Chronic hepatitis B (CHB) and hepatitis D (CHD) remain global health challenges, where sustained care engagement, treatment adherence and regular monitoring are essential but often limited by stigma and healthcare access. Digital health tools offer new opportunities to bridge these gaps. This study aimed to adapt the NORA mobile health app for CHB and CHD patients and evaluate its real-world utility in improving knowledge, adherence, communication and quality of life. We conducted a prospective, comparative study (February 2022-April 2024) including adult CHB (HBsAg-positive, HBeAg-negative) or CHD (anti-HDV or HDV-RNA-positive) patients with mobile access and Spanish proficiency. The app offered educational content, medication reminders, quality-of-life questionnaires (CLDQ, FACIT-F, EQ-5D-5L), a chat function and a knowledge test. Sociodemographic, clinical and usage data were analysed. Of 406 patients evaluated (356 CHB, 50 CHD), 277 CHB and 41 CHD patients were eligible. Participation was high (CHB: 88.4%; CHD: 90.2%), with active use in 48.1% and 70.3%, respectively. App users were more often male and Caucasian, and CHD users more frequently had detectable HDV-RNA. Patients with inactive HBV infection were less likely to use the app over the medium term (OR = 0.462, p = 0.003), and those who did use the app missed fewer clinic visits than nonusers (8.4% vs. 18.1%; OR = 0.41, p = 0.016). Among users, 85 were on antiviral therapy, 67% used the medication reminder, and chat use was higher in CHD and in treated patients (p = 0.004). High adherence (68% CHB, 84% CHD) and knowledge gains were observed, particularly in CHB with higher education. CHD patients showed worse baseline quality of life and greater declines over time. This first real-world study of a tailored mobile health (mHealth) app for CHB and CHD showed improved patient knowledge, adherence, communication and quality-of-life monitoring, with greater engagement in patients with advanced disease.

Although current guidelines classify the natural history of chronic hepatitis B (CHB) into several immune phases, a substantial proportion of patients with CHB do not meet criteria for any of the defined immune phases and are considered to be in an indeterminate phase. We aim to perform a meta-analysis to systematically evaluate the prevalence, clinical presentation and outcome of indeterminate CHB patients classified according to American Association for the Study of Liver Diseases (AASLD) 2018 guidelines or European Association for the Study of the Liver (EASL) 2017 guidelines. We searched four databases from inception to Aug 21, 2024, for studies reporting the prevalence, characteristics and/or clinical outcomes of patients with indeterminate CHB classified according to AASLD 2018 guidelines or EASL 2017 guidelines. Of the 4553 studies initially identified, 50 studies met study inclusion criteria and were analysed. The prevalence of indeterminate patients was 38.90% (95% CI: 33.51-44.57) and 38.81% (95% CI: 31.22-46.99) by AASLD 2018 and EASL 2017 guidelines, respectively. Among indeterminate CHB patients, the pooled incidence rate per 1000 person-years for hepatocellular carcinoma and liver-related events was 5.36 (95% CI: 1.38-9.35) and 7.27 (95% CI: 0.00-22.21) per AASLD 2018 guidelines and 5.20 (95% CI: 1.41-8.99) and 9.79 (95% CI: 0.00-25.35) per EASL 2017 guidelines, respectively. Indeterminate phase affects nearly 40% of CHB patients who are at risk for hepatocellular carcinoma and liver-related adverse outcomes. Further research is needed to inform treatment strategies specifically tailored for the indeterminate CHB patients.

E-cigarette switching, smoking cessation, and the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nationwide cohort study in South Korea.

Since there are currently few antiviral drugs that can effectively reduce hepatitis B surface antigen levels, the recurrence rate remains high in patients with chronic hepatitis B (CHB) after discontinuing nucleoside analogues (NAs) treatment. This study aims to provide recommendations for monitoring relapse after treatment cessation, while also elucidating the significance of HBV RNA in predicting relapse in CHB patients. Studies published between 2019 and 2025 were searched using PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and Cqvip. There are 21 cohort studies included and 2043 individuals involved. In our study, HBV RNA-positive individuals had a 1.9-fold higher viral relapse (VR) rate and a 2.26-fold higher clinical relapse (CR) rate compared to negative patients (all p < 0.0001). Subgroup analyses indicated that HBeAg positive at baseline was associated with higher rates of CR (p = 0.006) and no significant correlation between longer follow-up period following the cessation of NAs therapy (≥ 2 years) and higher VR or CR. For each log10 copies/ml increase in HBV RNA levels at discontinuation, there was a 1.32-fold increase in VR and a 1.37-fold increase in CR (all p < 0.0001). Our findings evaluated the relationship between HBV RNA status and levels at the time of NAs discontinuation and post-discontinuation relapse, highlighting HBV RNA as a helpful post-treatment biomarker for predicting relapse. HBV RNA surveillance is essential for patients discontinuing therapy following NAs, particularly for those who are HBeAg-positive at baseline.

Renal safety is an important consideration for treatment selection in chronic hepatitis B (CHB) because of the ageing population and increasing prevalence of medical comorbidities. However, the renal safety profiles of first-line nucleos(t)ide analogues (NUCs) for CHB-tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) have not been comprehensively reviewed. To evaluate the renal safety of ETV, TDF, and TAF in general and special populations with CHB. In this narrative review, relevant studies in PubMed were identified using a range of keywords, followed by manual screening of reference lists to capture additional sources. Based on current randomised and real-world evidence, TDF may cause more nephrotoxic effects than ETV in patients with pre-existing moderate-to-severe chronic kidney disease (CKD), but the two agents may have similar renal safety profiles among patients with no or mild baseline renal impairment. Randomised data showed that TAF is significantly less nephrotoxic than TDF in different clinical settings. Retrospective data from both treatment-naïve and -experienced patients, as well as special populations, including patients with renal impairment, kidney transplant, advanced age, and acute-on-chronic liver failure, indicated that TAF may be more likely to improve renal function compared to ETV. Current first-line NUCs show comparable renal safety profiles in CHB patients with no or mild kidney dysfunction, with growing evidence that favours TAF. Future prospective studies are needed to validate these findings, and more research should focus on CHB patients with diabetes mellitus who are at risk of CKD.

A machine learning model for predicting complete virological response in chronic hepatitis B patients receiving first-line nucleos(t)ide analogues therapy.

The development of novel agents with curative intent for chronic hepatitis B (CHB) has accelerated, but few candidates transition to phase III trials. We evaluated trial design features associated with registry-defined trial completion and phase transition, and synthesized end-of-treatment hepatitis B surface antigen (HBsAg) decline as an on-treatment antiviral signal. We systematically reviewed clinical trial registries and bibliographic databases for CHB cure trials. Associations between trial design characteristics and trial performance were analyzed using Cox regression (time to registry-defined completion), logistic regression (phase I to phase II transition), and random-effects meta-analysis of end-of-treatment HBsAg decline. Larger sample size (HR = 0.819, 95% CI = 0.710-0.945) and longer treatment duration (HR = 0.897, 95% CI = 0.816-0.987) were associated with a lower likelihood of registry-defined completion in phase I trials. In phase II trials, larger sample size was associated with a lower likelihood of registry-defined completion (HR = 0.936, 95% CI = 0.879-0.997). Novel trial designs were not associated with faster completion. Among phase I trials with a definitive status, trials enrolling healthy volunteers were more often followed by phase II registration (adjusted OR = 2.82, 95% CI = 1.16-7.08). Meta-analysis showed that direct-acting antivirals were associated with marked end-of-treatment HBsAg decline (SMD = 1.28, 95% CI = 0.47-2.08). Smaller and shorter early-phase trials were more likely to complete, whereas novel trial designs were not associated with faster completion. Direct-acting antivirals showed marked end-of-treatment HBsAg decline, an on-treatment signal rather than durable functional cure.

The prerequisite for achieving the goal of the World Health Organization to completely eliminate viral hepatitis by 2030 is China's accurate understanding of the current disease burden, thereby providing a basis for formulating and optimizing intervention measures. Based on the Global Burden of Disease (GBD) 2023 dataset, we extracted data on acute hepatitis A, B, C, and E in China, including incidence, mortality, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs). To account for differences in age and sex distributions, we calculated ASRs based on the age-specific data extracted from the GBD 2023 dataset. To further assess temporal patterns across different age groups, we estimated the average annual percent change (AAPC). We applied the autoregressive integrated moving average model to project acute viral hepatitis (AVH) disease burden for 2024-2030. In 2023, there were an estimated 48.7 million incidence cases of AVH in China, including approximately 19.0 million cases of acute hepatitis A (AHA), 19.2 million cases of acute hepatitis B (AHB), 1.35 million cases of acute hepatitis C (AHC), and 9.2 million cases of acute hepatitis E (AHE). From 1990 to 2023, the overall age-standardized incidence rates (ASIR) of the four major AVH types in China declined (AAPC = -0.90%, 95% confidence interval [CI]: -0.93 to -0.87%). In the previous decade, divergent trends were observed. The ASIR of AHC increased (AAPC = 1.42%, 95% CI: 1.39-1.46%), AHE remained stable (AAPC = -0.04%, 95% CI: -0.39-0.32%), whereas AHA and AHB decreased. Moreover, the age-standardized mortality and DALYs rates for AVH significantly decreased. Age-specific analysis further revealed an upward trend in standardized incidence among individuals aged 25-29 years (AAPC = 0.14%, 95% CI: 0.10-0.19%). A continued decline in the ASIR of AVH is projected for 2024-2030. In China, the overall burden of AVH has decreased between 1990 and 2023. AHB vaccination among younger populations should be strengthened, and targeted prevention and control strategies should be implemented for those at high risk of AHC, to curb the spread of the disease and reduce the overall burden.

Concomitant metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in patients with chronic hepatitis B (CHB), yet its impact on liver-related outcomes remains controversial. Although the stimulator of interferon genes (STING) pathway is pivotal in innate immunity, its involvement in CHB-MASLD comorbidity is undefined. We aimed to elucidate the role and mechanism of macrophage STING in CHB-MASLD comorbidity. Human and mouse liver tissues were used to assess STING expression levels. Myeloid-specific STING knockout and hepatocyte-specific STING knock-in mice were used to explore the effects of STING in comorbidity. Tohoku Hospital Pediatrics (THP)-1 and HepG2.2.15/HepG2-NTCP co-cultured cells were stimulated with palmitic acid (PA) for 12 hours in vitro for mechanism research. Markers for STING, autophagy and endoplasmic reticulum stress (ERS) were assessed using western blot analysis, immunohistochemistry and immunofluorescence assays. The liver organoids were used for validation. CHB-MASLD comorbidity in mice decreased HBV replication but accelerated liver inflammation and fibrosis, linked to aberrant STING upregulation in macrophages. HBV synergised with lipotoxicity to disrupt Rab7 expression and function in macrophages, impairing STING degradation via autophagic-lysosomal and endosomal-lysosomal pathways. Pathological STING accumulation had dual effects: cytosolic STING enhanced antiviral activity (TANK-binding kinase 1-interferon regulatory factor 3-interferon beta) and promoted inflammation (nuclear factor kappa-B/NOD-like receptor family pyrin domain-containing 3 (NLRP3)). Extracellular vesicles transported STING to hepatocytes, triggering ERS (PKR-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP)), further activating NLRP3 and exacerbating injury. Therapeutically, restoring Rab7 facilitated STING degradation, attenuating pathology. In CHB-MASLD comorbidity, impaired Rab7 function leads to aberrant STING accumulation in macrophages, suppressing HBV replication but paradoxically accelerating liver disease progression. Targeting Rab7 to degrade excessive STING represents a novel therapeutic strategy.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with chronic hepatitis B (CHB) accounting for more than half of the cases. Regular surveillance, including abdominal ultrasonography with alpha-fetoprotein testing every 6 months, enables early tumor detection and curative treatment; however, current guideline recommendations based mainly on age, sex, and race/ethnicity insufficiently capture individual risk variation, particularly among patients with CHB who do not have cirrhosis. In addition, real-world adherence to HCC surveillance is suboptimal-fewer than 40% of eligible patients receive surveillance at the recommended 6-month intervals. To improve both efficiency and impact, surveillance resources should be reallocated to patients whose estimated risk exceeds the cost-effective surveillance threshold. Recent studies support biomarker-based risk stratification as a more precise approach. For example, in untreated CHB, HBeAg-negative patients meeting inactive disease criteria with HBsAg <100IU/mL have an annual HCC incidence below the 0.2% cost-effectiveness threshold, suggesting that routine surveillance may be unnecessary. In antiviral-treated CHB, models such as PAGE-B and its derivatives can accurately identify low-risk patients who may safely forgo HCC surveillance. Conversely, for patients at extremely high risk, including those with cirrhosis, intensified strategies-such as abbreviated MRI or combined biomarker algorithms-may enhance early detection. Collectively, these findings support a transition from a categorical, one-size-fits-all approach toward a precision surveillance paradigm that tailors the need for and intensity of HCC surveillance to biomarker-defined risk, thereby optimizing resource use, improving adherence, and maximizing clinical benefit. Nevertheless, further large-scale, prospective studies across diverse populations are needed to validate biomarker thresholds and confirm the long-term safety of exempting very-low-risk patients with CHB from HCC surveillance.

The global prevalence of chronic hepatitis D virus (HDV) is estimated to be 4%-5%. Our aim was to determine the prevalence of HDV exposure in patients with chronic hepatitis B (CHB) in three different healthcare systems based in San Diego (SD) County and Los Angeles (LA) County of California. We retrospectively reviewed all adult CHB patients screened for anti-HDV IgG antibody (HDV Ab) who were seen from 2010 to 2024 in the hepatology clinics at Scripps Clinic (SC) in La Jolla, California, and La Maestra Clinic (LM) in SD, and from 2019 to 2023 at UCLA. We determined the median household income by ZIP Code to stratify all patients by socioeconomic status (SES). At SC, 593 of 2441 patients with CHB were screened for HDV. A total of 14 patients tested positive for HDV Ab (2.4%). Two of the 14 patients had detectable HDV RNA. At LM, 118 of 312 patients with CHB were screened for HDV and three patients had a positive HDV Ab (2.5%). None had detectable HDV RNA. At UCLA, 234 of 267 patients with CHB were screened for HDV, and 10 patients had a positive HDV Ab (4.3%). One patient had detectable HDV RNA. Most patients screened at LM, SC, and UCLA belonged to the lowest median yearly income ($75,281), middle ($101,105), and high ($123,271) categories, respectively. There was no statistically significant difference in the prevalence of HDV Ab among each cohort. Of almost a thousand CHB patients who were screened for HDV exposure across three healthcare systems, the prevalence of HDV Ab-positive patients was 2.4%-4.3% without statistically significant differences. Patients from LM, SC, and UCLA were representative of low, middle, and high socioeconomic groups, respectively. This suggests that SES may be less of a risk factor for HDV infection. The HDV PCR-positive (chronic infection) rates were low, ranging from 0% to 0.4%.

SOX6 is a novel host factor that promotes hepatitis B virus replication by enhancing the transcriptional activity of enhancer I.

Hepatitis B virus induces T cell exhaustion by increasing mitochondrial ROS accumulation.

In China, a significant number of individuals with chronic hepatitis B (CHB) are at risk of developing hepatocellular carcinoma (HCC). Due to low surveillance rates and guidelines that inadequately address resource constraints, this study evaluates the cost-effectiveness of risk-based HCC surveillance strategies in CHB patients in China. We developed a state-transition model to simulate disease progression in hypothetical CHB cohorts over their lifetimes, considering various HCC risk scores to classify patients into low, intermediate, and high-risk categories. The model assessed the cost-effectiveness of five active surveillance strategies, including biannual monitoring, compared to no surveillance. Key outcomes included life expectancy, quality-adjusted life years (QALYs), total costs, and the incremental cost-effectiveness ratio (ICER), with comparisons to China's willingness-to-pay (WTP) threshold of $37,674 per QALY. For overall and intermediate-risk cohorts, biannual and annual surveillance were cost-effective (ICER < $37,674/QALY). In high-risk groups, all surveillance strategies, except quinquennial, were cost-effective, with ICERs ranging from $28,448 to $36,073 per QALY. No surveillance strategy was cost-effective for the low-risk group. Sensitivity analyses confirmed biannual surveillance had the highest probability of being cost-effective across all risk groups and was most sensitive to changes in mortality rates associated with intermediate to advanced HCC stages. The cost-effectiveness of HCC surveillance in CHB patients varies based on HCC risk. A risk-stratified approach, with biannual surveillance prioritized for high-risk patients and potentially omitted for low-risk patients, could optimize resource allocation.

Higher incidence of HBeAg seroclearance with tenofovir alafenamide fumarate than entecavir in HBeAg-positive patients with chronic hepatitis B.

Anti-interferon-α antibodies and HBsAg seroclearance during peginterferon-α therapy in chronic hepatitis B.

Background/Objectives: Chronic hepatitis B (CHB) and type 2 diabetes mellitus (T2DM) frequently coexist. This study aimed to investigate the impact of T2DM and glycemic control on antiviral efficacy in CHB patients. Methods: This single-center, retrospective cohort study included treatment-naïve CHB patients who initiated nucleos(t)ide analogue (NA) therapy between January 2019 and January 2024. The primary endpoint was a complete virological response (CVR), defined as achieving HBV DNA levels below 20 IU/mL after 48 weeks of treatment. Results: The CHB + T2DM group (n = 81) demonstrated a significantly lower CVR rate than the CHB group (n = 106) (26.0% vs. 41.2%, p = 0.038). Multivariate analysis identified T2DM as an independent negative predictor of a CVR (OR = 0.400, 95% CI: 0.196-0.815, p = 0.012). Within the CHB + T2DM subgroup, adequate glycemic control (HbA1c < 7%) was associated with a higher CVR (38.7% vs. 16.7%, p = 0.034). Patients newly diagnosed with diabetes at enrollment showed a higher rate of HBeAg loss than those with pre-existing diabetes (57.1% vs. 10.0%, p = 0.036). Regarding antiviral regimens, entecavir-treated CHB + T2DM patients had a lower CVR than CHB controls (18.8% vs. 46.2%, p = 0.015). Furthermore, tenofovir-based regimens showed a more favorable antiviral trend than entecavir in CHB patients with T2DM. Conclusions: Comorbid T2DM was an independent risk factor for impaired antiviral efficacy in CHB patients. Optimal glycemic control may improve virological outcomes. These findings suggest that the early diagnosis and management of T2DM could enhance antiviral treatment efficacy in CHB patients.

BACKGROUNDAs a novel antiviral agent, the comparative renal safety of tenofovir amibufenamide (TMF) vs entecavir (ETV) in chronic hepatitis B (CHB) remains unclear.AIMTo compare changes in the estimated glomerular filtration rate (eGFR) between TMF and ETV in previously untreated patients with CHB over 48 weeks.METHODSWe retrospectively analyzed clinical records of 187 treatment-naive patients with CHB receiving TMF or ETV for ≥ 48 weeks from June 2021 to January 2025. Patients were allocated to the TMF (n = 48) or ETV (n = 139) group based on their antiviral drug therapy. Propensity score matching (2:1) was used to balance baseline clinical characteristics. eGFR changes at 48 weeks were compared. Patients were then stratified into normal and abnormal eGFR groups, and factors associated with abnormal eGFR were analyzed.RESULTSAfter propensity score matching, 48 patients and 96 patients were stratified into the TMF and ETV group, respectively. At baseline, the two groups had comparable clinical characteristics, with no significant differences (P > 0.05). Baseline eGFR values were 111.83 mL/minute/1.73 m2 for the TMF group and 112.50 mL/minute/1.73 m2 for the ETV group (P = 0.712). At week 48, eGFR declined in both groups, but the ETV group experienced a significantly greater reduction relative to the TMF group (106.10 mL/minute/1.73 m2vs 111.01 mL/minute/1.73 m2; P = 0.019). In univariate analysis, the groups differed significantly in terms of age, serum albumin, triglyceride, and baseline eGFR (all P < 0.05). Multivariate analysis identified baseline eGFR and triglyceride as independent predictors of abnormal eGFR by 48 weeks (P < 0.05).CONCLUSIONIn treatment-naïve patients with CHB, ETV treatment exhibited a strong association with an increased risk of decreased eGFR levels at 48 weeks in comparison with TMF.

This study investigated the effectiveness of a protocol-based pharmacotherapy management (PBPM) system in preventing hepatitis B virus (HBV) reactivation induced by chemotherapy. This protocol requires pharmacists to verify orders for hepatitis B (HB) surface antigen (HBsAg), anti-HB core antibody (HBcAb), anti-HBs antibody (HBsAb), and HBV-deoxyribonucleic acid (DNA) tests before the start of chemotherapy. Pharmacists are also required to enter any missing test orders after confirming them with physicians. We retrospectively compared the implementation rates of HBsAg, HBcAb, HBsAb, and HBV-DNA tests using the chi-squared test across the following three periods: the pre-PBPM system implementation (pre-PBPM) period (July to September 2021; n=203), the ≤6 month post-PBPM system implementation (≤6M post-PBPM) period (November 2021 to April 2022; n=453), and the >6 month post-implementation (>6M post-PBPM) period (May to July 2022; n=245). The implementation rate of HBsAg tests remained at 100% throughout the entire study period. The overall HBsAg positivity rate was 2.0% (18/901). The implementation rates of HBcAb/HBsAb tests increased significantly, from 59.6% (121/203; pre-PBPM period) to 91.2% (413/453; ≤6M post-PBPM period, p<0.001) and to 98.0% (240/245; >6M post-PBPM period, p<0.001). The HBcAb/HBsAb positivity rates and HBV-DNA implementation rates in the respective periods were 33.1% (40/121), 26.9% (111/413), and 23.8% (57/240), and 90.0% (36/40), 89.2% (99/111), and 91.2% (52/57), with no statistically significant differences observed. No cases of HBV reactivation were observed during the study period. Introduction of the PBPM system significantly contributed to the improvement in the implementation rates of HBsAb/HBcAb testing.

Hepatitis B virus (HBV) replication generates a double-stranded linear DNA (dslDNA) byproduct. This dslDNA can undergo intermolecular and intramolecular nonhomologous end-joining (NHEJ) recombination, resulting in viral integration and dslDNA-derived covalently closed circular DNAs (dsl-cccDNAs), respectively. The insertions and deletions (INDELs) at the end-joining site have been used to differentiate dsl-cccDNA from the authentic cccDNA. The prevalence and characteristics of dsl-cccDNA in chronic hepatitis B (CHB) patients remain unclear. HBV-targeted next-generation sequencing (NGS) was used to identify 32 dsl-cccDNA-positive candidates, 22 HBeAg(+) and 10 HBeAg(-), from 56 liver biopsies of antiviral treatment-naïve CHB patients for dsl-cccDNA confirmation and characterization by PSAD-cccDNA PCR NGS. INDELs within the DR2-1 region (nt 1600-1840) of the cccDNA were analyzed. Various clonally expanded, heterogenous ~22-nt deletions in the X gene region around nt 1760 were discovered in all 32 samples. The dsl-cccDNA species were then defined and characterized by the INDELs clustered at the DR1 surrounding region (nt 1800-1840). The proportion of dsl-cccDNA in total cccDNA was higher among HBeAg(+) compared to HBeAg(-) samples. The diversity of dsl-cccDNA species positively correlated with cccDNA levels and serum viral load, and was higher in HBeAg(+) CHB. dsl-cccDNA is more abundant and diverse among the HBeAg(+) CHB subjects. The existence of replication-defective dsl-cccDNA may facilitate immune evasion and HBV integration, and complicate HBV pathogenesis.