Search

Background: While previous reports have shown that hepatitis B virus (HBV) infection affects lipid metabolism and vice versa, the impact of dyslipidemia on the functional cure of HBV infection following peginterferon alfa (PegIFNα) therapy remains unknown. Hence, this study aimed to investigate the effect of dyslipidemia on hepatitis B surface antigen (HBsAg) clearance and develop a nomogram model for predicting patients for whom PegIFNα therapy is indicated. Methods: A total of 160 nucleos(t)ide analogues (NAs)- experienced chronic hepatitis B (CHB) patients treated with PegIFNα (180 µg/week) were enrolled in this study. The relationship between serum lipid and HBsAg clearance was analysed. Univariate and multivariate COX analyses were used to construct and plot the nomogram model. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. Results: After 48 weeks of PegIFNα therapy, a total of 33 patients in the cohort achieved HBsAg clearance. Univariate and multivariate COX analyses indicated that dyslipidemia was significantly associated with HBsAg clearance and was an independent predictor of HBsAg clearance (HR = 0.243, P = 0.001). Kaplan-Meier survival analyses show that cumulative HBsAg clearance was significantly higher in the normolipidemic group than in the dyslipidemia group (log-rank test, P = 0.007). During the treatment, triglyceride showed an increasing trend, while the levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1 and apolipoprotein B decreased. Dyslipidemia and other indicators independently associated with HBsAg clearance were used to construct the nomogram model. The AUC of the model at 36-week and 48-week were 0.879 and 0.856, and the model demonstrated good discrimination and calibration. Conclusion: Dyslipidemia can affect the antiviral efficacy of PegIFNα in NAs-experienced CHB patients. Our findings suggest that the nomogram model constructed using serum lipid has good predictive power and may help physicians to identify the superior patients for PegIFNα therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions 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. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aims to assess the efficacy and safety of adding pegylated interferon (Peg-IFN) to long-term nucleos(t)ide analogs (NAs) treatment for achieving functional cure in patients with chronic hepatitis B (CHB). Methods: This meta-analysis was registered in PROSPERO (CRD42024519116). We searched PubMed, Embase, Cochrane Library and Web of Science for randomized controlled trials that compared adding Peg-IFN to long-term NAs with NAs alone for the treatment of CHB. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. Results: Seven trials with 692 participants were included. Compared to NAs monotherapy, sequential combination therapy significantly increased the HBsAg seroclearance rate (RR 4.37, 95%CI: 1.92–9.55; I2 = 0%) and HBsAg seroconversion rate (RR 3.98, 95%CI: 1.50–10.54; I2 = 0%), and the results reached statistical significance. Compared to NAs monotherapy, sequential combination therapy showed a significant increase in HBeAg seroclearance rate (RR 2.04; 95%CI: 0.47–8.82; I2 = 73%) and HBeAg seroconversion rate (RR 2.10; 95%CI: 0.41–10.71; I2 = 67%), but did not reach statistical significance. Sequential combination therapy was more likely to experience adverse events. Although most reactions are mild and reversible, vigilant monitoring for treatment-related adverse events is essential, with prompt intervention when needed. Conclusion: For CHB patients on long-term NAs treatment, sequential combination therapy boosts HBsAg seroclearance and HBsAg seroconversion rates compared to monotherapy. However, it may increase adverse events. Additional studies are needed to thoroughly evaluate its clinical effectiveness, given the current limited research available. Systematic Review Registration: PROSPERO, identifier CRD42024519116. [ABSTRACT FROM AUTHOR]

This study aimed to compare the serum lipid profiles between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in the long-term treatment of chronic hepatitis B (CHB). We analyzed data from treatment-naïve CHB patients administered with TDF or TAF, collected from electronic medical records between May 2017 and September 2022. Serum lipid indices, including total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL), and their ratios (TC/HDL, LDL/HDL), were assessed at baseline, and at 48 and 96 weeks. Propensity score matching (PSM) adjusted for baseline differences between groups. From 2344 patients initially screened, 418 were included for the 48-week analysis (265 on TDF, 153 on TAF) and 292 for the 96-week analysis (238 on TDF, 54 on TAF). At 48 weeks, comparing the serum lipid indicators between the pre- and post-treatment, TDF significantly reduced TC and TC/HDL, whereas TAF induced widespread dyslipidemia, characterized by elevated levels of TC, TG, LDL, LDL/HDL, and TC/HDL, and reduced HDL (P < 0.05). After PSM grouping, TAF remained significantly associated with higher TC, TG, LDL, LDL/HDL, and TC/HDL compared to TDF (P < 0.05). Over 48 weeks, TAF treatment was associated with significant increases in TC, TG, and LDL, whereas TDF treatment led to decreases (P < 0.05). TC/HDL and LDL/HDL increased in both groups, but more significant in TAF (P < 0.05). At 96 weeks, the TAF group continued to exhibit significantly higher levels of TC, LDL, and LDL/HDL compared to the TDF group (P < 0.05). Notably, LDL levels were 115.65 ± 28.07 mg/dL in TAF versus 96.07 ± 23.97 mg/dL in TDF. The increase in TC/HDL ratio in the TAF group was higher than in the TDF group, though not statistically significant. Furthermore, TAF treatment was associated with significant increases in LDL (18.58 ± 24.35 mg/dL) and LDL/HDL ratio (0.41 ± 0.95) over 96 weeks, while TDF treatment showed reductions in TC (-8.13 ± 30.86 mg/dL). Between 48 and 96 weeks, most lipid changes in the TDF group were not statistically significant, except for increases in LDL and LDL/HDL. In the TAF group, an increasing trend of LDL and TC/HDL was noted, although LDL showed a slight turnover after 48 weeks. This real-world study provides new evidence that TAF can induce dyslipidemia, while TDF exhibits a lipid-lowering effect in CHB. Patients at high risk for hepatic steatosis and cardiovascular diseases should consider these effects when choosing between TAF and TDF. [ABSTRACT FROM AUTHOR]

The article "Minimising Risks in CHB Management Guidelines: A Zero-Risk Approach" published in the Journal of Viral Hepatitis discusses the global health impact of chronic hepatitis B (CHB) infection, emphasizing the need for improved disease outcomes. It highlights the World Health Organization's goal of HBV elimination by 2030 and the challenges faced in achieving this target, especially in low- and middle-income countries. The document also delves into the immune response in chronic HBV infection, disease phases of CHB, goals of treatment, and the economic argument for expanding CHB treatment guidelines. The authors advocate for early initiation of antiviral treatment to reduce the risk of fibrosis progression and hepatocellular carcinoma development. [Extracted from the article]

Issue Addressed Methods Results Conclusions So What? This study examines Australia's Hepatitis B public health policies with a focus on the Pacific Australia Labour Mobility scheme seasonal workers as a priority population. The aim is to evaluate if Australia's Hepatitis B public health policies adequately address health disparities and equitable access to health care for seasonal workers as a priority population. We draw comparisons with the public health policies of New Zealand and Canada, to understand how these nations approach similar health concerns among their temporary seasonal workers.A health policy analysis was conducted on the public health Hepatitis B policies in Australia and then compared with those in Canada and New Zealand. Due to the nature of the study question, the review had a major focus on grey literature. The search was undertaken in two stages, including (1) Google search engine and (2) targeted websites. Basic document data was produced in descriptive summaries. Any data either explicitly or inexplicitly relating to the elimination of hepatitis B or equity towards the inclusion of seasonal workers was produced as analytical summaries through multiple revisions.Nineteen documents were identified, predominantly from Australia. Although Hepatitis B public health policies emphasised testing and awareness in priority populations, specifically mentioning seasonal workers as a priority population was absent in all three countries.The study underscores the exclusion of temporary seasonal workers in public health policies and strategies as a human rights issue, conflicting with principles of equity and equitable access to health care. Despite acknowledging challenges for temporary visa holders, policies lack specific provisions for seasonal workers. Addressing this gap is crucial for health equity and inclusive health systems.Our findings highlight the need to prioritise equity for temporary seasonal workers to achieve hepatitis B elimination goals by 2030. Exclusion from public health policies is a human rights concern, impacting access to quality health care. This study advocates for inclusive policies explicitly recognising temporary seasonal workers as a priority population, aligning with international human rights commitments to health care for all. [ABSTRACT FROM AUTHOR]

ABSTRACT The year 2024 is the year of new clinical practice and management guidelines for chronic hepatitis B virus (HBV) infection. World Health Organization (WHO) published the updated HBV guidelines in March 2024. In contrast, two key international societies for liver diseases, including the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), are currently in the process of updating their clinical practice guidelines for HBV. In 2022, China published their HBV guidelines, regarded as one of the most uncompromising ones as the threshold to start antiviral treatment is set at detectable HBV DNA above 10–20 IU/mL. In this chapter, the latest developments in the HBV guidelines with a specific focus on the Chinese & WHO guidelines are discussed. Specifically, the pros and cons of lowering treatment thresholds and the benefits of treating more people to avoid the complications of chronic hepatitis B, specifically HCC, are reviewed. [ABSTRACT FROM AUTHOR]

Chronic Hepatitis B Virus (HBV) infection remains a significant public health concern, particularly in Africa, where the burden is substantial. HBV is an enveloped virus, classified into ten phylogenetically distinct genotypes (A–J). Tests to determine HBV genotypes are based on full-genome sequencing or reverse hybridization. In practice, both approaches have limitations. Whereas diagnostic sequencing, generally using the Sanger approach, tends to focus only on the S-gene and yields little or no information on intra-patient HBV genetic diversity, reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV diagnostic sequencing protocol suitable for clinical virology that yields both complete genome sequences and extensive intra-patient HBV diversity data. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit (Oxford nanopore Technologies, Oxford, OX4 4DQ, UK), ONT GridION sequencing, genotyping using genome detective software v1.132/1.133, a recombination analysis using jpHMM (26 October 2011 version) and RDP5.61 software, and drug resistance profiling using Geno2pheno v2.0 software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 residual diagnostic samples from HBV-infected patients in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world. [ABSTRACT FROM AUTHOR]

Background: Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. Objectives: To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. Materials and methods: Forty‐eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group‐1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group‐2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty‐eight healthy male donors were included as control. The standard semen parameter analysis, real‐time polymerase chain reaction, quantitative real‐time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. Results: The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group‐1 and Group‐2 was not statistically significant. In Test Group‐2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18 × 103/mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm‐derived embryos through fertilization and retained their function in replication, transcription, and translation. Conclusion: Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer. [ABSTRACT FROM AUTHOR]

Aim: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long‐term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real‐world setting. Methods: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression. Results: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05). Conclusions: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long‐term outcomes of patients with CHB in the Japanese population. [ABSTRACT FROM AUTHOR]

Aim: An association between hepatitis B core‐related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment‐naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. Methods: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of −1 log IU/mL from baseline) were evaluated. Results: The study population comprised 241 patients, 36.9% of whom were HBeAg‐positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was −1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10−6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. Conclusions: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment. [ABSTRACT FROM AUTHOR]

Aim: Autotaxin (ATX) is a newly identified liver fibrosis biomarker; however, its clinical usefulness remains unclear. Therefore, we analyzed the changes in patients with chronic hepatitis B virus infection treated with nucleos(t)ide analogs (NAs) to evaluate its usefulness. We also investigated the predictors of hepatocellular carcinoma development, including ATX, in patients with chronic hepatitis B based on their clinical characteristics. Methods: This retrospective study included 179 patients with hepatitis B virus infection treated with NAs for >2 years. First, we measured the ATX levels before and up to 10 years after initiating entecavir (therapy for 88 patients whose serial ATX levels could be measured before and during entecavir therapy. Subsequently, for 179 patients whose ATX levels could be measured at the commencement of NAs, we examined the factors involved in developing hepatocellular carcinoma, including ATX. Results: The ATX levels showed a gradual and significant decrease during the observation period of up to 10 years. Multivariable analysis showed that a baseline ATX/upper limits of normal ratio ≥1.214, age, and alkaline phosphatase levels were independent risk factors for hepatocellular carcinoma development. The combination of age and ATX/upper limits of normal ratio was used to stratify the high‐risk groups for liver carcinogenesis. Conclusions: A decrease in ATX levels up to 10 years after the commencement of therapy suggested that ATX is a helpful biomarker in evaluating fibrosis in patients undergoing long‐term NA therapy. Furthermore, this study showed that combining age and the baseline ATX/upper limits of normal ratio may help identify high‐risk carcinogenesis groups. [ABSTRACT FROM AUTHOR]

Optimal disturbances of the periodic solution of the hepatitis B dynamics model corresponding to the chronic recurrent form of the disease are found. The dependence of the optimal disturbance on the phase of periodic solution is analyzed. Four phases of the solution are considered, they correspond to clinically different periods of development of the immune response and severity of the disease, namely, activation of antiviral immune reactions, attenuation of reactions, peak and minimum viral load. The possibility of using optimal disturbances to exit the domain of attraction of the considered periodic solution using minimal impact is studied. The components of disturbances that may underlie the phenomenon of spontaneous recovery from chronic hepatitis B observed in clinical practice are identified. [ABSTRACT FROM AUTHOR]

Background: Incidence of hepatocellular carcinoma (HCC) had been increasing steadily among older Americans but plateaued in 2015–2017. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are important causes of HCC. The impact of improved treatments for these infections on recent trends in HCC incidence is unclear. Aims: To examine the relationship between use of antiviral therapy for chronic viral hepatis and HCC incidence in older Americans. Methods: We used 2007–2017 data from the Surveillance, Epidemiology, and End Results—Medicare database to estimate age-standardized incidence rates and average annual percent changes (AAPCs) for viral hepatitis-attributable HCC among individuals ≥66 years. We analyzed data from Medicare Part D to determine the frequency of HBV and HCV treatment utilization in this population. Results: Overall HCC incidence increased 10.5%, from 22.2/100,000 in 2007 to 24.5/100,000 in 2017 (AAPC, 1.3%). During that time, HBV-attributable HCC rates decreased from 2.5 to 2.0/100,000 (AAPC, -1.6%), while HCV-attributable HCC rose from 6.6 to 8.0/100,000 (AAPC, 2.0%). HBV treatment among patients with HBV infection increased by 66% (2007, 7.4%; 2015, 12.3%). Treatment for HCV was stable at <2% during 2006–2013 but rose to 6.9% in 2014 and 12.7% in 2015, coinciding with the introduction of direct acting antiviral agents for HCV. Conclusions: A decreased incidence of HBV-attributable HCC corresponded with an increased uptake in treatment for that infection. Despite a marked increase in the effectiveness and frequency of HCV treatment in 2014 and 2015, HCV-attributable HCC had not begun to fall as of 2017. [ABSTRACT FROM AUTHOR]

Objective: To compare the therapeutic efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with chronic Hepatitis-B (CHB). Methods: This retrospective study included 110 patients with CHB who received treatment at The First People's Hospital of Linping District, Hangzhou from January 2021 to January 2023. Clinical data of the patients were reviewed and the patients were classified according to the treatment received: TDF group (n=53, patients received TDF treatment) and ETV group (n=57, patients received ETV treatment). Hepatitis-B virus deoxyribonucleic acid (HBV DNA) levels, liver function indicators, hepatitis-B e antigen (HBeAg) seroconversion rate, alanine transaminase (ALT) normalization rate, HBV DNA negative conversion rate, overall efficacy, and incidence of adverse reactions were compared. Results: The total efficacy of the treatment in the TDF group was 94.33%, significantly higher than that in the ETV group (78.95%; P<0.05). After the treatment, the HBV DNA levels in both groups decreased compared to pretreatment levels, and were significantly lower in the TDF group compared to the ETV group (P<0.05). Both groups showed significant post-treatment improvement in liver function that was markedly better in the TDF group compared to the ETV group (P<0.05). The HBeAg seroconversion rate, ALT normalization rate, and HBV DNA conversion rate in the TDF group were significantly higher compared to the ETV group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups. Conclusions: Compared with ETV, TDF has comparable adverse reaction profile but has more significant clinical effects in patients with CHB, improving HBeAg seroconversion rate, ALT normalization rate, and HBV DNA negative conversion rate. TDF is associated with lower HBV DNA levels after treatment and better improvements in liver function of patients. [ABSTRACT FROM AUTHOR]

An integral component to achieving worldwide chronic hepatitis B (CHB) elimination is addressing vertical transmission. Guidelines differ in their recommendations for breastfeeding while on tenofovir disoproxil fumarate (TDF). To conduct a systematic review of published studies analysing the concentration of tenofovir (TFV) in the breast milk of mothers receiving TDF and determining infant exposure from breastfeeding. We conducted a systematic literature search of studies evaluating infant safety from the breast milk of breastfeeding mothers receiving TDF for any indication that reported a TFV breast milk concentration. Daily infant exposure was used to calculate the relative dose of TFV in infants. Other pertinent information collected was the concentration of TFV in maternal and infant plasma, the duration of therapy of TDF and the indication for TDF. We identified 10 studies including 443 patients—266 of whom were mothers, and the remaining were infants—that reported the TFV concentration of breast milk in breastfeeding mothers receiving TDF. A total of 654 breast milk samples were included. The mean TFV concentration from all the studies that reported a median concentration of TFV was 4.8 ng/mL (95% CI [3.8, 5.8]). The mean infant exposure of TFV from breast milk was 0.56 μg/kg/day (95% CI [0.44, 0.68]). The mean relative dose was determined to be 0.01% of the weight‐based recommended infant dose. Infant plasma levels of TFV were also collected. This was undetectable in a majority of the studies that reported it. Based on the negligible infant exposure of TFV while breastfeeding, from a pharmacologic and toxicity standpoint, maternal dosing of TDF appears safe for breastfeeding infants. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) is the leading cause of hepatocellular carcinoma (HCC) globally. We described and evaluated the outcomes of patients with CHB‐HCC in Canada. In this retrospective cross‐sectional cohort study, data were analysed from CHB mono‐infected subjects seen between 1 January 2012 and 31 December 2022, and entered the Canadian Hepatitis B Network Registry. Descriptive analysis and chi‐squared modelling were used to compare cohorts, followed by multivariable survival analysis regarding survival post‐diagnosis. Statistical analyses were completed in R version 2.2. Of the 6711 patients with CHB who met inclusion criteria, 232 (3.5%) developed HCC. Compared with the CHB cohort, the majority of CHB‐HCC cohort were male, SEA and HBeAg negative and born in endemic area (80% vs. 56%, 73% vs. 55%, 84% vs. 54%, 64% vs. 40% and all p < 0001). Overall, median HBV DNA level was log 2.54 (IQR: 0–4.04). Advanced liver disease, defined as minimum Fibrosis stage F3, was seen in 9.4% of overall cohort, but 92% of HCC cohort. At diagnosis, median tumour size was 2.5 cm (IQR: 1.7–4.0) and mean tumour number was 1.33 (SD: 1.33), with 81% of patients BCLC 0‐A. Fifty‐three per cent of patients were diagnosed with HCC as part of surveillance protocols. The survival rate after HCC diagnosis was 78.7%, during the median follow‐up of 52.9 months (IQR: 17–90). In multivariable analysis, survival was significantly correlated with diagnosis through the screening programme. In this large cohort of patients with CHB‐HCC, the majority of patients were detected with early‐stage HCC and received treatment with curative intent, resulting in strong survival rates. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a global issue and can lead to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg) is an important marker of HBV infection and HBsAg quantification could be a useful tool in clinical practice. This systematic literature review aimed to explore the association between HBsAg titres and long‐term disease outcomes and evaluate the relationship between HBsAg titres, or changes in HBsAg titres, and clinical and treatment characteristics in patients with chronic HBV infection. Structured searches were performed in MEDLINE and Embase (January 2000 to 31 March 2023). Eighty‐two studies were included, comprising 51% retrospective cohort studies, mostly conducted in Asia (85%). HBsAg levels were shown to predict the long‐term development of cirrhosis and HCC in patients who were untreated prior to and during follow‐up; however, these data were inconclusive in mixed and treated populations. HBsAg titres were significantly associated with various virological markers including serum HBV DNA, HBcrAg, HBeAg, HBV RNA levels, intrahepatic covalently closed circular DNA (cccDNA) and intrahepatic HBsAg expression. HBsAg titres generally declined over time; this decline was more pronounced in early (HBeAg‐positive) than later disease phases (HBeAg‐negative). Higher decline in HBsAg levels was consistently associated with subsequent HBsAg seroclearance and a greater decline in total intrahepatic HBV DNA and cccDNA levels. In conclusion, this review showed that HBsAg levels and rates of decline could inform assessment, management and prediction of outcomes in chronic HBV infection. Further studies in broader, more diverse populations and treated patients are needed. [ABSTRACT FROM AUTHOR]

To explore the value of ultrasound elastography combined with serological indicators in the diagnosis of liver fibrosis in chronic hepatitis B. A total of 156 patients with chronic hepatitis B from April 2020 to February 2022 were enrolled in this study as subjects. They were assigned to the liver fibrosis group (n=115) and the non-liver fibrosis group (n=41) according to whether the patients had liver fibrosis. They were divided into S1 stage (n=48), S2 stage (n=38), and S3 stage (n=29) according to histopathological staging criteria. Shear wave elastography (SWE) values, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen type III (PCIII), and laminin (LN) were compared among patients in each stage. Spearman's method was utilized to analyze the correlation of liver serum biochemical indicators and SWE value with liver fibrosis. The predictive performance of SWE value and serological indicators was analyzed using receiver operating characteristic curves. According to Spearman's method, the liver fibrosis stage was positively correlated with SWE value. Serological indicators combined with ultrasound elastography can accurately assess the degree of liver fibrosis in patients with chronic hepatitis B and provide a basis for clinical judgment. [ABSTRACT FROM AUTHOR]

The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants noninvasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in 10 medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from SHAP (Shapley Additive exPlanations), were compared with Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index using the area under receiver-operating characteristic curve (AUROC) and decision curve analysis (DCA). Of 1,198 eligible patients, the random forest model achieved AUROCs of 0.778 (95% confidence interval [CI], 0.749–0.807) for diagnosing advanced fibrosis (random forest advanced fibrosis model) and 0.777 (95% CI, 0.748–0.806) for diagnosing cirrhosis (random forest cirrhosis model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the random forest advanced fibrosis model obtained an AUROC of 0.825 (95% CI, 0.787–0.862) in patients with hepatitis B virus DNA ≥105 IU/mL, and the random forest cirrhosis model had an AUROC of 0.828 (95% CI, 0.774–0.883) in female patients. The 2 models outperformed Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index in the training cohort, and also performed well in the validation cohort. The random forest models provide reliable, noninvasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the comanagement of the 2 diseases. ClinicalTrials.gov, Number: NCT05766449. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) and nucleotide analogues [entecavir (ETV) and tenofovir disoproxil fumarate (TDF)] used in its treatment have been shown to affect metabolic parameters in many studies. In this study, we aimed to investigate the effects of metabolic events associated with CHB and nucleotide analogues (NAs) used in CHB treatment on ischemic heart diseases (IHD) and cardiovascular diseases (CVD). Methods: This retrospective study was conducted between June 2022 and January 2024 with a total of 241 patients diagnosed with non-cirrhotic CHB in the gastroenterology outpatient clinic, 96 of whom did not receive hepatitis B treatment, 110 of whom received TDF, and 35 of whom received ETV treatment. Patients were evaluated in terms of metabolic, CVD, and hepatology depending on whether they received antiviral treatment or not. In our study, the triglyceride)glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) were calculated in patients to evaluate potential risk factors for CVD. Again, while the total cholesterol-to-HDL-C ratio (TC/HDL-C), which is associated with CVD\IHD, was evaluated, the ‘4-factor fibrosis index’ (FIB-4) score, which is a non-invasive indicator of liver fibrosis, was also evaluated. Results: Diabetes mellitus (DM), fasting blood sugar (FBS), oral antidiabetic drug (OAD) usage rate, and insulin usage rate were high in patients receiving ETV treatment. The TyG index of patients receiving ETV was higher than patients in the other group (p = 0.035; p<0.05). It was determined that the probability of detecting ETV treatment in patients with a TG/HDL-C ratio of ≥1.82 cut-off value was 4.250 times higher. The odds ratio for TG/HDL-C measurements was 4.250 (95% CI: 1.384–13.054). FIB-4 score, which is a non-invasive indicator of liver fibrosis, was found to be higher in patients receiving ETV than in other groups. Conclusion: In patients with CHB, a relationship was observed between markers used to predict CVD risk, such as the TyG index and TG/HDL-C ratio. The group with high levels of these two markers and a high potential for developing CVD was patients receiving ETV treatment. In this first study in the literature showing the relationship between CHB and CVD, we found that the relative risk of CVD was increased in patients using ETV. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies. Methods: The Nano-Glo® HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model. Results: Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg. Conclusions: Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent. [ABSTRACT FROM AUTHOR]

Background: Fatty acid binding protein 1 (FABP1), a low molecular weight intracellular protein, has been proposed as a potential useful serum biomarker for liver injury. However, limited investigations have been conducted in chronic hepatitis B virus (HBV)-related liver disease. Objective: To investigate the diagnostic potential of FABP1 in disease progression among patients with chronic HBV-related liver disease. Methods: A prospective study was conducted on 293 patients with chronic HBV-related liver diseases, including chronic asymptomatic carrier (ASC), chronic hepatitis B (CHB). FABP1 was measured in serum samples collected at admission and some selected liver biopsies. Results: Immunohistochemical analysis revealed abundant cytoplasmic expression of FABP1 in hepatocytes. A significant negative correlation was observed between FABP1 expression and inflammation grades in liver tissue (Spearman's r = -0.355, P = 0.017). However, no statistically significant correlation was found with fibrosis (P > 0.05). Serum FABP1 levels in the case group were significantly higher than in the healthy control (HC) group [median: 804.2 (687.8, 939.2) vs. 709.1 (626.2, 807.8) ng/ml, Z = -5.505, P < 0.001] and showed correlations with alanine aminotransferase (ALT), aspartate aminotransferase (AST); total bilirubin (TBIL); direct bilirubin (DBIL); albumin (ALB), etc. Its levels progressively increased with the advancement from ASC to CHB, with significant differences compared to the HC group (P < 0.001), especially in ASC patients with high HBV DNA (exceeding 106 IU/ml, P = 0.019), HBeAg positive (P = 0.013) and ALT higher than 0.5 times upper limit of normal (ULN)(P = 0.035). Meanwhile, serum FABP1 in CHB patients with higher TBIL(P = 0.005) or the severe CHB were higher (P = 0.002). Conclusion: Our study demonstrated a significant inverse correlation between FABP1 levels and the severity of inflammation grades in patients with HBV-related liver diseases. Furthermore, elevated serum FABP1 levels were observed in these patients, suggesting its potential as a biomarker for assessing HBV-related liver damage to initiate antiviral therapy. Additionally, further evaluation is required to determine its potential as a biomarker for assessing disease severity. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) leads to liver inflammation and dysfunction, resulting in liver fibrosis and cancer. Nucleos(t)ide analogues (NAs), inhibitors of hepatitis B virus (HBV), specifically suppress HBV replication. We proposed that immune modulation benefits seroconversion by HBsAg loss. However, activation of T lymphocytes also deteriorates hepatic inflammation. Therefore, we intended to investigate the T cell status and its relationship with hepatic functions in CHB patients treated with NAs. Serum markers, including liver function markers AST, ALT, and HBV-infected markers HBV DNA, HBsAg, HBeAg, and HBsAb were measured in the clinical routine. The T cell levels and markers, including CD69, CD107a, CXCR3, and PD-1 were investigated using flow cytometry. Meanwhile, IFNγ, IL-2, and CXCL10 as immune activation markers in the PBMCs were investigated using qPCR. To validate the effects of NAs on T cell status, qPCR and flow cytometry were used to investigate the gene expression in the HepG2 and PLC5 cells treated with NAs, and in the healthy PBMCs treated with the cell-cultured supernatant. We found that NAs significantly suppressed HBV DNA and reduced AST and ALT levels in the CHB patients. Meanwhile, AST and ALT were both positively correlated with activation marker CD107a in CD8+ T cells. In addition, we found that the CHB patients with seroconversion exhibited a higher CD4/CD8 ratio (p < 0.05) compared to non-seroconversion. We demonstrated that NAs potentially induced IFNs and PD-L1 expression in HepG2 and PLC5 cells. Moreover, the collected supernatant from NAs-treated HepG2 significantly activated PBMCs. This study revealed that the reduction of HBV by NAs may be the reason leading to less AST and ALT levels. We further demonstrated that NAs induced IFN expression in hepatic cells to potentially activate T lymphocytes, which was positively associated with AST and ALT levels in the CHB patients. The results may explain the phenomena in clinical that when the virus is reactivated by aborted use of NAs, it causes consequent T cells-mediated severe acute-on-chronic liver injury. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Several studies have reported that chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels (100 or 10 IU/mL) at the cessation of nucleot(s)ide analogs (NA) have a favorable prognosis. In this retrospective study, we evaluated the duration of NA treatment and the factors associated with achieving these low HBsAg levels. We also examined the relationship between HBsAg and hepatitis B core‐related antigen (HBcrAg) levels at the time of NA discontinuation and subsequent clinical outcomes.This study included 153 CHB patients who initiated NA therapy at our hospital, received treatment, and were followed up for over 1 year.The cumulative incidence rates of achieving low HBsAg levels at 5 and 10 years post‐NA administration were as follows: 19.0% and 29.2% for HBsAg <100 IU/mL, 13.8% and 17.6% for HBsAg <10 IU/mL, and 9.5% and 13.5% for HBsAg <0.05 IU/mL, respectively. Hepatitis B virus genotypes other than genotype C (hazard ratio [HR] 3.47; p < 0.001) and an HBsAg level <1000 IU/mL at the start of NA therapy (HR 2.49; p = 0.008) were significantly associated with achieving HBsAg levels <100 IU/mL. Among 27 patients who discontinued NA therapy, 5 patients with HBsAg levels <100 IU/mL and HBcrAg levels <3 log U/mL at the time of discontinuation did not experience virological relapse.The cumulative rates of achieving HBsAg levels <100 IU/mL were relatively high. Discontinuation of NA may be considered based on HBsAg and HBcrAg levels during the course of NA therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the features of HBV-specific T cell reactivity across the pregnant, postpartum or non-pregnant women with chronic HBV infection. Methods: A total of 283 patients with chronic HBV infection were enrolled in this study, including 129 patients during pregnancy, 58 patients during postpartum less than 6 months and 96 non-pregnant patients at childbearing age. A universal ELISpot assay was set up using a broad-spectrum T-cell epitope peptide library which containing 103 functionally validated CD8+ T-cell epitopes derived from overall HBsAg, HBc/eAg, HBx and HBpol proteins and fitting to the human leukocyte antigen polymorphisms of Chinese population. Then, The functional HBV-specific T cells in peripheral blood were detected. Results: The spot-forming units (SFUs) of HBV-specific T cells in the pregnant group showed no statistical difference from the postpartum group, but significantly less than that in the non-pregnant group (p = 0.046). In the untreated patients, the pregnant group displayed HBe/cAg-specific T cells (SFUs) less than the non-pregnant group (P = 0.025) and the postpartum group (P = 0.045). Meanwhile, in the NUCs-treated patients, the three groups presented similar HBV-specific T cell reactivity. Furthermore, the SFUs in the NUCs-treated pregnant group were similar to that in the NUCs-untreated pregnant group. Importantly, ROC analysis demonstrated that the HBV-specific T cells (SFUs) (AUC = 0.742) and combined with HBsAg levels (AUC = 0.775) or with HBeAg level (AUC = 0.78) had a good predictive performance for hepatitis progression during pregnancy group. Conclusion: Pregnancy can reduce HBV-specific T cell reactivity in the women with chronic HBV infection, and NUCs treatment cannot improve their HBVspecific T cells reactivity. Routine monitoring of HBV-specific T cells during pregnant and postpartum period can provide precise evaluation for immune function and valuable guidance for treatments. [ABSTRACT FROM AUTHOR]

The document discusses the use of blinatumomab in patients with CD19 positive B-ALL and hepatic dysfunction. Blinatumomab, a bispecific monoclonal antibody, has shown favorable survival benefits in B-ALL patients, especially those who cannot tolerate conventional chemotherapy. The document presents three cases where blinatumomab was used in patients with hepatic dysfunction, showing varying outcomes and highlighting the need for further research to confirm its safety and efficacy in this patient population. [Extracted from the article]

Introduction: Patients with chronic HBV infection (CHI) exhibit defective antiviral immune-response whose underlying causes still remain unclear. Monocytes act as immune sentinels for pathogens and can regulate immunity via interaction with other immune-cells, apart from differentiating into macrophages. Immunecheckpoint molecules (ICMs) expressed by immune-cells, including monocytes are known to negatively regulate immune-responses. Here, we evaluated the expression of ICMs, namely, Gal-9, PD-L1, and CTLA-4 on monocytes in different phases of CHI, identified the viral and the host factors causing their aberrant expression and investigated their impact during interaction of monocytes with Tcells, B-cells and NK-cells and also on monocyte to macrophage differentiation. Influence of Tenofovir therapy on the expression of monocytic ICMs was also studied. Methods: Collection of blood and liver-tissue samples from HBV infected patients and controls, flow-cytometry, cell sorting, cell culture and immunefluorescence were performed for this study. Results: Gal-9+ and PD-L1+-monocytes were significantly increased in HBeAgpositive as well as HBeAg-negative chronic hepatitis B (CHB) patients than healthy controls (HC). In immune-tolerant (IT) subjects, only Gal-9+- monocytes and in inactive carriers (IC), PD-L1+-monocytes were higher than HC while CTLA-4+-monocytes remained comparable among groups. High serum Hepatitis B surface antigen (HBsAg) concentration in CHB as well as IT and TNF-α in CHB triggered monocytic Gal-9-expression whereas, PD-L1 was induced by elevated TNF-α and IL-4 in CHB and IL-1β in CHB and IC. Purified monocytes from CHB and IT having high Gal-9 expression led to expansion of CD4+CD25+FOXP3+-Tregs, CD19+IL-10+-Bregs and CD19+CD27-CD21- atypical memory B-cells and these monocytes also preferentially differentiated into M2-macrophages. These phenomena were reversed by anti-Gal-9- antibody. Parallelly, PD-L1+-monocytes in CHB and IC reduced IL-2/IFN-γ and IL-6 production by HBV-specific T- and B-cells respectively, which were restored by anti-PD-L1-antibody. Both Gal-9+- and PD-L1+ -monocytes caused decline in IFN-γ+-NK-cells but enhanced IL-10-expressing HBVspecific-T-cells and NK-cells. Increased intrahepatic CD14+Gal-9+ and CD14+PD-L1+-monocytes were noted in CHB patients than HC. One-year tenofovir therapy failed to reduce monocytic Gal-9 and PD-L1 along with the levels of HBsAg, TNF-α, IL-1β and IL-4. Conclusions: Monocytic Gal-9 and PD-L1, expressed heterogeneously in different phases of CHI, exert diverse inhibitory effects on immune-responses and their therapeutic targeting could boost anti-HBV immunity. [ABSTRACT FROM AUTHOR]

Aim: An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 − 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC). Patients and methods: Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Results: The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively). Conclusion: The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis. [ABSTRACT FROM AUTHOR]

ABSTRACT International guidelines suggest cessation of nucleos(t)ide analogues (NA) independent of HBsAg loss in HBeAg‐negative patients after 2–3 years of viral suppression. Detectable HBV‐RNA levels at the time of NA cessation were linked to a better prediction of relapse after NA withdrawal in small cohorts of HBeAg‐negative patients. This study proves the impact of HBV‐RNA levels in the prediction of relapse in a large cohort of HBeAg‐negative patients, mainly infected with genotype B or C. Serum levels of HBV‐RNA, HBsAg, anti‐HBc and HBcrAg were determined before NA withdrawal in 154 HBeAg‐negative patients, participating either in a therapeutic vaccination trial (NCT02249988) or in an observational register trial (NCT03643172). Importantly, vaccination showed no impact on relapse. Endpoints of the study were virological relapse (HBV‐DNA > 2000 IU/mL) or biochemical relapse (attendant ALT levels ≥ 2 × ULN) 24 weeks after NA cessation. Virological relapse occurred in 54.5% of patients (N = 84/154), including eight patients (10%) developing an ALT flare. Baseline HBV‐RNA level did not differ significantly between relapsers and off‐treatment responders (p = 0.92). No significant difference occurred in proportions of detectable HBV‐RNA levels between off‐treatment responders (N = 27/70; 38.6%) and relapsers (N = 31/84; 36.9%) (p = 0.99). Combining predefined HBsAg cut‐offs (100 IU/mL, p = 0.0013), anti‐HBc cut‐offs (325 IU/mL, p = 0.0117) or HBcrAg cut‐offs (2 log U/mL, p = 0.66) with undetectable HBV‐RNA (HBsAg, p = 0.0057; anti‐HBc, p = 0.085; HBcrAg, p = 0.60) did not improve relapse prediction. The value of HBV‐RNA levels at timepoint of NA cessation for the prediction of relapse is limited in HBeAg‐negative patients.Trial Registration: ABX 203‐002: NCT02249988; Terminator 2: NCT03643172 [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aims Methods Results Conclusion Achieving HBsAg loss is a critical clinical milestone in the management of chronic hepatitis B (CHB) towards the eradication of hepatitis B. However, there are limited researches on the incidence and determinants of HBsAg loss in paediatric CHB patients undergoing antiviral treatment. Therefore, we aimed to analyse the incidence and potential determinants of HBsAg loss in children who suffered from CHB and received antiviral treatment.This retrospective cohort study was performed on paediatric patients with progressive CHB who initiated either monotherapy or combination therapy using interferon/peg‐interferon and entecavir. We utilised Cox regression models to evaluate the relationships between HBsAg loss and various determining factors.In total of 306 subjects with an average age of 4.99 years (range 1–15) were identified in this study, of whom 200 (65.4%) were male. After a median follow‐up of 26 months, HBsAg loss occurred in 135 participants. The accumulated rate of HBsAg loss was 67.8% at the end of the follow‐up evaluation. Multivariate Cox regression analysis revealed that older age (HR = 0.84, 95% CI: 0.79–0.90), female sex (HR = 1.61, 95% CI: 1.13–2.30), baseline HBsAg levels (HR = 0.72, 95% CI: 0.62–0.84), HBsAb positivity (HR = 1.77, 95% CI: 1.20–2.59) and serum bilirubin levels (HR = 0.96, 95% CI: 0.92–0.99) were statistically significant predictors of HBsAg loss.The incidence of HBsAg loss continues to increase in paediatric patients with CHB after antiviral treatment. Age, sex, baseline HBsAg and bilirubin levels and HBsAb positivity are found to be associated with sustained HBsAg loss. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent hepatitis B virus (HBV) mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the 2 regimens are lacking. Design In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to 31 March 2024 and extracted data from cohort studies and randomized controlled trials (RCTs) in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. Results We included 31 studies with 2588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6–12 months (risk ratio: 0.10, 95% confidence interval [CI].07–.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval.16–7.61). Network meta-analysis showed equal efficacy of the 2 regimens in reducing MTCT (risk ratio: 1.09, 95% CI.15–7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking:.77 vs.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. Conclusions Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers. [ABSTRACT FROM AUTHOR]

ABSTRACT Estimates of chronic hepatitis B virus (HBV) prevalence and critically the amount of infection that is undiagnosed or unlinked to care are uncertain—even in countries like UK where vertical transmission and overall prevalence are very low. In the absence of country of birth data, we aim to estimate HBV prevalence through combining public health surveillance data on antenatally screened women by ethnic group and multipliers generated from non‐antenatally screened populations by ethnic group with English population denominators. Of 714,287 women aged 16–49 years with ethnic group data tested as part of antenatal care between 2015 and 2021, 4174 (0.6%) were HBsAg‐positive; 94% in people of ethnic groups other than White British. Of 1,447,467 people tested for HBsAg with ethnic group data from other testing sources (primary and secondary care excluding occupational health and renal services), 27,628 (1.9%) were HBsAg‐positive; 87% in people of ethnic groups other than White British. We estimate that the overall number and prevalence of people with chronic hepatitis B in England is 268,767 (95% CI: 227,896–314,044) and 0.58% (95% CI: 0.50–0.68). Approximately two‐thirds were male, one‐third female, and 68% were aged under 50. We estimate that over 83% of HBV infections are in people of ethnic groups other than White British, with 23% in people from Black ethnic groups, 21% from other White ethnic groups and 19% in Asian ethnic groups. These estimates are the first step towards establishing whether England can meet World Health Organisation targets to eliminate HBV as a public health problem—using methods that can also be used by other countries. [ABSTRACT FROM AUTHOR]

Background: The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. Methods: We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). Results: A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. Conclusion: This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed. [ABSTRACT FROM AUTHOR]

Hepatitis B and C are chronic viral diseases that have a devastating impact on liver function. Though the past literature has highlighted the psychological burden of disease linked with these conditions including a high prevalence of depression and anxiety, there continues to a considerable gap in the literature regarding the broad-spectrum cross cutting psychiatric comorbidities such as mania, anger, somatic symptoms, memory disturbances, substance abuse, dissociation etc. and how they impact quality of life in those affected with these conditions. The current study used a cross sectional correlational research design with a sample of 400 participants (196 with CHB and 204 with CHC) with the mean age of 40.8 years. DSM V Cross Cutting Symptoms Measure, WHO QoL Bref, Immune Status Questionnaire and Health and Lifestyle Scale were used for data collection. The results showed a high prevalence of depression, somatic distress, anxiety, anger, memory disturbances and other associated psychiatric symptoms. Moreover, the cross cutting psychiatric symptoms (such as depression, anger, mania, anxiety, somatic symptoms, suicidal ideation, psychosis, sleep problems, memory disturbances, repetitive thoughts, dissociation, personality functioning and substance abuse had significant negative associations with quality of life, social support and resilience and their subscales. Additionally, the study found a buffering and significant mediating indirect effect of social support and resilience on the association between depression, anger, mania, anxiety, somatic symptoms, suicidal ideation, psychosis, substance abuse and perceived immune status. The results of the study point towards a high burden of disease associated with the high prevalence of cross cutting psychiatric symptoms and the need to provide different healthcare counselling and support services for those diagnosed with Hepatitis B and C. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters. Methods: We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis. Results: Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients. Conclusions: A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group. [ABSTRACT FROM AUTHOR]

ABSTRACT Low‐level viraemia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aimed to investigate the impact of different LLV types on fibrosis regression. The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P‐I‐R system. Patients were grouped as the SVR (HBV DNA < 20 IU/mL persistently) or LLV (HBV DNA between 20 and 2000 IU/mL), which were further grouped as very low‐level viraemia (VLLV, HBV DNA < 50 IU/mL), occasionally LLV (OLLV, HBV DNA ≥ 50 IU/mL only once) and multiple LLV (MLLV, HBV DNA ≥ 50 IU/mL more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). The analysis included 111 CHB patients. In the SVR group (n = 54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p = 0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients) and MLLV (10 patients) were 70.0%, 52.9% and 30.0%, respectively. Compared with SVR, VLLV (aOR = 0.78; 95% CI: 0.28–2.21; p = 0.644) was not associated with fibrosis regression, but patients with non‐VLLV (aOR = 0.27; 95% CI: 0.09–0.85; p = 0.025), especially with MLLV (aOR = 0.19; 95% CI: 0.04–0.97; p = 0.046) is significantly associated with hindered fibrosis regression. Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once.Trial Registration: ClinicalTrials.gov identifiers NCT01938781 and NCT01938820 [ABSTRACT FROM AUTHOR]

Background Timely treatment of chronic hepatitis B (CHB) reduces risks of cirrhosis and hepatocellular carcinoma. Gaps in timely treatment persist, especially among underserved safety-net populations. We aim to evaluate gaps and disparities in CHB treatment in the United States. Methods Adults with treatment-naive CHB without human immunodeficiency virus were identified from 2010 to 2018 across 3 safety-net health systems. CHB treatment eligibility was assessed using American Association for the Study of Liver Diseases (AASLD) criteria and alternative criteria, including the Simplified Approach for Hepatitis B Algorithm. Differences in CHB treatment between groups were evaluated using χ2 methods, adjusted Kaplan-Meier methods, and adjusted Cox proportional hazards models. Results Among 3749 patients with treatment-naive CHB (51.5% women, 38.7% White, 33.7% African American, 19.6% Asian, 24.6% cirrhosis), 30.0% were AASLD treatment eligible, among whom 31.0% were treated. Men were more likely than women to be treated (33.5% vs 26.6%, P <.01). On multivariable regression, there remained a trend toward greater treatment in men versus women (adjusted hazard ratio [aHR], 1.21 [95% confidence interval {CI},.96–1.54]). Disparities by race/ethnicity and insurance status were observed. When exploring outcomes using SABA criteria, similar trends were observed. Among treatment-eligible patients, greater likelihood of treatment was observed in men versus women (aHR, 1.40 [95% CI, 1.14–1.70]) and in Asians versus Whites (aHR, 1.50 [95% CI, 1.16–1.94]). Conclusions Among an ethnically diverse multicenter safety-net cohort of CHB patients, less than one-third of treatment-eligible patients received antiviral treatment. Significant disparities in CHB treatment were observed by sociodemographic characteristics. [ABSTRACT FROM AUTHOR]

Background: Viral hepatitis is the most prevalent liver disease in the world. This disease imposes a great economic burden on families and the health system. This study was conducted to investigate the economic burden of hepatitis B at different ages of the disease using a systematic review method. Methods: Using the systematic review method, the researcher extracted articles related to the economic burden of hepatitis B at different stages of the disease using domestic and international databases including SID, MEDLINE/PubMed, Embase, Web of Science, NHS Economic Evaluation Database (EED), EconLit, and Google Scholar before April 2020 and used the PICOTS framework to select the inclusion criteria. Quality assessment of methodology of the studies was evaluated using Drummond's checklist. Results: After searching for articles based on inclusion and exclusion criteria, 18 articles were included in the final analysis. The findings showed that the highest mean direct medical costs were $ 2748 for chronic hepatitis B, $ 18903 for compensated cirrhosis, $35668 for decompensated cirrhosis, and $93228 for liver cancer. In all of the studies, the highest mean direct medical costs were those of liver transplantation ($ 355000). Conclusions: The treatment costs of diseases related to chronic hepatitis B increase significantly at different stages the disease progression. Although vaccination actions can reduce the disease, we require more investment in the health system infrastructure to provide patients' access to hepatitis drugs and reduce their direct payments. [ABSTRACT FROM AUTHOR]

Case Presentation: This case report documents a unique presentation of hepatic encephalopathy induced by the reactivation of chronic hepatitis B due to Cytomegalovirus (CMV) infection in a 76-year-old female patient. The patient was admitted with a diminished level of consciousness subsequent to a week of anorexia, intermittent fever, chills, postprandial nausea, and vomiting. Laboratory tests revealed significant hepatocellular injury, while imaging suggested cirrhosis. The presence of hepatitis B surface antigen and a detectable hepatitis B virus DNA qualitative analysis was noted, alongside an elevated CMV viral load, indicating the reactivation of chronic hepatitis due to CMV infection. Therapeutic interventions included Ganciclovir for CMV infection, Colistin for an Enterococcus urinary infection, and Tenofovir for hepatitis. Upon stabilization, the patient was discharged for continued medical management. Conclusion: This case highlighted the significance of considering the reactivation of chronic viral hepatitis in the differential diagnosis of hepatic encephalopathy. It underscored the critical role of comprehensive diagnostic investigation in patients presenting with reduced consciousness, especially those with a history of liver disease. Moreover, it emphasized the importance of managing concurrent infections in the context of liver disease and served as a reminder of the potential for CMV to reactivate chronic hepatitis, leading to serious complications, such as hepatic encephalopathy. [ABSTRACT FROM AUTHOR]

Co‐existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non‐invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN‐γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p <.01), higher HBV S diversity (p =.02) and greater frequency of HBV variants associated with host‐anti‐viral immune escape. Pro‐inflammatory cytokine levels and HBV‐specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low‐level viraemia. [ABSTRACT FROM AUTHOR]

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non‐US‐born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B‐related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B‐related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings. [ABSTRACT FROM AUTHOR]

Objectives: CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA‐DR+CD8+ T cells, or bystander‐activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA‐DR+CD8+ T cell‐mediated pathogenesis during liver cirrhosis. Methods: The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity‐related indicators of CD38+HLA‐DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA‐DR+CD8+ T‐cell killing was detected using cytotoxicity and antibody‐blocking assays. Results: The proportion of CD38+HLA‐DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate‐like functional characteristics. This CD8+ T‐cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity‐related cytokines, granzyme B and perforin. IL‐15 promoted CD38+HLA‐DR+CD8+ T‐cell activation and proliferation, inducing significant TCR‐independent cytotoxicity mediated through NKG2D. Conclusions: CD38+HLA‐DR+CD8+ T cells correlated with cirrhosis‐related liver injury and contributed to liver damage by signalling through NKG2D in a TCR‐independent manner. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a common cause of acute hepatitis, with increasing incidence in Europe, including Romania. Concurrently, Romania has a high prevalence of chronic hepatitis B (CHB). There is limited research on the clinical presentation and outcomes of HEV infection in patients with pre-existing chronic hepatitis B (CHB), especially in resource-rich settings. Most literature data come from South, East, and Southeast Asia. A review of the literature on HEV and HBV co-infection indicates a severe prognosis, particularly in patients with underlying liver disease. However, the cases in this study, which did not display cirrhosis, showed varied outcomes. The role of anti-HBV treatment in improving prognosis remains uncertain and warrants further investigation. Acute HEV infection superimposed on chronic HBV infection poses significant clinical challenges, with outcomes ranging from full recovery to fatality. Preventive measures, including sanitation and vaccination against HBV, are crucial. More studies are needed to establish effective treatment protocols for this co-infection. In this study, we will analyze the clinical setting, diagnosis, particularities, and outcomes of five such cases of dual hepatotropic viral infection recorded over a period of 6 years (2018–2023) at a large Infectious Diseases clinic in Bucharest, Romania. [ABSTRACT FROM AUTHOR]

Issue Addressed: In 2014 the 'Hep B Story App', the first hepatitis B educational app in an Aboriginal language was released. Subsequently, in 2018, it was assessed and adapted before translation into an additional 10 Aboriginal languages. The translation process developed iteratively into a model that may be applied when creating any health resource in Aboriginal languages. Methods: The adaptation and translation of the 'Hep B Story' followed a tailored participatory action research (PAR) process involving crucial steps such as extensive community consultation, adaptation of the original material, forward and back translation of the script, content accuracy verification, voiceover recording, and thorough review before the publication of the new version. Results: Iterative PAR cycles shaped the translation process, leading to a refined model applicable to creating health resources in any Aboriginal language. The community‐wide consultation yielded widespread chronic hepatitis B education, prompting participants to share the story within their families, advocating for hepatitis B check‐ups. The project offered numerous insights and lessons, such as the significance of allocating sufficient time and resources to undertake the process. Additionally, it highlighted the importance of implementing flexible work arrangements and eliminating barriers to work for the translators. Conclusions: Through our extensive work across the Northern Territory, we produced an educational tool for Aboriginal people in their preferred languages and developed a translation model to create resources for different cultural and linguistic groups. So What?: This translation model provides a rigorous, transferable method for creating accurate health resources for culturally and linguistically diverse populations. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) infection can result in the development of hepatocellular carcinoma (HCC). However, whether patients with high hepatitis B viral loads but normal levels of alanine aminotransferase (ALT) should receive antiviral treatment has been controversial. In a multinational study, the authors developed and externally validated a prognostic model of HCC risk in noncirrhotic adult patients with CHB and no notable ALT elevation. Visual Abstract. Viral Load–Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B: Chronic hepatitis B (CHB) infection can result in the development of hepatocellular carcinoma (HCC). However, whether patients with high hepatitis B viral loads but normal levels of alanine aminotransferase (ALT) should receive antiviral treatment has been controversial. In a multinational study, the authors developed and externally validated a prognostic model of HCC risk in noncirrhotic adult patients with CHB and no notable ALT elevation. Background: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB). Objective: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation. Design: Multinational cohort study. Setting: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts). Participants: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong. Measurements: Incidence of HCC. Results: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log 10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold. Limitation: Validation in cohorts of other races and receiving antiviral treatment was lacking. Conclusion: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment. Primary Funding Source: Korean government. [ABSTRACT FROM AUTHOR]

Purpose: Chronic hepatitis B virus (HBV) infection is the primary risk factor for the malignant progression of hepatocellular carcinoma (HCC). It has been reported that HBV X protein (HBx) possesses oncogenic properties, promoting hepatocarcinogenesis and chemoresistance. However, the detailed molecular mechanisms are not fully understood. Here, we aim to investigate the effects of miR-128-3p/SPG21 axis on HBx-induced hepatocarcinogenesis and chemoresistance. Methods: The expression of SPG21 in HCC was determined using bioinformatics analysis, quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC). The roles of SPG21 in HCC were elucidated through a series of in vitro and in vivo experiments, including real-time cellular analysis (RTCA), matrigel invasion assay, and xenograft mouse model. Pharmacologic treatment and flow cytometry were performed to demonstrate the potential mechanism of SPG21 in HCC. Results: SPG21 expression was elevated in HCC tissues compared to adjacent non-tumor tissues (NTs). Moreover, higher SPG21 expression correlated with poor overall survival. Functional assays revealed that SPG21 fostered HCC tumorigenesis and invasion. MiR-128-3p, which targeted SPG21, was downregulated in HCC tissues. Subsequent analyses showed that HBx amplified TRPM7-mediated calcium influx via miR-128-3p/SPG21, thereby activating the c-Jun N-terminal kinase (JNK) pathway. Furthermore, HBx inhibited doxorubicin-induced apoptosis by engaging the JNK pathway through miR-128-3p/SPG21. Conclusion: The study suggested that SPG21, targeted by miR-128-3p, might be involved in enhancing HBx-induced carcinogenesis and doxorubicin resistance in HCC via the TRPM7/Ca2+/JNK signaling pathway. This insight suggested that SPG21 could be recognized as a potential oncogene, offering a novel perspective on its role as a prognostic factor and a therapeutic target in the context of HCC. [ABSTRACT FROM AUTHOR]

Background and Aims: Molecular processes driving immune‐active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg. Methods: This study recruited 111 untreated immune‐active CHB (60 HBeAg‐positive and 51 HBeAg‐negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre‐genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core‐related antigen). Correlations between HBV markers and clinico‐virological factors influencing expression levels of HBV markers were analysed. Results: Levels of all serum markers and intrahepatic cccDNA/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg‐negative patients compared to those in HBeAg‐positive patients. Additionally, correlations between intrahepatic cccDNA/pgRNA and serum markers were impaired in HBeAg‐negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg‐positive patients, but not in HBeAg‐negative patients. Notably, among HBeAg‐positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg‐negative patients. Conclusions: HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg‐negative patients. Our findings reveal distinct disease phenotypes between immune‐active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision‐making for antiviral therapy for immune‐active CHB. [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)‐infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. Methods: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan–Meier method and Cox proportional hazard regression models to assess risk factors. Results: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06–4.41; p =.034), anthracycline (HR: 1.73, 95% CI 1.10–2.73; p =.018), baseline HBV DNA (HR: 1.55, 95% CI 1.33–1.81; p <.001) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94–31.51; p =.004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45–16.64; p =.011), baseline HBV DNA (HR: 1.48, 95% CI 1.10–1.99; p =.009) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI.95–38.87; p =.056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33–8.32; p =.010) and clinical relapse (HR: 3.59, 95% CI 1.47–8.80; p =.005) significantly correlated with all‐cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. Conclusions: The risk of virological and clinical relapse was linked to baseline HBV DNA, end‐of‐treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all‐cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high‐risk patients. [ABSTRACT FROM AUTHOR]