Negative Hepatitis B E Antigen Research Articles

Favourable Prognosis of Patients With Untreated HBeAg-Negative Chronic Hepatitis B Virus Infection With HBsAg < 100 IU/mL.

Serum hepatitis B surface antigen (HBsAg) < 100 IU/mL has been recently proposed as one of the key criteria of 'partial cure' in patients with chronic hepatitis B virus (HBV) infection. We analysed the clinical prognosis of hepatitis B e antigen (HBeAg)-negative untreated patients with HBsAg < 100 IU/mL and normal alanine aminotransferase (ALT) levels. Five hundred and twenty-one untreated patients with HBeAg negativity, HBsAg < 100 IU/mL and normal ALT levels were included from three hospitals. Spontaneous HBsAg seroclearance, phase transition, liver fibrosis progression and hepatocellular carcinoma (HCC) development were analysed. The median age was 43.0 years, and 62.2% of the patients were male. After a median follow-up of 25.0 months, 52 (10.0%) patients achieved spontaneous HBsAg seroclearance. The annual HBsAg seroclearance rate is 4.2%. Patients with baseline HBsAg ≤ 10 IU/mL (adjusted hazard ratio [aHR] = 3.490, p < 0.001) and male sex (aHR = 1.980, p = 0.041) were more likely to achieve HBsAg seroclearance. Only 4 (0.8%) and 23 (4.8%) patients transitioned to the immune escape phase and HBeAg-negative indeterminate phase, respectively. Baseline serum HBsAg > 10 IU/mL (aHR = 3.846, p = 0.034) and detectable HBV DNA (aHR = 2.672, p = 0.023) were associated with transition to the HBeAg-negative indeterminate phase. No patient developed HCC or had fatal outcomes. HBeAg-negative patients with serum HBsAg < 100 IU/mL and normal ALT levels had a favourable prognosis. HBsAg ≤ 10 IU/mL and male sex were associated with a higher rate of HBsAg seroclearance, while HBsAg > 10 IU/mL and detectable HBV DNA were associated with a higher risk of transition to the indeterminate phase.

Intrauterine Transmission of Hepatitis B Cannot Be Ruled Out by A Single Negative Hepatitis B e Antigen (HBeAg) Result among Hepatitis B Surface Antigen (HBsAg) - Positive Pregnant Women

BACKGROUND: The risk factors for intrauterine transmission of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive pregnant women are poorly understood. Numerous factors are considered to be involved, including placental barrier, obstetric environment, high viral load, and positivity of hepatitis B e antigen (HBeAg). This study was conducted to investigate the role of placenta barrier, clinical, and viral factors in intrauterine transmission of HBV.METHODS: A cross-sectional study was conducted involving 1,353 pregnant women who underwent HBsAg screening. Eighty-four (6.2%) women were detected as HBsAg positive and were examined for HBsAg level, anti-HBs, anti-HBc, HBeAg/hepatitis B e antibody (anti-HBe) status, and HBV DNA presence in cord blood. Quantitative HBV DNA was analyzed using real-time polymerase chain reaction (PCR).RESULTS: Eighty-four of 1,353 subjects were HBsAg-positive. HBV DNA was positive in 28/84 (33.7%) maternal sera, 19/79 (24.05%) placental specimens, and 9/83 (10.84%) in cord blood. There were significant associations between HBV DNA in maternal serum (p=0.000) and placental tissue (p=0.000) with HBV DNA in the cord blood. No clinical factors were associated with HBV DNA transmission in cord blood. Sixty percent of viral load &gt;5.3 log10 copies/mL were found in the cord blood, of which 43.8% HBeAg positive and 3.1% HBeAg negative.CONCLUSION: Reduced transmission via compartments established the placenta’s barrier function in mother-to-child transmission. A high maternal viral load and positive HBeAg were risk factors for intrauterine transmission, while negative HBeAg still has the possibility of transmission.KEYWORDS: mother-to-child transmission, hepatitis B virus, intrauterine

High immunocompetence in chronic hepatitis patients with normal alanine transaminase levels and and negative hepatitis B e-antigen for the progression of liver fibrosis.

This study aimed to investigate the role of immunocompetence in chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) levels and negative hepatitis B e antigen (HBeAg) in the risk assessments of the progression of liver fibrosis. We collected the clinical data of 57 patients with CHB, with normal ALT levels and negative HBeAg from December 2020 to December 2022. With hepatitis B virus (HBV) DNA > 20 IU/mL and ALT ≤ 40 U/L, these patients had never undergone antiviral therapy. The levels of CD4+ , CD4+ CD25+ , CD8+ , and CD4+ CD25+ CD127LOW regulatory T cells (Tregs) in the patients were detected using flow cytometry; the liver stiffness measurement (LSM) values of the patients were detected using Fibroscan. There was a statistically significant difference between the levels of fibrosis-4 (FIB-4) and hepatitis B surface antigen (HBsAg) when the cutoff point was HBsAg ≥ 1500 (p < .001). FIB-4 was negatively correlated with HBsAg (R = -0.291, p = .028) and positively correlated with age (R = 0.787, p < .001). LSM was negatively correlated with Treg but this correlation was not statistically significant (p > .05). Findings based on the analysis using logistic regression were as follows: (i) age was the independent risk factor when FIB-4 was used as the indicator for assessing liver fibrosis; (ii) Treg was the independent risk factor when LSM was used as the indicator for assessing liver fibrosis. When Treg was used to predict liver fibrosis, the cutoff value, diagnostic efficacy, area under the receiver operating characteristic (ROC) curve, and p value of the ROC curve were 6.875, 0.641, 0.84, and .027, respectively. Age and Treg are independent risk factors for progressive liver fibrosis. The cutoff value of Treg > 6.81 indicates the need for timely antiviral treatment and can serve as an indicator for evaluating liver fibrosis.

End-of-treatment anti-HBs levels and HBeAg status identify durability of HBsAg loss after PEG-IFN discontinuation.

Hepatitis B surface antigen (HBsAg) loss, namely, the functional cure, can be achieved through the pegylated interferon (PEG-IFN)-based therapy. However, it is an unignorable fact that a small proportion of patients who achieved functional cure develop HBsAg reversion (HRV) and the related factors are not well described. A total of 112 patients who achieved PEG-IFN-induced HBsAg loss were recruited. HBV biomarkers and biochemical parameters were examined dynamically. HBV RNA levels were assessed in the cross-sectional analysis. The primary endpoint was HRV, defined as the reappearance of HBsAg after PEG-IFN discontinuation. HRV occurred in 17 patients during the follow-up period. Univariable analysis indicated that hepatitis B e antigen (HBeAg) status, different levels of hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) at the end of PEG-IFN treatment (EOT) were significantly associated with the incidence of HRV through using the log-rank test. Additionally, time-dependent receiver operating characteristic (ROC) analysis showed that the anti-HBs was superior to anti-HBc in predictive power for the incidence of HRV during the follow-up period. Multivariable Cox proportional hazard analysis found that anti-HBs ≥1.3 log10IU/L (hazard ratio (HR), 0.148; 95% confidence interval (CI), 0.044-0.502) and HBeAg negativity (HR, 0.183; 95% CI, 0.052-0.639) at EOT were independently associated with lower incidence of HRV. Cross-sectional analysis indicated that the HBV RNA levels were significantly correlated with the HBsAg levels in patients with HRV (r=0.86, p=0.003). EOT HBeAg negativity and anti-HBs ≥1.3 log10IU/L identify the low risk of HRV after PEG-IFN discontinuation.

A cautionary note to hepatitis B e antigen (HBeAg)-negative test results in pregnant women in an area prevalent of HBeAg-negative chronic hepatitis B.

Maternal hepatitis B e Antigen (HBeAg) positivity poses a risk for hepatitis B virus (HBV) mother-to-child transmission (MTCT). In resource-constrained settings, HBeAg testing is recommended as an alternative to HBV DNA testing to establish antiviral prophylaxis eligibility. Nevertheless, the high prevalence of HBeAg-negative chronic hepatitis B (e-CHB) in many countries should not be overlooked. We studied HBV characteristics and explored the potential MTCT risk among HBeAg-negative/HBsAg-positive expectant mothers in an area prevalent of e-CHB. Among 1348 pregnant mothers screened for HBV infection, 81 (6.0%) were HBsAg-positive. These women were examined for HBeAg, HBV DNA, and cord blood HBV DNA. Sixteen (19.8%) of the HBsAg-positive mothers were HBeAg-positive, whereas 65 (80.2%) were HBeAg-negative, including eight inactive carriers (HBsAg <100 IU/ml, HBV DNA ≤ 2000 IU/ml, and ALT < 40 IU/L). Of the remaining 57 HBeAg-negative mothers, ten revealed HBV Basal Core Promoter or Precore mutations, with three having high viremia (HBV DNA > 200 000 IU/mL), which is associated with a high MTCT risk and therefore qualifies them for antiviral prophylaxis. This pilot study provides a cautionary note to the interpretation of negative HBeAg test results when determining eligibility for MTCT antiviral prophylaxis in situations with limited resources and in regions where e-CHB is prevalent.

Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B

Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) constitutes an atypical serological profile in chronic hepatitis B virus infection, and the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) remains unclear. To investigate the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with CHB. Consecutive treatment-naive patients with CHB from 2 medical institutions in China were enrolled between January 10, 2015, and March 31, 2021. Severe liver fibrosis and cirrhosis were identified using the aspartate transaminase (AST) to platelet ratio index (APRI), the fibrosis index based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography. Data were analyzed from August 1, 2021, to April 15, 2022. The primary outcomes were rates of severe liver fibrosis and cirrhosis among patients with vs patients without coexistant HBsAg and anti-HBs. Severe liver fibrosis was defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 or higher, or a liver stiffness measurement of 8 kPa or higher; cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis. Of 6534 enrolled patients, 4033 patients (61.7%) were male, and the median (IQR) age was 41.0 (33.0-52.0) years. A total of 277 patients (4.2%) had coexistent HBsAg and anti-HBs. Patients with vs without anti-HBs were older (median [IQR], 46.0 [33.0-55.5] years vs 41.0 [33.0-52.0] years) and had a higher proportion of hepatitis B e antigen (HBeAg) positivity (123 of 277 patients [44.4%] vs 2115 of 6257 patients [33.8%]; P < .001), higher ALT levels (median [IQR], 45.1 [24.6-119.0] U/L vs 36.7 [22.0-77.0] U/L; P = .001) and AST levels (median [IQR], 35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L; P < .001), and lower platelet counts (median [IQR], 173.0 × 103/μL [129.0-212.5 × 103/μL] vs 185.0 × 103/μL [141.0-224.0 × 103/μL]; P = .004), albumin levels (median [IQR], 4.37 [4.11-4.56] g/dL vs 4.43 [4.17-4.61] g/dL; P = .02), and HBsAg levels (median [IQR], 2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/mL; P < .001). Compared with patients without anti-HBs, those with anti-HBs had higher APRI scores (median [IQR], 0.5 [0.3-1.4] vs 0.4 [0.3-0.9]; P < .001), FIB-4 scores (median [IQR], 1.4 [0.9-2.6] vs 1.1 [0.7-2.1]; P < .001), and liver stiffness values (median [IQR], 7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa; P = .003). Patients with anti-HBs also had higher proportions of severe liver fibrosis (102 of 277 patients [36.8%] vs 1397 of 6207 patients [22.5%]; P < .001) and cirrhosis (87 of 277 patients [31.4%] vs 1194 of 6213 patients [19.2%]; P < .001) compared with patients without anti-HBs. The coexistence of HBsAg and anti-HBs was independently associated with severe liver fibrosis (odds ratio [OR], 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01) in the multivariate analysis. However, the association of coexistent HBsAg and anti-HBs with cirrhosis was only observed in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16). In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity. These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.

Use of Hepatitis B-e Antigen to Identify Pregnant Women With Hepatitis B Virus Infection Who Need Antiviral Therapy for Prevention of Mother-to-child Transmission.

ObjectiveTo evaluate the performance of hepatitis B-e antigen (HBeAg) for identifying pregnant women infected with hepatitis B virus (HBV) who are having a high viral load.MethodsA cross-sectional study was conducted at the tertiary care hospital in Bangkok, Thailand between August 2017 and August 2018. Ninety-six pregnant women having positive hepatitis B-s antigen (HBsAg) results were invited to participate into the study. Clinical data and blood samples were collected and tested for HBeAg and HBV DNA levels. Data were reported as percentage and 95% confidence interval (CI).ResultsHigh viral load was found in 25 women (26.0%, 95% CI: 18.3% to 35.6%) and HBeAg showed positive results in 33 women (34.4%, 95% CI: 25.6% to 44.3%). Among antiviral-naïve women, 24 of 30 cases having positive HBeAg results had high viral load (80.0%, 95% CI: 62.7% to 90.5%) while only 1 of 62 negative HBeAg women had high viral load (1.6%, 95% CI: 0.3% to 8.6%).ConclusionAbout one-fourth of HBV-infected pregnant women were at high risk for mother-to-child transmission (MTCT) of the virus and needed antiviral drugs for reducing MTCT. HBeAg may be used to identify women at high risk for MTCT of HBV in a low-resource setting where HBV DNA level test is not available.

Efficacy of Peginterferon alfa-2b in Nucleoside Analogue Experienced Patients with Negative HBeAg and Low HBsAg: A Non-Randomized Clinical Trial.

IntroductionHepatitis B surface antigen (HBsAg) clearance is the treatment goal for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB). However, its rate is extremely low with nucleoside (acid) analogues (NAs) monotherapy. Peginterferon could enhance HBsAg clearance. This study aimed to evaluate the efficacy of peginterferon alfa-2b (PegIFNα-2b) in NAs-experienced patients with CHB with negative HBeAg and low HBsAg level.MethodsHBeAg-negative patients with CHB who had received NAs therapy over 24 weeks with HBsAg < 1500 IU/mL and HBV DNA < 100 IU/mL were enrolled. Patients received either PegIFNα-2b add-on therapy (n = 108) or continuous NAs monotherapy (n = 75). The primary endpoint was HBsAg clearance rate at week 48.ResultsAt week 48, serum HBV DNA was undetectable among all PegIFNα-2b add-on therapy patients. Almost all patients maintained HBV DNA suppression in the PegIFNα-2b add-on group (100%, 108/108) and NAs monotherapy group (97.33%, 73/75). Only patients with PegIFNα-2b add-on therapy achieved HBsAg clearance (50.93%, 55/108) and HBsAg seroconversion (48.15%, 52/108) at week 48. Patients with baseline HBsAg < 100 IU/mL achieved the highest HBsAg clearance rate and HBsAg seroconversion rate at week 48 (60.87%, 28/46 and 58.70%, 27/46 respectively). HBsAg clearance and HBsAg seroconversion at week 72 had no significant difference with continuing or discontinuing PegIFNα-2b therapy after 48 weeks of treatment. PegIFNα-2b add-on therapy was well tolerated.ConclusionsPegIFNα-2b add-on therapy increases HBsAg clearance rate and seroconversion rate for HBeAg-negative patients with CHB, particularly for those with lower HBsAg level. It would be unnecessary to prolong PegIFNα-2b duration after 48 weeks of PegIFNα-2b treatment.

Prevalence of hepatitis B e antigenemia in Bahraini hepatitis B patients: A retrospective, single-center study.

Background and AimHepatitis B e (HBe) antigen (HBeAg) is commonly encountered among hepatitis B patients and is indicative of active infection. There is a lack of data in the literature about the prevalence of HBeAg among hepatitis B patients in Bahrain and its impact on the disease. The aims of this study were to investigate the prevalence of HBeAg among a sample of hepatitis B patients in Bahrain and to analyze their associated laboratory profile, radiological characteristics, comorbidities, and complications.MethodsThis was a retrospective record‐review study conducted on patients' records at Salmaniya Medical Complex hospital in Bahrain during the period of 2011–2016. All records of hepatitis B patients who had HBeAg tests performed were included in this study.ResultsOf 323 patients recruited, 18.9% had positive HBeAg. The prevalence of anti‐HBe antibodies and hepatitis B core immunoglobulin G (HBc IgG) differed significantly between patients with positive and negative HBeAg (P < 0.001, P = 0.026, respectively). Alanine transferase and gamma‐glutamyl transferase were significantly higher among patients with positive HBeAg (P = 0.017, P = 0.016, respectively). There was no significant difference with regard to the prevalence of hepatitis C virus, human immunodeficiency virus, hepatocellular carcinoma, or liver transplantation between HBe‐positive and ‐negative patients (P ≥ 0.05).ConclusionHBeAg is prevalent among hepatitis B patients in Bahrain and is associated with a significantly different laboratory profile.

Bayesian network to predict hepatitis B surface antigen seroclearance in chronic hepatitis B patients.

There is a need for an interpretable, accurate and interactions-considered model for predicting hepatitis B surface antigen (HBsAg) seroclearance. We aimed to construct a Bayesian network (BN) model using available medical records to predict HBsAg seroclearance in chronic hepatitis B (CHB) patients, and to evaluate the model's performance. This was a case-control study. A total of 1966 consecutive CHB patients (mean age 39.04±11.23years) between January 2006 and June 2015 were included. The demographic and clinical characteristics, laboratory data and imaging parameters were obtained and used to build a BN model to estimate the probability of HBsAg seroclearance. Baseline serum HBsAg and hepatitis Be antigen (HBeAg) levels, virological response and HBeAg seroclearance were the most significant predictors of HBsAg seroclearance. The post-test probability table showed that patients with baseline HBsAg concentrations ≤2000IU/mL, negative baseline HBeAg, an initial virological response and without HBeAg seroclearance (i.e. no recurrence of HBeAg positivity during follow-up) were most likely to have HBsAg seroclearance. The constructed BN model had an area under the receiver operating characteristic curves of 0.896 (95% confidence interval [CI]: 0.892, 0.899), a sensitivity of 0.840 (95% CI: 0.833, 0.846), a specificity of 0.880 (95% CI: 0.876, 0.884) and an accuracy of 0.878 (95% CI: 0.874, 0.882) for predicting HBsAg seroclearance. The established BN model accurately estimated the probability of HBsAg seroclearance and is a promising tool to assist clinical decision-making.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

HBeAg Negativity Is Associated With More Advanced Liver Fibrosis in Patients With Chronic Hepatitis B: A Propensity Score-Matching Analysis.

Serum hepatitis B e antigen (HBeAg) status is associated with the progression of chronic hepatitis B (CHB). The authors aimed to investigate the relationship between HBeAg status and liver pathology in CHB patients. A total of 683 treatment-naive CHB patients who had undergone liver biopsy were retrospectively enrolled from 2 medical centers. Propensity score-matching (PSM) method was performed to adjust the imbalance of baseline confounders between HBeAg-positive and HBeAg-negative CHB patients. HBeAg-negative CHB patients (n=338) exhibited more advanced liver fibrosis than HBeAg-positive CHB patients (n=345) before PSM (P<0.001). However, there were no significant differences in the distribution of inflammation grades between HBeAg-positive and HBeAg-negative CHB patients (P=0.051). Of these 683 CHB patients, 123 patients were included in each group after PSM. HBeAg-negative CHB patients still showed significantly advanced liver fibrosis as compared with HBeAg-positive CHB patients (P=0.03) after PSM. Furthermore, the distribution of liver inflammation grades in the HBeAg-negative CHB patients was also more severe than patients with HBeAg-positive (P=0.037). HBeAg-negative status was identified as an independent risk factor of significant liver fibrosis (P=0.011) by multivariate analysis. HBeAg negativity is associated with more advanced liver fibrosis in CHB patients.

3173 Spontaneous HBsAg Seroclearance in a Patient With Chronic Hepatitis B: Do We Need Surveillance?

INTRODUCTION: Hepatitis B virus (HBV) infection is a global health problem despite an effective vaccination program, routine antenatal screening, and perinatal care. Among the individuals infected with the HBV, about 5 % of adults and 90% of children become chronic carriers. A small percentage of carriers undergo spontaneous seroclearance of Hepatitis B surface antigen (HBsAg). We present a case of spontaneous HBsAg seroclearance in a chronic hepatitis B carrier. CASE DESCRIPTION/METHODS: A 60-year-old Hispanic male with a history of chronic hepatitis B presented to the hepatology clinic for regular follow-up. He was asymptomatic with no stigmata of chronic liver disease. He had been followed in the clinic for nine years. He was HBsAg positive, hepatitis B surface antibody detectable at 6.9 mIU/ml, hepatitis B e antigen (HBeAg) negative, hepatitis B e antibody positive, undetectable HBV DNA levels, and alpha-fetoprotein 17.2 ng/ml. He persistently had normal liver enzymes. Five months after the last positive HBsAg, routine serology showed loss of HBsAg. CT Abdomen with contrast liver protocol showed no evidence of cirrhosis and hepatocellular carcinoma (HCC). The liver biopsy showed no evidence of fibrosis. The patient is on surveillance with a follow-up in 6 months for repeat serology. DISCUSSION: Chronic hepatitis B carriers are at risk of developing decompensated liver cirrhosis and hepatocellular carcinoma. The rate of HBsAg spontaneous seroclearance is estimated to be 1–3% per year. The long-term outcome after HBsAg seroclearance is excellent if there is no pre-existing cirrhosis or viral superinfection. HBsAg carriers who are negative for HBeAg or negative for HBV DNA are more likely to clear HBsAg from serum. AASLD guidelines recommend HCC surveillance in chronic hepatitis B infection, but its usefulness in patients after HBsAg seroclearance without any liver injury remains controversial. Few retrospective studies recommend surveillance in high-risk patients, which include male patients, patients with cirrhosis, HCV superinfection, age ≥50 years at the time of seroclearance and family history of HCC. Surveillance in patients who do not have any risk factors may not be cost effective as the incidence of adverse liver events among them is rare. Our patient had chronic hepatitis B for nine years and underwent spontaneous seroclearance of HBsAg with negative HBeAg and undetectable HBV DNA. He has no evidence of cirrhosis or viral superinfection, thus having a favorable long-term prognosis.

On Treatment Efficacy of Entecavir in Treatment Naïve Chronic Hepatitis B Patients

Background: Worldwide 250 million people are suffering from Hepatitis B Virus (HBV) infection. Treatment with antiviral drugs improve survival and quality of life by preventing disease progression and Hepatocellular Carcinoma (HCC). Indications for antiviral treatment primarily based on serum HBV DNA, Alanine Aminotransaminase (ALT) and severity of liver disease. Entecavir is one of the potent antiviral drug against hepatitis B virus. This study has been conducted to evaluate the efficacy of entecavir in both Hepatitis Be Antigen (HBeAg) positive and HBeAg negative treatment naïve Bangladeshi patients. Materials and methods: A total 205 patients were enrolled in this study from 2010-2014 in outpatients department of Hepatology in Chattogram Medical College Hospital. All patients got Entecavir 0.5 mg daily and followed at 12 weeks, 24 weeks &amp; 52 weeks of the treatment by ALT, HBsAg, HBe- Ag and HBV DNA. 55 patients lost during follow- up and 150 patients completed 52 weeks treatment and finally evaluated. Results: The mean HBV DNA at baseline was 26.4 x 109 ± 7.4 x 109 copies / ml which was decreased to 2.2 x 106 ± 1.4 x 105 copies/ml at the end of 52 weeks which was statistically significant. At 52 weeks 118 (78%) CHB patient became HBV DNA negative. The mean ALT level before treatment were 96.1 ± 70.9 U/L which were 39.7 ± 11.98 U/L at the end of 52 weeks. At 52 weeks of treatment 78 (71.5%) became HBeAg negative. Conclusion: Entecavir significantly suppress HBV DNA level as well as normalization of aminotransfersae level. It has significant influences on HBeAg negativity in HBeAg positive chronic hepatitis B patients.&#x0D; JCMCTA 2019 ; 30 (1) : 12-15

Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses

Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.

Issues Meriting Further Study in Preventing Mother-to-Infant Transmission of Hepatitis B by Antiviral Therapy During Pregnancy

Abstract Mother-to-infant transmission of hepatitis B virus (HBV) is a main cause of chronic HBV infection. Maternal high HBV DNA level or positive hepatitis B e antigen (HBeAg) is the major risk factor for the transmission. With recommended passive and active immunoprophylaxis, the transmission occurs in nearly 0 and 4–12% of infants born to HBV-infected mothers with negative and positive HBeAg, respectively. Therefore, pregnant women with negative HBeAg appear not requiring antiviral therapy to prevent mother-to-infant transmission of HBV. Recent studies demonstrated that oral antivirals (lamivudine, telbivudine, or tenofovir) in pregnant women with high viral load or positive HBeAg, starting from 28–32 weeks of gestation, together with neonatal immunoprophylaxis, can almost completely prevent the transmission, indicating that it does not require antiviral therapy before 28 weeks of gestation. Accumulated evidence showed that the antivirals may be stopped upon delivery, and the infants may receive breast feeding after birth. However, these issues, as well as HBV DNA threshold for antiviral therapy during pregnancy, optimal timing for start and discontinuation of antivirals, and the drug safety of fetuses/infants, require further investigations to optimize the antiviral therapy during pregnancy. The proof of safety of fetal exposure to antivirals needs more evidence, which can be achieved from the real-world data analysis.

Mother-to-child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study.

The objective of this study is to determine whether amniocentesis increases the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) and evaluate risk factors for MTCT. One hundred forty-three hepatitis B surface antigen (HBsAg)-positive women with amniocentesis were enrolled into the amniocentesis group. Six hundred five nonamniocentesis cases were matched with amniocentesis cases based on maternal viral loads, antiviral therapy regimens, and delivery dates. MTCT of HBV was defined as HBsAg and/or DNA positivity in infants from birth to age 7 to 12 months. Mother-to-child transmission rate was significantly higher in HBsAg-positive women with amniocentesis than in those without amniocentesis (2.80% vs 0.50%; relative risk [RR], 5.64; 95% CI, 1.28-24.93). In the amniocentesis group, maternal HBV DNA more than or equal to 7.0 log10 IU/mL and hepatitis B e-antigen (HBeAg) positivity were associated with higher MTCT rates than maternal HBV DNA less than 7.0 log10 IU/mL (10.81% vs 0%, p = .004) and HBeAg negativity (8.16% vs 0%, p = .013), and antiviral therapy reduced MTCT rate from 14.3% to 0% (p = .554) when maternal HBV DNA was more than or equal to 7.0 log10 IU/mL. Amniocentesis increases the risk of MTCT in women with hepatitis B, and maternal HBV DNA more than or equal to 7.0 log10 IU/mL and HBeAg positivity are risk factors for MTCT. Antiviral therapy may be effective to prevent MTCT after amniocentesis in highly viremic mothers.

Comparison of antibody response to hepatitis B vaccination in infants with positive or negative maternal hepatitis B e antigen (HBeAg) in cord blood: implication for the role of HBeAg as an immunotolerogen

ABSTRACT Hepatitis B e antigen (HBeAg) has been considered to cause immunotolerance to hepatitis B virus (HBV) in newborn infants after fetal HBeAg exposure. This study compared anti-HBs responses to hepatitis B vaccination in infants who were born to HBeAg-positive and -negative mothers respectively, to investigate whether fetal HBeAg exposure may induce immunotolerance to HBV. Totally 265 infants who received recommended neonatal immunoprophylaxis against hepatitis B and had no HBV infection were included. Anti-HBs levels were compared between 124 infants with cord blood positive HBeAg and 141 infants with cord blood negative HBeAg at 7–12 months of age. The infants in two groups had similar age at the follow-up (10.0 ± 2.3 vs 10.1 ± 2.3 months, P = 0.590). Overall, 259 (97.7%) of 265 infants achieved anti-HBs levels (mIU/ml) ≥10 and 6 (2.3%) others had anti-HBs <10. Of 124 HBeAg-positive infants at birth, 46.0%, 39.5%, 12.1%, and 2.4% had anti-HBs levels (mIU/ml) ≥1000, 100–999.9, 10–99.9, and <10, respectively. Of 141 HBeAg-negative infants at birth, 35.5%, 48.9%, 13.5%, and 2.1% showed ≥1000, 100–999.9, 10–99.9, and <10, respectively. The proportions of each anti-HBs level between the two groups were comparable (all P > 0.05). Additionally, the distribution of anti-HBs response levels were also comparable in infants with high and low HBeAg levels (P = 0.818). In conclusions, the fetal HBeAg exposure does not inhibit the antibody response to neonatal hepatitis B vaccination. The data suggest that HBeAg appears not inducing immunotolerance to HBV.

HBV and HDV Seroprevalence among Healthy People Admitted for Hepatitis B Vaccination

Background: An estimated 350 million persons worldwide are chronically infected with Hepatitis B virus (HBV). These are at increased risk of developing liver cirrhosis and hepatocellular carcinoma. The aim of the study was to determine the prevalence of Hepatitis B and co- existing Hepatitis D and to investigate the pattern of lab parameters among patients positive for hepatitis B and/or D. Methods: This is an observational cross-sectional prospective study conducted from 2009 to 2014 in Lyari General Hospital Karachi Pakistan. A total of 10270 patients were registered in the liver clinic from June 2009 to December 2014 for hepatitis B vaccination. All patients who had visited the Liver clinic of Lyari General Hospital for hepatitis B vaccination were first screened for hepatitis B, and D viruses by HBsAg, and Anti HDV antibodies and anti HCV by ELISA method. Patients who had HBsAg negative were then vaccinated. If HBsAg was found to be positive the patients have been underwent through further tests for the confirmation of hepatitis B and D (Hepatitis B Virus DNA polymerase chain reaction (PCR), hepatitis B e-antigen (HBeAg), hepatitis Be antibody (HBeAb), and if anti HDV positive then HDV RNA PCR was performed). Patients found to have a positive HBVDNA PCR with positive or negative HBeAg were treated. Patients with positive HBeAb were seroconverted. Patients with a positive anti HDV antibody underwent an HDVRNA PCR and if positive were treated. Statistical analysis was performed using SPSS (IBM SPSS Statistics 24.0). Results: A total of 10270 patients were registered in the liver clinic. Overall 206 (2%) were found to be HBV positive, in which 26.2% had Hepatitis D co-infection. More than half (57.3%) were male and 70.4% were married with the mean age of 33.2 ± 10.9 years. About one-fourth of the total were HbeAg positive (25.2%) and hepatitis D antibody positive (26.2%), while 21% had HDV PCR positive and 6.3% had hepatitis C antibody positive. The mean hemoglobin was 12.2, white cell count 6052.3, viral load of HBV DNA was 44100856.97, SGPT was 63.47, albumin was 4.24 and mean INR was 1.09. Conclusion: Prevalence of Hepatitis B infection was 2% and Hepatitis D infection was present in 26.2% of hepatitis B infected patients. Giriş: Dünya genelinde 350 milyon kişinin Hepatit B virüsü (HBV) ile kronik olarak enfekte olduğu tahmin edilmektedir. Bu kişier karaciğer sirozo ve hepatoselüler karsinom gelişimi riski altındadır. Bu çalışmanın amacı Hepatit B ve ko-enfeksiyon olarak Hepatit D virusunun prevelansını saptamak ve Hepatit B ve/ya Hepatit D pozitif hastalar arasında laboratuvar parametrelerinin örüntülerini inceleyebilmektir. Yöntem: Bu gözlemsel tanımlayıcı-kesitsel prospektif çalışma, 2009-2014 yılları arasında Lyari Genel Hastanesi, Karaçi, Pakistan’da yapıldı. Haziran 2009’dan Aralık 2014’e kadar toplam 10270 hasta karaciğer polikliniği’ne hepatit B aşılaması için kaydolmuştur. Lyari Genel Hastanesi’nde Karaciğer kliniğine hepatit B aşılaması için başvuran hastaların hepsi ilk gelişlerinde ELISA yöntemiyle hepatit B ve D virusleri için HBsAg, Anti HDV antikorları ve anti HCV için tarandılar. HBsAg negatif olan hastalar aşılandı. Eğer HBsAg pozitif bulgulandıysa hastalara hepatit B ve D doğrulaması için ileri testler yapıldı ( Hepatit B virus DNA polimeraz zincir reaksiyonu (PCR), hepatit B e-antijeni (HbeAb) ve eğer anti HDV pozitif ise HDV RNA PCR uygulandı). Pozitif HBVDNA PCR sonucu ile pozitif ya da negatif HbeAg sonucu olan hastalar tedavi edildi. İstatiksel yöntem olarak SPSS kullanıldı (IBM SPSS Statistics 24.0). Bulgular: Karaciğr kliniğine toplamda 10270 hasta kaydoldu. Bunlardan 206’sı (%2) HBV pozitif olarak bulgulandı ki %26.2’de Hepatit D ko-enfeksiyonu vardı. Yarısından fazlası (%57.3) erkekti ve %70.4’ü evliydi, yaş ortlaması ise 33.2 ± 10.9 yıldı. Bütünün dörte birinde HBsAg pozitif (%25.2) ve hepatit D antikoru pozitif (%26.2) iken %21 HDV pozitif ve %6.3 hepatit C antikoru pozitifti. Ortalama hemoglobin değeri 12.2, beyaz küre sayısı 6052.3, HBV DNA’nın viral yükü 44100856.97, SGPT 63.47, albumin 4.24 ve ortalama INR 1.09 idi. Sonuç: Hepatit B enfeksiyonu prevelansı %2’dir ve Hepatit D ise hepatit B ile enfekte hastaların %26.2’sinde bulunmaktadır.

Real-world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load.

Data on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real-world setting are limited. To investigate TDF for preventing vertical transmission of HBV in real-world practice. Hepatitis B e-antigen (HBeAg)-positive mothers with HBV-DNA >6log10 IU/mL to receive TDF between gestational weeks 24-33 and delivery were prospectively enrolled and followed until post-partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV-DNA level suppression (<200000IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study. Among 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV-DNA<200000IU/L. On-treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post-partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention-to-treat) and 0% (per-protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation. TDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real-world setting. There were no safety concerns during the postpartum 28-week follow-up. Registry number: Chinese Clinical Trial Registration No. ChiCTR-OIC-17010869.