Hepatitis B Surface Antigen Status Research Articles

The Association Between Weight Loss and Hepatitis B Surface Antigen Seroclearence in Chronic Hepatitis B Patients

Background: In chronic hepatitis B (CHB) patients, hepatitis B surface antigen (HBsAg) seroclearance is the main target of therapy and is rarely observed. Objectives: This study aimed to investigate the factors affecting HBsAg loss by focusing especially on the relationship between weight loss and HBsAg loss. Methods: This study was designed retrospectively to assess HBsAg status and clinical and laboratory findings in CHB patients, as well as cross-sectionally to evaluate lifestyle factors. A total of 5600 hepatitis B (HB) infection patients who were treated or followed between 2008 and 2020 were evaluated retrospectively. In the HBsAg loss group, 94 CHB patients were examined based on exclusion criteria, and 95 patients without HBsAg loss were matched as controls. Patient data and laboratory findings were retrieved from patient files. All participants were surveyed using a questionnaire developed by the authors, which inquired about the lifestyle characteristics of CHB patients. The questionnaire covered topics such as the use of herbal products, coffee consumption, medication history, antiviral treatment, concurrent diseases, weight changes, and patient demographics. Statistical analysis was performed using SPSS version 25.0. The Student's t-test was used to compare quantitative variables, while the chi-square test was used for categorical variables. A paired samples t-test was used to compare dependent samples. The statistical significance level was set at a p value less than 0.05. Results: The basal mean hepatitis B virus (HBV) DNA level was significantly lower in the HBsAg loss group (P < 0.001). The prevalence of hyperlipidemia comorbidity (P = 0.008) and moderate/severe hepatosteatosis (P < 0.05) was significantly higher in the HBsAg loss group compared to the non-HBsAg loss group. Prior to HBsAg loss, 44 (47%) patients in the HBsAg loss group experienced weight loss, whereas only 22 (23%) patients in the non-HBsAg group had a history of weight loss (P < 0.001). Conversely, the incidence of weight gain was significantly lower in the HBsAg loss group (P = 0.001). A paired samples t-test was conducted to compare the baseline and last period body mass index (BMI) means of the HBsAg loss group, revealing a statistically significant decrease in mean BMI in the last period (P < 0.001). Conclusions: Weight loss was significantly associated with HBsAg seroclearance in patients with CHB infection. Conversely, weight gain was associated with HBsAg persistence.

Prediction Model for the Clearance of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B before Interferon Therapy: A Prospective Case-Control Study.

To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500 000 Chinese Adults.

Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16-1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16-1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06-1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92-1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57-1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89-1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90-1.48), suggesting possible mediation by abnormal liver function. Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.

High prevalence of hepatitis delta virus among people with hepatitis B virus and HIV coinfection in Botswana

BackgroundApproximately 15–20 million people worldwide are infected with hepatitis delta virus (HDV), which is approximately 5 % of people with chronic hepatitis B virus (HBV). Sub-Saharan Africa has high HDV prevalence, leading to worse clinical outcomes among people who are HIV/HBV/HDV tri-infected. There are limited data on HDV prevalence among people with HIV (PWH) who are HBV-infected and uninfected in Botswana. We, therefore, determined HDV prevalence among PWH in Botswana. MethodsThis was a retrospective cross-sectional study utilizing archived plasma samples from PWH with results for HBV markers such as hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) and hepatitis B e antigen (HBeAg). Samples were categorized according to their HBsAg status and screened for anti-HDV antibodies. Total nucleic acid was extracted from samples with a single positive anti-HDV result, and HDV ribonucleic acid (RNA) load was quantified using the Altona Diagnostic RealStar® HDV RT-PCR kit. Statistical analysis was performed using STATA version 14.0 where p-values < 0.05 were considered statistically significant. ResultsThe study cohort (n = 478) included both HBsAg positive (44 %) and negative (56 %) participants, with a median age of 42 [IQR; 41–43]. Anti-HDV prevalence of (15/211) [7.1 %, 95 % CI: 4.4 – 11.4] was recorded among HBsAg positive participants, all of whom were IgM anti-HBc negative, while 5/6 participants were HBeAg negative. HDV RNA load was detected in 11/12 (92 %) anti-HDV-positive participants. No HDV prevalence was recorded among participants who were HBsAg negative, therefore, the overall HDV prevalence was (15/478) [3.1 %, 95 % CI: 1.9 – 5.1]. HIV viral load suppression was statistically insignificant, irrespective of HDV status. ConclusionsWe report high HDV prevalence among HBsAg-positive PWH in Botswana. Most HDV-positive participants had active HDV infection, therefore, we recommend HDV screening in this cohort to guide their clinical care.

Study on liver histopathology of chronic HBV infected patients with different normal ALT values.

Comparison of liver histopathological findings to explore the occurrence of liver inflammation in patients with chronic hepatitis B (CHB) under different alanine aminotransferase (ALT) normal values. The patients who were diagnosed as chronic hepatitis B virus (HBV) infection by liver histopathology at the Department of Pathology, Beijing Ditan Hospital due to clinical difficulty in defining the degree of liver inflammation or fibrosis were retrospectively enrolled from May 2008 to November 2020. Study of the incidence of significant hepatic histopathology in enrolled patients according to different ALT normal values. Using logistic regression to investigate the relevant factors of significant hepatic histopathology. A total of 1474 patients were enrolled, 56.20% of the patients were male, and the overall patients' age was 36.80 ± 10.60 years. 39.00% of patients had liver inflammation grade G > 1, 34.70% liver fibrosis stage S > 1, and 48.17% patients had significant hepatic histopathology (G > 1 and/or S > 1). Among patients with normal ALT values, 36.40% and 40.40% had significant hepatic histopathology by American Association for the Study of Liver Diseases (AASLD) criteria and Chinese guideline criteria, respectively, but the difference was not statistically significant (χ2 = 3.38, P =0.066). In contrast, among patients with abnormal ALT values, 58.90% and 62.20% of patients had significant hepatic histopathology by AASLD criteria and Chinese guideline criteria, respectively, with no significant difference (χ2 = 2.28, P =0.131). ALT (P <0.001, OR=1.019), hepatitis B surface antigen (HBsAg) (P <0.001, OR=0.665) and hepatitis B e antigen (HBeAg) status (P <0.001, OR=2.238) were relevant factors in the occurrence of significant hepatic histopathology. ALT was positively corelated with grade of inflammation G (r =0.194, P <0.001) and negatively correlated with liver fibrosis stage S (r =-0.066, P =0.021). Our study found no statistically significant differences in the presence of significant hepatic histopathology under the two ALT criteria. ALT, HBsAg and HBeAg status were related to the occurrence of significant hepatic histopathology.

Impact of hepatitis B surface antigen positive grafts on liver transplantation in patients with benign and malignant liver disease

Hepatitis B surface antigen (HBsAg) persists after liver transplantation in almost all patients receiving HBsAg-positive grafts. Chronic hepatitis B virus (HBV) infection is one of the main causes of hepatocellular carcinoma (HCC). We aimed to investigate possible interactions between HBsAg-positive donors, HCC, HBV-related transplant indication, and long-term outcomes. This retrospective study enrolled 1176 patients from two centers between January 2015 and May 2019, of which 135 (11.5%) were HBsAg-positive and 1041 (88.5%) were HBsAg-negative donors. Cox regression models were fitted to study the association between variables and patient and graft survival. In univariate and multivariate analyses, the donor HBsAg status was not significantly associated with patient and graft survival in the entire cohort, but there was a significant interaction between HBsAg-positive donors and HCC, independent of HBV-related transplant indication. The cumulative incidence of patient and graft survival was significantly lower in the subgroup of HCC recipients receiving HBsAg-positive grafts, but no significant difference was found in recipients with benign liver disease. In a subgroup analysis of HCC recipients, HBsAg-positive donors were significantly associated with an increased risk of HCC recurrence (hazard ratio: 1.73; 95% confidence interval: 1.20-2.48; p = 0.003) and similar results were obtained after propensity score matching analysis. We showed excellent outcomes of using HBsAg-positive grafts in patients with benign liver disease, regardless of HBV-related transplant indications. However, positive grafts should be used with caution in recipients with HCC, which are associated with an increased risk of HCC recurrence.

Incidence and Influencing Factors of New Hepatitis B Infections and Spontaneous Clearance: A Large-Scale, Community-Based Study in China.

Background: Hepatitis B surface antigen (HBsAg) is widely used in hepatitis B screening, and HBsAg seroclearance indicates hepatitis B eradication. Few studies have explored the incidence of and determinants for spontaneous seroclearance using a long-term follow-up cohort study. Our research aimed to examine the incidence of and influencing factors for hepatitis B virus infection and spontaneous clearance of HBsAg from a large-scale cohort in China.Methods: A total of 151,926 resident individuals in Tongxiang underwent HBsAg screening at least thrice in a 7-year period. Serum samples collected at baseline and follow-up examinations were tested for HBsAg. Cox proportional hazard models were used to analyze determinants of HBsAg seroclearance and persistent HBsAg presence.Results: Among the 151,926 participants, new hepatitis B infections occurred in 4,497 participants, yielding an incidence rate of 571.38 per 100,000 person-years. The incidence rate for males was higher than that for females. In the multivariate Cox regression analysis, female gender, alcohol drinking history, hepatitis family history and middle-age group were predictors for persistent positive HBsAg status.Conclusions: The incidence rate of new hepatitis B infections was 571.38 per 100,000 person-years. Male and aged people in this community cohort have a higher infection rate. Alcohol drinking and hepatitis family history were risk factor leading to chronic infection. Female and middle-aged people were prone to persistent positive HBsAg status.

Evaluation of a universal hepatitis B vaccination program and antenatal screening for hepatitis B surface antigen: Results from a real-world study 2015–2016

Background and AimsUniversal vaccination against hepatitis B virus (HBV) in infancy was implemented in Israel in 1992. This population-based study aimed to evaluate the coverage rate and cost-benefit of the HBV vaccination program among infants in Israel and the Hepatitis B surface antigen (HBsAg) status in their mothers. MethodsUsing the database of a health maintenance organization with 2 million members, we retrospectively identified, all the infants born in 2015–2016 and their mothers. Maternal data collected included age, ethnicity, country of birth and HBsAg status during pregnancy. HBV vaccination coverage among infants was calculated. A cost-benefit analysis of the HBV vaccination program was conducted based on the actual costs of HBV infection treatments in all HBsAg positive mothers. ResultsOur cohort included 72,792 mothers who gave birth to 77,572 live infants. A total of 71,107 (97.7%) mothers were screened for HBV during pregnancy, of them 124 (0.2%), who gave birth to 132 infants were HBsAg positive. HBV vaccination coverage rates were 94%, 93% and 89%, for the first, second and third dose, respectively. Birth dose coverage of 95% among infants born to HBsAg positive mothers was significantly higher compared to HBsAg negative or unscreened mothers (p < 0.001). The percentage of HBsAg positivity among mothers who were born in Israel, the Former Soviet Union or Ethiopia, were 0.1%, 0.8% and 5%, respectively (p < 0.001). Ethnic differences were not found between HBsAg positive and HBsAg negative mothers. Calculated benefit-to-cost ratios were 1.24:1 and 4.15:1, with and without antenatal HBsAg screening, respectively. ConclusionsThe Israeli vaccination program against HBV infection is epidemiologically and economically justified. High coverage rates among infants born to HBsAg positive mothers reflect very good adherence to the vaccination program and antenatal screening. Higher HBsAg positivity rates among immigrant mothers identify a high-risk population for HBV infection.

Persistent HBV replication and serological response during up to 15 years of tenofovir-based antiretroviral therapy in HIV/HBV-coinfected patients: a multicentre prospective cohort study.

To determine the extent of hepatitis B virus (HBV) suppression and its association with seroclearance of hepatitis 'e' antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HIV/HBV-coinfected patients undergoing long-term tenofovir-based antiretroviral therapy (ART). We prospectively followed 165 HIV/HBV-coinfected patients undergoing tenofovir-based ART. Serum HBV-DNA viral loads and HBeAg and HBsAg status were obtained at tenofovir initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an Exact binomial test. During a median 8.1 years (IQR = 4.0-13.2) of tenofovir treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up = 608 IU/mL, range = 67-52 400 000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during tenofovir treatment: 15.1% (n = 14/93) at 5 years, 3.2% (n = 2/62) at 10 years and, 3.2% (n = 1/31) at 15 years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, P = 0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, P = 0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (P < 0.001). During long-term tenofovir-based ART for HIV/HBV coinfection, persistent HBV viraemia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.

High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus.

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.

Cross-sectional association between long working hours and liver function: the Kangbuk Samsung Health Study

ObjectivesAlthough the effects of long working hours on liver function remain unclear, in South Korea, there is a social perception that long working hours are associated with poor liver function....

Prevalence and molecular characterization of hepatitis B virus infection in HIV-infected children in Senegal

Background and aimsSub-Saharan Africa (SSA) is the region with the most patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) worldwide. However, few studies have focused on SSA children who are at a higher risk of developing a chronic infection than adults. Furthermore, children on first-line antiretroviral therapy (ART) including low genetic barrier drugs may develop both HBV and HIV resistance mutations. The aim of this work was to document HIV-HBV co-infection and to characterize the HBV isolates in children in Senegal. MethodsThis is a retrospective study of 613 children infected with HIV on ART or not. Dried blood spot (DBS) specimens were used to detect hepatitis B surface antigen (HBsAg) with a rapid diagnostic test (RDT). Confirmation of HBsAg status and hepatitis B e antigen (HBeAg) detection was performed on an automated platform using the chemiluminescence assay technology. HBV viral DNA was quantified by real-time polymerase chain reaction (PCR) and the preS1/preS2/HBsAg region was genotyped by nested PCR followed by sequencing using the Sanger technique. ResultsThe prevalence of HIV-HBV co-infection was 4.1% (25/613). The median age of co-infected children was 13 years (2 years–16 years) and 40% (10/25) were girls. Almost all 19/20 (95%) were infected with HIV-1 and 79% (19/24) were treated with 3TC-based triple combination ART. The median duration of time on ART was 15 months (3 months–80 months). More than half of the children 53% (9/17) were experiencing HIV virologic failure and 75% (6/8) had at least one HIV-related resistance-associated mutation (RAM). Of the six children with resistance, none of the three administered treatments were effective on HIV. Of the 25 co-infected children, 82% (18/22) were HBeAg-positive, while the median HBV viral load (VL) was 6.20 log10 IU/mL (24/25 patients), and 62,5% (10/16) of the children had a persistent HBV viremia. Combination of ART was the only factor associated with HBV viremia persistence. Amplification was successful in 15 out of 16 patients (rate of 94%), and the ensuing phylogenetic analysis revealed that eight strains (53%) belonged to genotype A and seven (47%) to genotype E. HBV-related 3TC RAMs were uncovered in 20% of these patients (3/15). HBsAg escape mutations were found in 20% of the children (3/15). ConclusionsOur results showed a high level of drug resistance mutations to both HIV and HBV, a significant level of HBsAg escape mutations, HBV DNA persistence and HIV virologic failure in co-infected children in Senegal. The HBV genotypes found were A and E.

Prognostic Value of Hepatitis B Virus Infection in Very Young Patients With Curatively Resected Breast Cancer: Analyses From an Endemic Area in China.

Background: Hepatitis B virus (HBV) infection has been associated with the risk and prognosis of many malignancies. Nevertheless, the association between HBV and the prognosis of breast cancer is unclear. The objectives of this study were to investigate the prognostic role of hepatitis B surface antigen (HBsAg) and to integrate HBsAg to establish nomograms for better prognostic prediction of very young patients with breast cancer.Methods: This analysis was performed retrospectively in a cohort of 1,012 consecutive very young (≤35 at diagnosis) patients who received curative resection for breast cancer. The significance of HBsAg in the prognosis of these patients was investigated. Univariate and multivariate analyses were used to identify independent variables for disease-free survival (DFS) and overall survival (OS). Nomograms were built based on those identified variables.Results: Overall, 140 of the 1,012 patients (13.8%) were seropositive for HBsAg. The median follow-up was 67.9 (95% CI, 64.4–71.4) months for the entire population. The HBsAg-positive cohort had significantly inferior DFS (HR, 1.66; 95% CI, 1.07–2.56; P = 0.021) and OS (HR, 1.75; 95% CI, 1.10–2.79; P = 0.016) as compared with the HBsAg-negative cohort. The rates of 10-year DFS and OS were 77.4 and 73.0% in the HBsAg-positive group and 84.1 and 85.6% in the HBsAg-negative group, respectively. In multivariable analysis, HBsAg status was identified as an independent significant unfavorable prognostic factor for DFS (P = 0.01) and OS (P = 0.04) in very young patients with breast cancer. Nomograms were established and displayed good calibration and acceptable discrimination. The C-index values for DFS and OS were 0.656 (95% CI: 0.620–0.691) and 0.738 (95% CI: 0.697–0.779), respectively. Based on the total prognostic scores (TPS) of the nomograms, 3 different prognosis groups were identified for DFS and OS.Conclusions: HBsAg is an independent unfavorable prognostic factor for DFS and OS in very young patients with curatively resected breast cancer, and nomograms integrating HBsAg provide individual survival prediction to benefit prognosis evaluation and individualized therapy.

Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis

Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes. We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point. We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P= .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics. In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.

Effects of maternal hepatitis B surface antigen positive status on the pregnancy outcomes: A retrospective study in Xiamen, China, 2011-2018.

ObjectiveHepatitis B virus infection is a major social and economic burden in developing countries, especially in China. We aimed to evaluate the effects of hepatitis B surface antigen (HBsAg) positive status on the pregnancy outcomes in the Chinese population.MethodsThis retrospective cohort study was performed using data from the Medical Birth Registry of Xiamen, China, from January 2011 to March 2018. Multivariate logistic regression analysis was used to assess the association between the HBsAg status and pregnancy outcomes.ResultsThis study included 3,789 HBsAg-positive women and 29, 648 non-exposed women. The HBsAg-positive pregnant women were slightly older in age (29.3±4.3 vs. 28.9±4.4, P< 0.001). Additionally, pregnant women with a positive HBsAg status had higher odds of gestational diabetes mellitus (GDM) (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI], 1.03–1.23), and cesarean delivery (aOR, 1.12; 95%CI, 1.03–1.21). The risk of infants being large or small-for-gestational age, having low-birth weight, and of macrosomia, preterm birth, and stillbirth did not differ significantly between the HBsAg-positive and–negative women.ConclusionIn Xiamen, China, the slightly higher risk of GDM and cesarean section in women positive for HBsAg should not be neglected. Further studies should be conducted to evaluate the effects of HBsAg positivity on the pregnancy outcomes in different ethnic populations.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Spontaneous Flares of Chronic Hepatitis B Virus in Hepatitis Be Antigen Negative Carriers Who Subsequently Clear Hepatitis B Surface Antigen.

Acute exacerbations of chronic hepatitis B virus (HBV) infections can occur in HBV-infected, hepatitis e antigen (HBeAg)-negative patients in the absence of recent withdrawal of antiviral or immunosuppressive therapies. Whether these spontaneous "flares" predict subsequent loss of hepatitis B surface antigen (HBsAg) has yet to be determined. To document the percent of patients who experience spontaneous HBV flares and severity of the flares in chronic HBeAg-negative carriers. A retrospective review of an HBV database identified and followed HBeAg-negative patients for biochemical evidence of flares (ALT > 5× normal) and subsequent HBsAg status. Patients that subsequently cleared HBsAg were matched 1:1 with those who remained HBsAg positive. Of 1299 HBeAg-negative patients followed for 10.2 ± 6.1years, 88 (6.8%) developed spontaneous HBV flares. Flares occurred in 14/115 (12.2%) patients who subsequently cleared HBsAg and 4/111 (3.6%) matched patients who remained HBsAg positive (p = 0.025). The severity of flares was similar in the two study cohorts. Following multivariate analyses, only low HBV-DNA levels at baseline identified patients likely to subsequently clear HBsAg. Although more common in patients who subsequently clear HBsAg, spontaneous HBV flares do not predict subsequent HBsAg clearance.

Acute Hepatitis B or Chronic Hepatitis B with Acute Exacerbation: Differentiating Clinical, Biochemical, Immunonological, and Virological Parameters

Background and Aims: Acute hepatitis B virus (HBV) infection and chronic HBV infection presenting as acute illness have differing prognosis. Differentiation between acute viral hepatitis B (AVH-B) and chronic hepatitis B with an acute exacerbation (CHB-AE) is difficult if prior hepatitis B surface antigen (HBsAg) status is unknown. This prospective study was undertaken to screen various factors that could help with this differentiation. Methods: All consecutive patients presenting with AVH-B like illness were enrolled in this study and were evaluated as per predefined study protocol. Patients were divided into AVH-B and CHB-AE groups based on HBsAg status at the end of 6 months. Results: Significant differences in clinical and laboratory parameters were found between AVH-B and CHB-AE. No statistically significant difference in prodromal symptoms and jaundice was seen. Ascites (40%) and hepatic encephalopathy (10%) were seen only in patients with CHB-AE (P = 0.002 and 0.244, respectively). Anti-hepatitis B virus core antigen immunoglobulin M (IgM anti-HBc) levels ≥10.15 signal-cutoff-ratio (S/CO) had positive predictive value (PPV) and negative predictive value (NPV) of 90% for diagnosis of AVH-B. Hepatitis B virus deoxyriboNucleic acid (HBV DNA) levels ≥25032 IU/mLhas 62.5% PPV and 69% NPV for diagnosis of CHB-AE. Alpha-feto protein (AFP) at >22.5 ng/mLmL for diagnosing CHB-AE has PPV and NPV of 83% and 62%, respectively. All six mortalities were seen in CHB-AE group with median survival of 2 months. Conclusions: Differentiation of AVH-B and CHB-AE is important as management and prognosis differ. Low IgM anti-HBc levels ( 22.5 ng/mL) favor CHB-AE over AVH-B.

Stability of hepatitis B viral load during pregnancy and implications for antepartum prophylaxis: A prospective cohort study.

We examined changes in hepatitis B virus (HBV) viral loads (VLs) in pregnancy, their association with hepatitis B e antigen (HBeAg), and the associated infant outcomes. We prospectively followed 132 mothers positive for hepatitis B surface antigen (HBsAg) and their 135 infants from 2011 to 2015 in Vancouver, British Columbia. Outcome measures included association between maternal HBeAg and high (>200,000 IU/mL) or low (≤200,000 IU/mL) HBV VL, changes in HBV VL through pregnancy, infant HBsAg status, and infant completion of the HBV vaccination series. f the 91 participants with an available HBV VL, 13 (14.3%) had an HBV VL of more than 200,000 IU/mL. Of 59 participants with paired HBeAg and HBV VL in pregnancy, 6 had an HBV VL of more than 200,000 IU/mL; of interest, 2 of the 6 (33.3%) were HBeAg-negative. Thirty-eight participants had HBV VL results at both mid-trimester and delivery. For these 38 participants, Wilcoxon signed-ranks test for paired data found that an HBV VL remained stable (p = .58). We observed no perinatal transmissions. However, 20.7% of infants did not have a documented complete HBV vaccination series, 20.0% did not have post-vaccination HBsAg testing completed, and 18% did not have anti-HBs titres measured by age 12 months. Our study demonstrates that HBeAg and HBV VL are not reliably predictive of each other. This supports the improved predictive value of VL measurement in pregnancy to risk stratify pregnant patients to offer antiviral treatment when indicated and further minimize the risk of perinatal transmission.

Associations Between Hepatitis B Virus Infection and Risk of All Cancer Types

Hepatitis B virus (HBV) has been identified as a major risk factor for hepatocellular carcinoma. However, the associations between HBV infection and other cancer types are not well understood. To assess the associations between chronic HBV infection and risk of all cancer types. This population-based study involved 3 cohorts in China. The China Kadoorie Biobank (CKB) prospective cohort study, conducted between June 2004 and July 2008, used a dipstick assay for detection of serum hepatitis B surface antigen (HBsAg) among 496 732 participants to determine the association between HBV infection and risk of all cancer types. Two cohort studies were used to validate the associations by applying more precise serum HBsAg detection assays: the Qidong cohort (37 336 participants enrolled from November 2007 to April 2011) and the Changzhou nested case-control study (17 723 participants enrolled from June 2004 to September 2005). A total of 97 samples of stomach cancer tissues, 10 samples of pancreatic cancer tissues, and 9 samples of lung cancer tissues were included to assess the presence of HBV replication and expression. Statistical analysis was performed from December 2016 to October 2018. Serum HBsAg status in the population-based stage and HBV DNA status, the expression of hepatitis B X protein, and hepatitis B core antibody (anti-HBc) in the tissue-based stage. Incidence of all cancer types during follow-up. In the CKB cohort, the mean (SD) age of the 496 732 participants was 51.5 (10.7) years; 59.0% of the participants were women. After 4.4 million person-years of follow-up, participants who were HBsAg seropositive (n = 15 355) had a higher risk of hepatocellular carcinoma (hazard ratio [HR], 15.77; 95% CI, 14.15-17.57), stomach cancer (HR, 1.41; 95% CI, 1.11-1.80), colorectal cancer (HR, 1.42; 95% CI, 1.12-1.81), oral cancer (HR, 1.58; 95% CI, 1.01-2.49), pancreatic cancer (HR, 1.65; 95% CI, 1.03-2.65), and lymphoma (HR, 2.10; 95% CI, 1.34-3.31) when compared with participants who were HBsAg seronegative (n = 481 377). Because of the limitation of sample size, only associations of HBV infection with hepatocellular carcinoma and stomach cancer were validated in the Qidong cohort (hepatocellular carcinoma: HR, 17.51; 95% CI, 13.86-22.11; stomach cancer: HR, 2.02; 95% CI, 1.24-3.29); the Changzhou nested case-control study validated only an association between HBV infection and stomach cancer (odds ratio, 1.76; 95% CI, 1.04-2.98). Moreover, among 22 participants with stomach cancer from the Qidong cohort who were anti-HBc seropositive, 12 samples (54.5%) of cancer tissues were HBV DNA positive, while among 25 participants with stomach cancer who were anti-HBc seronegative, no HBV DNA was detected. The same negative and positive rate was observed in the validation set from Zhejiang Tumor Hospital (19 of 35 samples [54.3%] were HBV DNA positive). Moreover, among the 8 patients with stomach cancer from the Qidong cohort who were anti-HBc seropositive, anti-HBc and hepatitis B X protein were expressed in all of their stomach cancer tissue samples. The same phenomenon was observed in the patients with pancreatic cancer but not in the patients with lung cancer, which was consistent with the population-based results of the CKB cohort. This study found that HBV infection was also associated with the risk of nonliver cancer, especially digestive system cancers among adults in China.