Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

UNASSIGNED: The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.
UNASSIGNED: We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.
UNASSIGNED: The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity (I 2 = 54%, p <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity (I 2 = 0.00%, p = 1.00).
UNASSIGNED: Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.
UNASSIGNED: Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.

UNASSIGNED: HBV exhibits wide genetic diversity with at least 9 genotypes (GTs), which differ in terms of prevalence, geographic distribution, natural history, disease progression, and treatment outcome. However, differences in HBV replicative capacity, gene expression, and infective capability across different GTs remain incompletely understood. Herein, we aimed to study these crucial aspects using newly constructed infectious clones covering the major HBV GTs.
UNASSIGNED: The replicative capacity of infectious clones covering HBV GTs A-E was analyzed in cell lines, primary hepatocytes and humanized mice. Host responses and histopathology induced by the different HBV GTs were characterized in hydrodynamically injected mice. Differences in treatment responses to entecavir and various HBV capsid inhibitors were also quantified across the different genetically defined GTs.
UNASSIGNED: Patient-derived HBV infectious clones replicated robustly both in vitro and in vivo. GTs A and D induce more pronounced intrahepatic and proinflammatory cytokine responses which correlated with faster viral clearance. Notably, all 5 HBV clones robustly produced viral particles following transfection into HepG2 cells, and these particles were infectious in HepG2-NTCP cells, primary human hepatocytes and human chimeric mice. Notably, GT D virus exhibited higher infectivity than GTs A, B, C and E in vitro, although it was comparable to GT A and B in the human liver chimeric mice in vivo. HBV capsid inhibitors were more readily capable of suppressing HBV GTs A, B, D and E than C.
UNASSIGNED: The infectious clones described here have broad utility as genetic tools that can mechanistically dissect intergenotypic differences in antiviral immunity and pathogenesis and aid in HBV drug development and screening.
UNASSIGNED: The hepatitis B virus (HBV) is a major contributor to human morbidity and mortality. HBV can be categorized into a number of genotypes, based on their specific genetic make-up, of which 9 are well known. We isolated and cloned the genomes of 5 of these genotypes and used them to create valuable tools for future research on this clinically important virus.

Hepatitis B e antigen (HBeAg) seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B patients. This study aimed to explore whether hepatitis B virus (HBV) RNA serum levels can predict HBeAg seroconversion treated with entecavir.
Serum samples from HBeAg-positive children previously treated with entecavir were retrospectively analyzed. HBV RNA levels were measured at baseline, weeks 12, 24, 48, 72 of therapy. Ability of individual biomarkers to predict HBeAg seroconversion was evaluated using receiver operating characteristics (ROC) analyzes.
Serum HBV RNA was detectable in 51 children with a median of 6.05 (4.04-8.29) log10 IU/mL at baseline. Patients with subsequent HBeAg seroconversion showed a significantly larger decline in median HBV RNA levels during treatment from baseline to week 12 of 1.96 (0.30-3.38) and to week 24 of 2.27 (1.20-3.38) log10 IU/mL, respectively, in comparison to HBeAg-positive patients without HBeAg seroconversion (P < 0.001). Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (area under ROC scores > 0.85, P < 0.001).
On-treatment HBV RNA dynamic predicts entecavir-induced HBeAg seroconversion in children with chronic hepatitis B living in China.

UNASSIGNED: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC.
UNASSIGNED: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively.
UNASSIGNED: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78-0.82). NPVs were always >99% (99.3-100%), whereas PPV ranged between 13% and 24%.
UNASSIGNED: In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease.
UNASSIGNED: Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.

UNASSIGNED: Chronic Hepatitis B (CHB) is a global health problem affecting around 400 million of people worldwide. Two available first-line antiviral drugs are tenofovir disoproxil fumarate (TDF) and Entecavir (ETV). Till date,there are few published reports from India comparing efficacy of TDF and ETV in CHB cases. Therefore, this present study was carried out with an aim to compare the efficacy of ETV and TDF in patients with nucleos(t)ide naïve CHB.
UNASSIGNED: This retrospective cohort study was carried out in 192 treatment naïve CHB cases, who completed 24 months of treatment with either TDF or ETV between March 2015 and August 2017. The primary end point of the study was undetectable hepatitis B virus DNA after 24 months of therapy.
UNASSIGNED: Of total 192 patients with CHB, 38 hepatitis B e-antigen (HBeAg)-positive and 53 HBeAg-negative patients were treated with tenofovir, whereas 40 HBeAg-positive and 61 HBeAg-negative patients were treated with ETV. Pretreatment characteristics at baseline were not statistically different between the TDF and ETV groups. Patients treated with TDF achieved significantly higher complete viral suppression as compared with ETV-treated patients (Log rank: 7.04, P = 0.008) in HBeAg-positive CHB during the 24 months follow-up time; whereas no significant difference in viral suppression rate could be noticed in HBeAg-negative patients (Log rank: 0.98, P = 0.38). Both univariate and multivariate analysis by cox proportional hazard model confirmed that tenofovir had significant rate of complete viral suppression in comparison with ETV in HBeAg-positive patients (P < 0.05); whereas complete viral suppression rates were similar in HBeAg-negative patients.
UNASSIGNED: In our study, tenofovir had more effective antiviral suppressive effect compared with ETV in HBeAg-positive, nucleos(t)ide-naïve CHB cases.

UNASSIGNED: Hepatitis B virus reactivation (HBVR) is common in patients withcancer. The aim of the present study was to find out clinical profile of patients with cancer receiving chemotherapy with HBVR and to study the efficacy of entecavir (ETV) and tenofovir in the treatment of HBVR.
UNASSIGNED: This is a prospective study in which all consecutive patients with cancer with evidence of HBVR were included. HBVR was defined as: New onset transaminitis with alanine aminotransferase (ALT) >3 times upper limit of normal and >10 fold increase in HBV DNA levels from baseline levels or detection of HBV DNA ≥100,000 IU/ml in patients with no baseline HBV DNA. Patients with HBVR were put on ETV or tenofovir and were closely monitored for efficacy and safety for minimum of 1 year.
UNASSIGNED: Of 204 Hepatitis B surface antigen (HBsAg)-positive patients with different cancers, 92 met the inclusion criteria. Of 92, 46 received ETV 0.5 mg/day and 46 received tenofovir disoproxil fumarate (TDF) 300 mg/day. At 6 months, there was 4.7 log reduction in HBV DNA level in the ETV group and 5.2 log reduction in the TDF group (P = 0.029). Proportion of patients with undetectable HBV DNA (75.7% vs 87.5%), ALT normalization (89.2% Vs 87.5%), HBsAg negativity (25% vs 28.1%), and seroconversion (2.8% vs 3.1%) at 1 year were almost similar in both groups with P value > 0.05 for all efficacy end points. There was no HBVR-related mortality in any group.
UNASSIGNED: Both ETV and tenofovir are very effective in the treatment of HBVR and reduce the liver-related mortality and morbidity in such patients.

UNASSIGNED: Nucleos(t)ide analogues (NUCs) effectively suppress serum HBV DNA. Previously, we have identified 21 patients with undetectable covalently closed circular DNA (cccDNA) upon long-term NUC therapy. This study investigated the effect of NUC withdrawal in patients with undetectable cccDNA.
UNASSIGNED: Nineteen patients on long term NUCs (median 13.4 years) were recruited: 13 were randomized to discontinue NUCs; 6 to continue taking NUCs. All had undetectable cccDNA at the time of last liver biopsy (median time 2.9 years prior to randomization). Serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), liver biochemistry, and serum HBV RNA were monitored.
UNASSIGNED: At the time of randomization, all patients had undetectable serum HBV DNA and HBV RNA. Twelve of the 13 patients had HBV DNA rebound to 100 IU/ml within 20 weeks of NUC discontinuation. The thirteenth patient had HBV DNA rebound at week 70. Three patients experienced biochemical flares after re-treatment which subsequently resolved. There was no significant association between the time of HBV DNA rebound and baseline HBsAg, HBcrAg and alanine aminotransferase, duration of treatment, and age at which treatment was stopped (all p >0.05). At the time of HBV DNA rebound, HBV DNA levels correlated with HBcrAg levels (p = 0.003), but not with HBsAg levels (p = 0.262).
UNASSIGNED: In patients with undetectable intrahepatic cccDNA, virologic rebound still occurred after NUC cessation. At the rebound of HBV DNA, the kinetics of HBsAg production were independent of those of viral DNA replication. Additional studies are required to determine the factors that may predict virologic rebound and when NUCs can be discontinued in HBsAg-positive patients with chronic hepatitis B.
UNASSIGNED: It has been shown that following long-term nucleos(t)ide analogue treatment for chronic hepatitis B, some patients have undetectable levels of viral DNA in their livers. We tested the results of withdrawing nucleos(t)ide analogue treatment in these patients and found that viral relapse could occur in patients with undetectable viral DNA. Further research is required to determine whether nucleos(t)ide analogue treatment can be discontinued in specific patients with chronic hepatitis B.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

UNASSIGNED: In Pakistan, approximately 4.5 million people are afflicted with chronic hepatitis B (CHB). The compliance with hepatitis B virus (HBV) management guidelines is still unknown. This was the first study from Pakistan in which the knowledge and practices of treating physicians were compared with three standardized guidelines (Asia Pacific Association for the Study of the Liver (APASL) 2012/European Association for the Study of the Liver (EASL) 2012/American Association for the Study of Liver Diseases (AASLD) 2009).
UNASSIGNED: A cross-sectional study was conducted during 2014-2015 at four tertiary care teaching hospitals of Karachi, Pakistan. The study participants were internists, gastroenterologist, senior residents who were involved in the management of CHB patients. All participants were offered to fill the study questionnaire.
UNASSIGNED: A total of 179 physicians (103 residents, 76 consultants) participated. Mean age of participant was 35 ± 9.3 years. Approximately one-third of them followed AASLD (27.3%) and EASL (24.0%) guidelines. Entecavir, tenofovir or Peg IFN ∞ 2a were considered as first line therapy by 43%, 38.5% and 30.2% respectively. However, 17.9% preferred entecavir with tenofovir for rescue therapy, 25.7% and 23.5% preferred tenofovir or entecavir as both first line and rescue therapy respectively. Serum HBV DNA, alanine transaminase levels were used to monitor during oral antivirals therapy by 45.3%. hepatocellular carcinoma screening was considered for all HBV cases by 51.4% using ultrasound (55.3%) and alfa fetoprotein (52.5%) every 6 months.Overall 40.2% participants had poor knowledge about indication of liver biopsy, treatment initiation and antiviral prophylaxis. Significant association was found between grades of knowledge and gender, age group, designation and specialty (P < 0.05). Younger physicians, consultants (age 25-40 years) and those who were practicing gastroenterology/hepatology were more likely to have higher knowledge scores in compliance with the guidelines as compared to others.
UNASSIGNED: Our study highlighted the gaps in knowledge and practices in managing CHB patients according to guidelines. Efforts to improve knowledge, refresher courses and appropriate coordination between gastroenterologists and internal medicine physicians could enable management and follow-up of patients with CHB effectively.