Analysis of influencing factors of serum HBeAg loss in patients with chronic hepatitis B / 中国热带医学

@#Abstract: Objective To explore the influencing factors of serum HBeAg loss in patients with chronic hepatitis B (CHB) and and provide evidence for effective treatment of CHB. Methods A follow-up cohort of HBeAg-positive CHB patients was established in the the Infectious Diseases Outpatient Clinic of hospital. Regular follow-up and laboratory test indicators were collected to analyze the changes of serum HBeAg in HBeAg-positive CHB patients during the follow-up period. The subjects were divided into the case group (serum HBeAg loss) and the control group (serum HBeAg not loss) according to whether serum HBeAg loss occurred. The baseline data characteristics of the two groups were analyzed and compared, and the influencing factors of serum HBeAg loss were analyzed by Cox univariate and multivariate regression. Results A total of 634 HBeAg-positive CHB patients were enrolled, with a total follow-up of 2 570.01 person-years. Among them, 237 cases of serum HBeAg loss occurred, with the mean follow-up time of 40.92 months, and the rate of HBeAg loss was 9.22/100 person-years. There were significant differences in HBV family history, antiviral therapy, baseline WBC, PLT, ALT, AST, T˗Bil, GGT, AFP, quantitative HBsAg and quantitative HBeAg between serum HBeAg loss group and serum HBeAg not loss group (P<0.05). Cox regression analysis showed that family history of HBV (HR 0.68, 95％CI:0.50-0.92, P=0.012), ALT (HR2.06, 95％CI:1.52-2.79, P<0.001), quantitative HBsAg (HR 0.68, 95％CI:0.48-0.95, P=0.024), quantitative HBeAg (HR 0.48, 95％CI:0.31-0.74, P=0.001) were independent influencing factors for HBeAg loss in HBeAg-positive CHB patients. Conclusions HBeAg-positive CHB patients without family history of HBV, initial ALT≥80 U/L, quantitative HBsAg<1 000 IU/ml, quantitative HBeAg<1 000 C.O.I are more likely to have serum HBeAg loss.

Value of combined baseline serum HBV markers in predicting HBeAg seroconversion in chronic hepatitis B patients treated by nucleos(t)ide analogues / 临床肝胆病杂志

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Prognosis of acute-on-chronic liver failure caused by hepatitis recurrence after withdrawal of nucleos(t)ide analogues in chronic hepatitis B patients with different HBeAg status / 临床肝胆病杂志

Objective To investigate the difference in the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) caused by hepatitis recurrence after withdrawal of nucleos(t)ide analogues (NUC) and possible causes in HBeAg-positive versus HBeAg-negative chronic hepatitis B (CHB) patients. Methods A total of 108 CHB patients with HBV-ACLF caused by withdrawal of NUC who were admitted to The First Affiliated Hospital of Nanchang University from January 2017 to December 2018 were enrolled, and according to HBeAg status, these patients were divided into HBeAg-positive group with 57 patients and HBeAg-negative group with 51 patients. The two groups were compared in terms of sex, age, clinical manifestation, signs, levels of total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time, activated partial thromboplastin time, prothrombin time/international normalized ratio, and HBV DNA quantification on admission, complications (including hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis), and prognosis of HBV-ACLF. In addition, 48 CHB patients with continuous NUC antiviral therapy for > 2 years and HBV DNA < 20 IU/mL were enrolled, and the serum level of HBV pgRNA was measured to investigate the possible causes of the difference in the prognosis of HBV-ACLF between the patients with different HBeAg statuses. The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data. Results For the 108 patients with HBV-ACLF caused by drug withdrawal and recurrence, the HBeAg-positive group had an improvement rate of 49.1% and the HBeAg-negative group had an improvement rate of 74.5%. The HBeAg-negative group had a significantly higher improvement rate than the HBeAg-positive group ( χ 2 =2.811, P =0.006). The HBeAg-positive group had a significantly higher level of HBV DNA than the HBeAg-negative group on admission ( t =-3.138, P =0.002). For the 48 CHB patients who achieved virologic response after long-term antiviral therapy, the HBeAg-positive group had a significantly higher HBV pgRNA load than the HBeAg-negative group ( H =2.814, P =0.049). Conclusion Compared with the HBeAg-positive CHB patients, HBeAg-negative CHB patients have a significantly better improvement rate of HBV-ACLF caused by hepatitis recurrence after withdrawal of NUC antiviral therapy. The difference in baseline HBV pgRNA level may be associated with the difference in the prognosis of HBV-ACLF in patients with different HBeAg statuses.

Influencing factors for the functional cure of chronic hepatitis B and related mechanism / 临床肝胆病杂志

Functional cure of chronic hepatitis B (CHB), defined as negative hepatitis B surface antigen (HBsAg) with or without the presence of hepatitis B surface antibody (anti-HBs), is considered the optimal endpoint for CHB treatment at present. Studies have shown that HBsAg clearance can reduce the risk of HBV complications such as liver cirrhosis and hepatocellular carcinoma. However, HBsAg clearance rate remains at a relatively low level, which may be associated with the immune tolerance state caused by HBV infection. HBsAg clearance and/or the presence of anti-HBs indicate the partial recovery of HBV-specific immunity. This article discusses the influencing factors for the functional cure of CHB and the underlying mechanisms.

Value of HBsAg level in predicting liver inflammation in patients with HBeAg-positive chronic hepatitis B virus infection and normal alanine aminotransferase / 临床肝胆病杂志

Objective To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load. Methods A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t -test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index. Results There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ 2 =6.508, P =0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z =-3.344, P =0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z =-2.184, P =0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P =0.017), and the cutoff value of HBsAg was 33884.4I U/mL. Conclusion Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.

Expression level of serum HBV RNA in HBeAg-positive chronic hepatitis B patients at different periods and its value of measurement / 临床肝胆病杂志

Objective To investigate the expression level and potential clinical value of serum HBV RNA in HBeAg-positive chronic hepatitis B (CHB) patients at different periods. Methods A total of 61 CHB patients who attended the outpatient and inpatient services of Department of Hepatology, Hangzhou Xixi Hospital, from August 2019 to December 2020 were enrolled, and according to the antiviral therapy for HBeAg-positive CHB patients, they can be divided into group A with untreated HBeAg-positive CHB (HBeAg+ and HBV DNA+) patients, group B with treatment-experienced patients before HBeAg seroconversion (HBeAg+ and HBV DNA-), and group C with treatment-experienced patients after HBeAg seroconversion (HBeAg- and HBV DNA-). Peripheral blood HBV RNA load was measured at different periods, and its correlation with HBsAg and HBV DNA was analyzed. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups; a Pearson or Spearman correlation analysis was used to describe the correlation between two variables. Results The positive rates of HBV RNA in these three groups were 100% (22/22), 88.2% (15/17), and 22.7% (6/22), respectively. In group A, HBV RNA was positively correlated with HBsAg and HBV DNA ( r =0.612 and 0.922, both P < 0.01), while in groups B and C, there was no correlation between HBV RNA and HBsAg. Group B had significantly higher levels of HBV RNA and HBsAg than group C ( Z =-4.44 and -2.41, both P < 0.05). The HBV DNA-positive group had a significantly higher level of HBV RNA than the HBV DNA-negative group ( Z =-6.16, P < 0.01). Conclusion After HBV DNA clearance achieved by antiviral therapy with nucleos(t)ide analogues in CHB patients, serum HBV RNA can still be detected in some of these patients. Since HBV RNA only comes from cccDNA in the liver, it can better reflect viral replication activity in the liver than HBV DNA and thus has a certain clinical value in the management of CHB patients.

Noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic HBV infection patients with alanine aminotransferase ≤40 U/L / 临床肝胆病杂志

Objective To investigate the noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic hepatitis B virus (HBV) infection patients with alanine aminotransferase (ALT) ≤40 U/L under the guidance of liver pathology. MethodsA retrospective analysis was performed for the clinical data of 377 HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L who were hospitalized in Affiliated Hospital of Yan’an University, from October 2013 to August 2018 and underwent liver biopsy, among whom the patients with inflammatory activity ＜A2 and fibrosis stage ＜F2 were enrolled as non-antiviral therapy group(n=266), and the patients with inflammatory activity ≥A2 or fibrosis stage ≥F2 were enrolled as antiviral therapy group(n=111). The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; univariate and multivariate binary logistic regression analyses were used to screen out the influencing factors for the initiation of antiviral therapy; the receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of each indicator in determining the need for antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L. ResultsOf all 377 patients, 266 (70.6%) did not need antiviral therapy for the time being, and 111 (29.4%) had marked liver damage and thus needed active antiviral therapy. The multivariate analysis showed that liver stiffness measurement (LSM) (odds ratio ［HR］=2.003, 95% confidence interval ［CI］: 1.647-2.437, P＜005), HBsAg (HR=1.563, 95% CI: 1.110-2.200, P＜0.05), HBV DNA (HR=1.519, 95% CI: 1173-1.966, P＜0.05), and albumin (HR=0.939, 95% CI: 0.884-0.998, P＜0.05) were independent influencing factors for the initiation of antiviral therapy. The ROC curve analysis showed that the area under the ROC curve (AUC) was 0.749 (95% CI: 0.699-0799) for LSM, 0642 (95% CI: 0.586-0.699) for HBV DNA, and 0.565 (95% CI: 0.507-0.623) for HBsAg, and the combination of LSM, HBV DNA, and HBsAg had a larger AUC of 0.779 (95% CI: 0.732-0.827). ConclusionThe levels of LSM, HBV DNA, and HBsAg have a reference value in determining the initiation of antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT≤40 U/L.

Expression of HBcAg in hepatocytes and its association with the efficacy of antiviral therapy / 临床肝胆病杂志

ObjectiveTo investigate the effect of the expression of HBcAg in hepatocytes on the serum level of HBcAb and seroconversion of HBeAg after antiviral therapy with nucleos(t)ide analogues (NUCs). MethodsSerum samples and liver tissue paraffin sections were collected from 101 chronic hepatitis B (CHB) patients who received antiviral therapy with NUCs in Nanfang Hospital and Panyu Central Hospital from January 2015 to June 2018. ELISA was used to measure the serum level of HBcAb, and immunohistochemistry was used to measure the expression of HBcAg in the liver. The GEO database (GSE96851) was analyzed to obtain differentially expressed genes in the liver of patients with HBcAg-positive hepatitis. The two-independent-samples t test was used for comparison of continuous data between two groups; the multiple-independent-samples nonparametric Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and Dunnett method was used for further comparisons; the chi-square test was used for comparison of categorical data between groups. ResultsThe expression pattern of HBcAg in hepatocytes was classified as absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression, and according to expression level, HBcAg expression was classified as grades Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression. HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 16.67%, 22.73%, and 24.24%, respectively, in the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression (χ2=4753, P=0.037), and HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 13.04%, 27.59%, and 26.67%, respectively, in the patients with grade Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression (χ2=6.580, P=0.016). There were significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression of HBcAg (HBcAb-IgM: H=9.760, P=0.021; total HBcAb: H=21.46, P＜0.001), and there were also significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with grade Ⅰ, Ⅱ, Ⅲ, and IV expression of HBcAg (HBcAb-IgM: H=18.80, P＜0.001; total HBcAb: H=26.03, P＜0.001). The analysis of differentially expressed genes in the liver showed that the expression of antibody-related genes was upregulated in the liver of patients with HBcAg-positive acute liver failure. ConclusionThe expression pattern and level of HBcAg in the cytoplasm of hepatocytes are associated with serum HBcAb, and the measurement of HBcAg may help to predict the efficacy of antiviral therapy with NUCs.

Research advances in predictive markers for HBeAg seroconversion in chronic hepatitis B patients treated with nucleos(t)ide analogues / 临床肝胆病杂志

Nucleos(t)ide analogues (NAs) are effective inhibitors for HBV replication and have become the preferred antiviral regimen for most patients with chronic hepatitis B (CHB). HBeAg seroconversion is an important index used to evaluate the durability and efficacy of antiviral therapy in HBeAg-positive CHB patients. The search for biomarkers that can predict HBeAg clearance or seroconversion after NAs treatment plays an important role in the selection of antiviral drugs, the adjustment of treatment regimens, and the achievement of individualized treatment. This article reviews the value of related markers, including HBV DNA, HBV RNA, anti-HBc, and HBcrAg, in predicting HBeAg clearance or seroconversion in CHB patients treated with NAs.

Advances in the diagnosis and treatment of HBeAg-negative chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B (CHB) is one of the most common chronic infectious diseases in China, and the prevalence rate of HBeAg-negative CHB has been increasing year by year, causing serious harm to the security of public health in China. With reference to the pathogenesis, diagnosis, and treatment of HBeAg-negative CHB, this article reviews the clinical research advances in recent years and summarizes the new advances in the diagnosis and treatment of HBeAg-negative CHB.

Value of serum HBV RNA in HBeAg-negative patients with chronic hepatitis B / 中华肝脏病杂志

Objective@#To analyze serum HBV-RNA levels in patients with chronic hepatitis B whose serum HBV-DNA has dropped to undetected levels after treatment with entecavir, and to explore the correlation between HBV-RNA level and liver biochemical parameters, which lay the research foundation for the clinical significance of new serological marker HBV-RNA.@*Methods@#HBeAg negatively detected 107 cases with chronic hepatitis B whose serum HBV-DNA test results were lower than detection level for six consecutive months after receiving standard nucleoside therapy for more than 12 months were included. HBV-RNA level was detected by Perkin-Elmer reagent. HBV-DNA level was detected by Roche Cobas. Hitachi automatic biochemical analyzer was used to detect ALT and AST. Architect chemiluminescence analyzer was used to detect HBsAg, HBeAg, anti-HBe and anti-HBc. RStudio software was performed to analyze the correlation between HBV-RNA level and liver biochemical parameters. Logistic regression was used to analyze the independent factors influencing HBV-RNA level.@*Results@#The positive detection rate of serum HBV-RNA in patients with chronic hepatitis B whose serum HBV-DNA had dropped to undetected levels after ETV treatment was 22.43%. HBsAg, ALT and AST levels in HBV-RNA positive group were slightly higher than HBV-RNA negative group, while anti-HBc levels were slightly higher in HBV-RNA negative group. There was no difference in the level of anti-HBe between the HBV-RNA negative and the positive group. Logistic regression analysis showed that anti-HBc was an independent factor influencing the level of HBV-RNA detection (P = 0.021).@*Conclusion@#HBV-RNA can be detected in some patients with chronic hepatitis B whose serum HBV-DNA level has dropped to undetected levels after ETV treatment. Serum HBV-RNA only comes from the direct transcription of cccDNA, so it is better than HBV-DNA and HBsAg to reflect cccDNA level or activity. Anti-HBc, as an independent factor influencing the level of HBV-RNA, may be used in combination as a new marker to predict the efficacy of antiviral therapy.

Comparison of the effect of tenofovir disoproxil fumarate and entecavir in the treatment of chronic hepatitis B with positive E antigen / 中国基层医药

Objective To compare the efficacy and safety of tenofovir disoproxil fumarate ( TDF) and entecavir(ETV) in the treatment of chronic hepatitis B(CHB) with positive hepatitis B E antigen(HBeAg). Methods A total of 104 cases with newly diagnosed HBeAg positive CHB were selected and randomly divided into TDF group and ETV group,with 52 cases in each group. The TDF group was given 300mg/d TDF,and the ETV group was given 0. 5mg/d ETV. All the patients were continuously treated for 12 months. The serum HBV DNA, HBeAg and ALT levels before and after treatment were compared between the two groups. Results Before treatment,there were no statistically significant differences in serum HBV DNA,HBeAg and ALT levels between the two groups ( t=0. 12, 1. 51,1. 62,all P＞0. 05). The serum HBV DNA,HBeAg and ALT levels in the two groups were decreased after treatment,and the decrease of serum HBV DNA level in the TDF group was more significant than that in the ETV group,the difference was statistically significant(t =3. 54,P ＜0. 05),but there were no statistically significant differences in serum HBeAg and ALT levels between the two groups(t=0. 04,0. 79,all P＞0. 05). The total effective rate of the TDF group was 92. 31% (48/52),which was significantly higher than 76. 92% (40/52) in the ETV group (χ2=4. 73,P＜0. 05). During treatment,the incidence rate of adverse reaction of the TDF group was 7. 69% (4/52),which was lower than 11. 54% (6/52) of the ETV group,but the difference was not statistically significant (χ2=0. 44,P＞0. 05). Conclusion TDF has better clinical effect in treating newly diagnosed HBeAg positive CHB than ETV due to TDF can inhibit HBV DNA replication significantly,but the safety of TDF and ETV is similar.

Clinical safety of short-term antivirus intervention in 54 pregnant women with high viral load of hepatitis B e antigen and the effect of blocking mother-to-child transmission of hepatitis B virus / 中国医师进修杂志

Objective To investigate the effects and safety of short-term telbivudine intervention on blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with hepatitis B e antigens (HBeAg) positive during mid-gestation. Methods Fifty-four chronic HBV infection pregnant women with HBeAg positive from November 2016 to November 2017 in Dalian Sixth People′s Hospital Affiliated to Dalian Medical University were selected, and the serum HBV DNA (logarithmic transformation) of pregnant women was ≥1010 U/L. The pregnant women began oral telbivudine 600 mg at the 24th week of pregnancy, 1 time/d, and stopped at the day of delivery. The neonates were injected 10 μg hepatitis B vaccine and 100 U HBV immunoglobin 12 h after parturition, and they were injected 10 μg hepatitis B vaccine at 1 and 6 months of birth. The HBV DNA, creatine kinase (CK), alanine aminotransferase (ALT) and total bilirubin (TBIL) at 12th, 24th, 28th, 32th week of pregnancy and 1, 7 months after parturition were detected. The hepatitis B surface antibody (HBsAb) and hepatitis B surface antigen (HBsAg) of infants during 28 to 32 weeks of birth were detected. Results There were no statistical differences in CK, ALT and TBIL of 54 pregnant women (P＞0.05). The HBV DNA at 28th, 32th week of pregnancy and 1 month after parturition was significantly lower than that at 12th week of pregnancy (5.7 ± 2.2, 5.1 ± 2.3 and 8.3 ± 1.7 vs. 9.5 ± 1.0), and there was statistical difference (P＜0.05); there was no statistical difference between 7 months and 12th week of pregnancy after parturition (P＞0.05). During 28 to 30 weeks of birth, all the neonates showed serum HBsAb>109 U/L and HBsAg < 30 U/L. Conclusions Short-term intervention with telbivudine in mid-gestation for pregnant women infected with HBV could significantly reduce the level of serum HBV-DNA to the safety level or below. The adverse effects are not found during the telbivudine intervention period. Of note, after drug withdrawal, the HBV DNA level will rebound variously. The virus related detection conducted on the neonates indicates that short-term telbivudine intervention can realize complete MTCT blocking.

Value of liver stiffness measurement in the diagnosis of liver fibrosis degree in HBeAg-positive patients with chronic HBV infection / 临床肝胆病杂志

To investigate the value of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis degree in HBeAg-positive patients with chronic HBV infection. Methods A retrospective analysis was performed for the clinical data of 330 HBeAg-positive patients with chronic HBV infection who were hospitalized in Affiliated Hospital of Yan’an University from October 2013 to August 2018 and underwent liver biopsy, and according to liver pathological results, these patients were divided into mild liver fibrosis group (F0-F1) and significant liver fibrosis group (F2-F4). The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate analyses were performed to screen out the indices for the diagnosis of significant liver fibrosis, and the receiver operating characteristic (ROC) curve was plotted for these indices to evaluate their value in the diagnosis of significant liver fibrosis. Results Of all 330 patients, 245 had mild liver fibrosis and 85 had significant liver fibrosis. There were significant differences between the two groups in HBV DNA, HBsAg, HBeAg, HBcAb, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and LSM (all P＜0.05). The multivariate analysis showed that HBsAg and LSM were independent risk factors for significant liver fibrosis (both P＜0.05). The ROC curve analysis showed that only LSM had a diagnostic value, with an area under the ROC curve of 0.744 (95% confidence interval: 0.680-0.808). At the optimal cut-off value of 6.15 kPa, LSM had a sensitivity of 62.4%, a specificity of 76.3%, an accuracy of 72.1%, a positive predictive value of 72.5%, and a negative predictive value of 67.0% in predicting significant liver fibrosis. ConclusionLSM has a good value in predicting significant liver fibrosis in HBeAg-positive patients with chronic HBV infection.

Association between HBeAg-negative chronic hepatitis B and preC/BCP mutation / 临床肝胆病杂志

Studies on the HBV gene have shown that HBeAg-negative chronic hepatitis B (CHB) is associated with gene mutations in the pre-C (preC) and basic core promoter (BCP) region of HBV DNA, and it is pointed out that the mutation in the preC/BCP region can affect the expression of serum HBeAg and is closely associated with the low replication of HBV DNA in the body, the progression of diseases, and the response to antiviral therapy, which makes the treatment of CHB more complicated. This article reviews the current status of the treatment of HBeAg-negative CHB, structure and mutation of HBV preC/BCP region, and the influence of mutation on the progression of HBeAg-negative CHB and the effect of antiviral therapy for hepatitis B.

Correlation of HBV genotyping and drug resistance mutation in Hohhot,Inner Mongolia / 中国基层医药

Objective To investigate the relationship between HBV -DNA load and serum markers in chronic hepatitis B( CHB) patients in Hohhot,Inner Mongolia,and to explore the mutation of HBV genotype and nucleoside analogue.Methods From January 2015 to December 2017,one hundred and ninety-three CHB patients hospitalized in the People＇s Hospital of Inner Mongolia were selected randomly.The clinical diagnostic criteria for all admitted patients were based on the " Guidelines for the Prevention and Treatment of Chronic Hepatitis B" jointly formulated by the Infectious Diseases Society of 2010. The HBV -DNA load of HBV was detected by real -time quantitative PCR,and the correlation between HBV -DNA load and serum markers was analyzed. Seventy -nine patients were selected from 193 hospitalized patients,PCR-reverse dot blot hybridization was used to analyze HBV genotyping and the drug resistance mutations of different genotypes.Results The differences of HBeAb level and HBV-DNA load between HBeAg positive patients and negative patients were statistically significant(all P<0.001). Of 79 serum specimens of HBV infected people,9 cases(11.4% ) were B genotypes,and 70 cases of C genotype (88.6% ).Of them,25 cases had different loci variation,the rate of variation was 31.6% (25/79),with the unit point rtS213T mutation dominated,accounting for about 24.0% (6/25).Conclusion In Hohhot Inner Mongolia patients with CHB,HBV-DNA load with HBeAg and HBe Ab level are correlated;genotype in patients including B type and C type,which is mainly genotype C;patients with CHB mainly had drug resistance to lamivudine and adefovir dipivoxil, mutations including rtS213T,and hybrid mutation.

Low-levels of HBsAg quantification at 48-week in HBeAg-negative chronic hepatitis B patients are the advantageous population for HBsAg clearance / 中华肝脏病杂志

Objective@#To analyze the therapeutic effect on HBeAg-negative chronic hepatitis B patients treated with Peg-IFNα-2a combined with NAs to obtain the influencing factors for predicting HBsAg clearance.@*Methods@#A retrospective study was conducted to investigate the effect of pegylated interferon alpha-2a combined with nucleoside analogues (lamivudine/adefovir dipivoxil) on HBeAg-negative chronic hepatitis B. The treatment course was 96 weeks. Patients were followed up 120 weeks after the treatment. HBsAg clearance at 120 weeks was taken as the objective of the study. Logistic regression and receiver operating characteristic curve analysis screened the related factors affecting HBsAg clearance. χ 2 test was used to compare count data.@*Results@#111 patients were treated with pegylated interferon alpha-2a combined with nucleoside analogues, and 107 patients completed the scheduled course of treatment and follow-up. HBsAg clearance rate at120 week was 29.0% (31/107). The influencing factors for analysis were: (1) gender had no effect on HBsAg clearance rate; age and baseline levels of HBV DNA and alanine aminotransferase had no significant effect on HBsAg clearance; low baseline level of HBsAg (< 3.023 lgIU/ml) was beneficial to HBsAg clearance. The area under the working characteristic curve of the subjects was 0.746, the positive predictive value was 44.4%, and the negative predictive value was 86.8%. (2) HBsAg quantification or decline in 24 weeks and 48 weeks of treatment had a good predictive effect on HBsAg clearance, and the 48 weeks predicted value was higher than 24 weeks. When the HBsAg quantification was≤2.070 lgIU/ml at 48 weeks, the area under the receiver operating characteristic curve was 0.931, the positive predictive value was 52.8%, and the negative predictive value was 94.4%. When HBsAg decreased from baseline to≥0.991 lgIU/ml, the area under the receiver operating characteristic curve was 0.888, the positive predictive value was 50.8%, and the negative predictive value was 97.9%. (3) The analysis of HBsAg subgroup levels at 48 weeks suggested that the "interval analysis" can forecast HBsAg clearance more exactly than "nodal analysis" .The final HBsAg clearance rate of 100 IU/ml < HBsAg≤1 000 IU/ml, 10 IU/ml < HBsAg≤100 IU/ml and HBsAg≤10 IU/ml groups reached 6.7%, 31.8% and 67.7%, respectively. (4) The ALT abnormal group in the course of treatment obtained a higher HBsAg clearance rate (48.0%, 12/25).@*Conclusion@#96-weeks long-term treatment with pegylated interferon-alpha -alpha-2a combined with nucleoside analogues for HBeAg-negative chronic hepatitis B has a good predictive value for HBsAg clearance at baseline and during treatment. The "interval level" of HBsAg at 48-weeks is more accurate in predicting HBsAg clearance, suggesting that HBeAg-negative chronic hepatitis B patients with low HBsAg levels at 48-weeks are the advantageous populations with HBsAg clearance. These patients are worthy of prolonged treatment to pursue "clinical cure".

Liver histological changes in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection with low hepatitis B virus load / 中华传染病杂志

Objective To determine the predictive factors for antiviral therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection [HBeAg(-) CHBI] patients with HBV DNA＜4.3 lg IU/mL.Methods A total of 179 HBeAg (-) CHBI patients were retrospective analyzed.Histology activity index (HAI) and fibrosis (S) were scored according to the Knodell HAI scoring system,and HAI＞3 and/or S≥3 was adopted as indications for treatment.Univariate and multiple regression analysis were used to assess factors associated with treatment indications.Receiver operating curves (ROC) and area under curve (AUC) were used to determine the predictive value of relevant factors.Results There were 81 cases with HAI＞3 (45.3％) and 72 with S≥3 (40.22％),and the proportion of patients with indications for treatment was 54.7 ％.Multiple regression analysis showed that age,γ-glutamyl transpeptadase (γ-GT),platelet (PLT) and albumin (Alb) were the predictive factors for the severity of liver damage and indication for treatment (all P＜0.05).The AUC for age,PLT,γ-GT and Alb were 0.655,0.657,0.726 and 0.65,respectively,and the corresponding Yoden index for age,PLT,γ-GT,and Alb were 0.297,0.426,0.03 and 0.012,respectively,the sensitivities of predicting HBeAg (-CHBI for treatment indications were 0.643,0.842,0.705 and 0.653,respectively.Conclusions This study shows that 54.7％ of HBeAg(-)CHBI patients with HBV DNA＜4.3 lg IU/ml have significant liver histological changes and require antiviral treatment.Older age,higher γ-GT,lower PLT and lower Alb levels are the predictive factors for treatment.

Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases

BACKGROUND/AIMS: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. METHODS: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ≥7.9 kPa. RESULTS: A total of 214 patients were included in the analysis, and 62% of them had a BMI ≥25 kg/m². During follow-up, 4% of patients showed transaminase elevation ( < 1.5 times normal). Most patients had a viral DNA level < 2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P < 0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ≥25 kg/m² versus 56% of patients without SF (P < 0.05). CONCLUSIONS: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission / 中华流行病学杂志

Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in newborns,as well as how they would influence the increasing risk on HBV intrauterine transmission.Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan.Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates.The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM).Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (0R=4.08,95％ CI:1.89-8.82).Rates of T.reg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29,P=0.022).Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers.Frequencies of both Treg and HBeAg in newboms and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant (x2=18.73,P＜0.001;x2=181.60,P＜0.001;x2=183.09,P＜0.001).Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,mother's HBeAg titers were positively related to the percentage of Treg in their newboms (rs=0.19,P=0.039).In addition,the frequencies of Treg were negatively correlated with pDC and CD4 + T cell in their newborns (rs=-0.21,P=0.017;r,=-0.23,P=0.009).Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.