBsAg titer and affect its correlation with HBV DNA levels.

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.

Analysis on significance of HBV envelope large protein and its correlation with virus replication in patients with chronic hepatitis B / 国际检验医学杂志

Objective To analyze the relationship among serum hepatitis B virus (HBV ) envelope large protein (HBV‐LP ) , HBV‐DNA and HBV marker(HBV‐M ) for investigating the clinical significance of HBV‐LP to reflect the HBV in vivo replication in the patients with HBV infection .Methods Total 540 cases of chronic HBV infection treated in the Longgang District Hospital of Traditional Chinese Medicine from April 2013 to September 2015 were selected .The real‐time fluorescence quantitative PCR meth‐od was used to detect serum HBV‐DNA ,HBV‐LP and HBV‐M were detected by the enzyme linked immunosorbent assay (ELISA) . The correlation among HBV‐LP ,HBV‐M and HBV‐DNA were analyzed .Results The positive rate of HBV‐LP in HBeAg‐positive patients was 96 .39% ,and which of HBV‐DNA was 93 .33% ,there was no statistically significant difference between them (P>0 .05);The serum HBV‐LP level was positively related with the logarithmic value of HBV‐DNA copies ;the positive rate of HBV‐LP in HBeAg‐negative patients was 63 .33% ,and which of HBV‐DNA was 51 .11% ,the difference between them was statistically significant(P<0 .05) .Conclusion HBV‐LP can effectively reflect the HBV in vivo replication in the patients with chronic hepatitis B and its sensitivity is higher than that of HBeAg ,HBV‐LP can even more reflect the HBV in vivo replication status in patients with HBeAg‐negative chronic hepatitis B .

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.

Relationship between HBV genotype and liver damage in northern China / 国际检验医学杂志

Objective To discuss the relationship between hepatitis B virus (HBV) genotype and HBV DNA ,liver fibrosis ,liver function and HBeAg .Methods HBV genotypes ,HBV DNA ,liver fibrosis indicators and alanine aminotransferase(ALT ) ,aspartate aminotransferase(AST ) ,total bilirubin(TBIL) ,albumin(ALB) and HBV e antigen(HBeAg) were detected in patients with serum hepatitis .All data were statistically analyzed .Results There was no significant difference of HBV DNA ,ALT ,AST ,TBIL ,ALB , procollagen- Ⅲ -peptide ,type Ⅳ collagen ,hyaluronic acid and laminin between patients with B and C genotype infection (P> 0 .05) . However ,HBeAg level in patients with C genotype infection was higher than that in patients with B genotype infection (P< 0 .05) . Conclusion There might be no significant difference of HBV DNA ,liver function and liver fibrosis between patients with B and C genotype infection ,but HBeAg level in patients with C genotype infection could be higher than patients with B genotype infection .

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.

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.

Clinical effect of telbivudine in pregnant patients with e antigen-negative chronic hepatitis B / 中国基层医药

Objective To investigate clinical effect of telbivudine used in e antigen -negative chronic hepatitis B pregnant patients,to provide a reference for clinical treatment.Methods 90 pregnant patients with chronic hepatitis B e antigen -negative were selected,they were divided into two groups,50 patients in the control group and 40 patients in the observation group.The observation group used telbivudine treatment,the control group used the compound glycyrrhizin treatment.Before and after treatment,HBV DNA levels,negative rate,serum ALT levels,pregnancy outcome were compared between the two groups.Results After treatment,HBV -DNA in the two groups was significantly decreased compared with before treatment,before treatment,the HBV -DNA of the control group was (6.37 ± 1.18)mL,6 weeks after delivery was (5.49 ±1.21)mL;before treatment,the HBV -DNA of the observation group was (6.31 ±1.21)mL,6 weeks after delivery was (0.23 ±0.04)mL.The difference was statistically significant (t =8.154,P <0.01 ).In the observation group,before birth,six weeks after childbirth HBV -DNA were (0.21 ± 0.05)lg copy/mL,(0.23 ±0.04)lg copy/mL,which were significantly lower than those of the control group,the differences were significant (t =19.257,P =0.000;t =8.154,P =0.000).4 weeks,8 weeks after treatment,six weeks after childbirth,the HBV -DNA negative conversion rates of the control group were 52.00%,60.00%, 88.00%,which were significantly lower than the observation group (χ2 =177.61,142.41,184.58,P <0.01 ). Compared with before treatment,ALT levels after treatment were significantly decreased in the two groups (t =29.665,P <0.01).Before birth,six weeks after birth,ALT levels in the observation group were (12.58 ±2.58)U /L, (18.44 ±3.43)U /L,which were significantly lower than the control group (t =54.251,P =0.000;t =29.665,P =0.000).The incidence rate of adverse pregnancy of the observation group was 14.00%,compared with the control group the difference was not statistically significant (χ2 =0.524,P =0.493 ).Conclusion Telbivudine in the treatment of gestational e antigen -negative chronic hepatitis B pregnant patients has good clinical effect,it can help to control hepatitis activity and reduce virus levels,which is worthy of clinical application.

Analysis of abnormal Hepatitis B virus serological markers in neonatals / 临床儿科杂志

Objectives To investigate the outcomes of neonatals with abnormal hepatitis B virus (HBV) serological markers. Methods Twenty-eight neonatals who had abnormal HBV serological markers and whose mothers had positive HBsAg, HbeAg and HbcAb were studied. Among them, 21 neonatals who had positive HBsAg, HbeAg and HbcAb were included in vertical transmission group;7 neonatals who had positive HbeAg, HbcAb and negative HBsAg were included in suspicious group. The quantities of HBV serological markers were determined by time-resolved immunofluorometric assay (IFMA) and the level of HBV DNA were measured by fluorescence quantitative PCR (FQ-PCR). Results Serum HBeAg and HBsAg levels in suspi-cious group were lower than those in vertical transmission group (P<0.05). The results showed that HBeAg level (0.55 ± 0.19 PEIU/ml) three months after birth was lower than that (4.02 ± 2.00 PEIU/ml) 7 days after birth in suspicious group (P<0.05). Conclusions Early interference has positive effect in mothers and neonatls with abnormal HBV serological markers.

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.

Difference of Rh Phenotype between Irregular Antibody Positive Patients and RhD Positive Population in Korea / 대한수혈학회지

BACKGROUND: The Rh system is the most important blood group after ABO in the transfusion field. Nearly half of irregular antibodies with specificity are related to Rh antigens in Korea. Formation of alloantibody for red blood cells is considered variable according to Rh phenotype of patients. We therefore studied the significance of Rh phenotype in Korean irregular antibody positive patients. METHODS: We performed retrospective reviews for the results of antibody identification tests performed from Jun. 2004 to Nov. 2013 in our university medical center. Rh phenotype, direct antiglobulin test, and antibody specificity were investigated. Rh phenotype was tested using RhD+ phenotype ID-card (DiaMed GmBH, Switzerland). RESULTS: A total of 504 patients were included. Of 504 patients, 495 (98.2%) were RhD positive. The proportion of Rh phenotype differed significantly between irregular antibody positive patients and known RhD positive Korean population in CDe phenotype (59.0% vs 39.4%, P<0.0001) and CcDEe phenotype (22.6% vs 38.4%, P<0.0001), respectively. The percentage of other Rh phenotype was not different in two groups. Formation of anti-E antibody in E negative patients was significantly higher than that of anti-C formation in C negative patients (P<0.0001). Sixteen patients showed antibodies with specificity for their own Rh system antigens. CONCLUSION: A significant disproportion of Rh phenotype was observed between irregular antibody positive patients and RhD positive Korean population. There would be a difference of immunogenicity among C/c and E/e antigens. E antigen matching might be considered first for patient required chronic transfusion if additional RBC matching would be implemented.

Clinical observation of adefovir dipivoxil in the treatment of hepatitis B ptients with HBeAg positive / 中国基层医药

Objective To evaluate the safety and effect of adefovir dipivoxil (ADV) on hepatitis B in HBeAgpositive patients.Methods 131 patients were divided into two groups randomly.Two groups were treated with ADV (10mg/d)and matrine (0.6g/d),respectively.The rate of HBV negative,the normalization rates of ALT,HBeAg loss and anfi-HBe seroconversion were evaluated respectively.Results After 12 weeks of treatment,the rate of HBV negative,the normalization rates of ALT,HBeAg loss and anti-HBe seroconversion of ADV were all significantly higher than those of matrine group(53.2％ vs 7.8％,36.0％ vs 8.7％,13.6％ vs 3.1％,6.2％ vs 0,respectively,x2 =56.32,23.18,all P ＜ 0.01).Conclusion The domestic ADV superior to matrine in HBeAg-positive patients.

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.