Hepatitis B Research Articles

HBV Transmission Knowledge Among Korean-American Chronic Hepatitis B Patients in the United States.

Chronic hepatitis B (CHB) is a condition that disproportionately affects Asian Americans in the United States. Knowledge of transmission is crucial for CHB patients to practice prevention methods to limit the spread of the hepatitis B virus (HBV), but also live their lives free from unwarranted fears or restrictions. Among Asian CHB patients, several misperceptions about HBV transmission have been identified. This analysis aims to assess the current state of HBV knowledge among a cohort of Korean-American CHB patients. This mixed-methods study includes 363 respondents who completed a survey in either Korean (N = 298) or English (N = 65) at two clinical care settings in Philadelphia (N = 161) and Los Angeles (N = 202); 30 participants also completed in-depth interviews. Knowledge was measured on a 10-point scale, asking patients yes or no transmission questions (n = 10, alpha = 0.87). The average knowledge score was 6.3. In multivariate analyses, older age was associated with lower knowledge (β=-0.25, p < 0.001). More years of formal education (β = 0.09, p = 0.076) and utilizing more sources for health information (β = 0.12, p = 0.023) were both independently associated with higher knowledge scores. Qualitative findings show that misperceptions about transmission through shared food still exist and that provider communication is an important part of knowledge acquisition. These results suggest that despite receiving specialized, culturally concordant medical care for their disease, some Korean-American CHB patients have an inadequate understanding of transmission and that opportunities exist to improve education in this population. Identifying additional factors that influence knowledge acquisition and retention is key to developing culturally effective education interventions for this population.

The efficacy and safety of addition of pegylated interferon to long-term nucleos(t)ide analogue therapy on functional cure of chronic hepatitis B patient: a systematic review and meta-analysis

ObjectiveThis 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).MethodsThis 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.ResultsSeven 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.ConclusionFor 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.

CHRONIC HEPATITIS B VIRUS INFECTION: SYSTEMATIC REVIEW OF EPIDEMIOLOGY, MECHANISMS OF VIRAL PERSISTENCE AND TREATMENT OF THE CONDITION

Objective: The general objective of this study is to analyze the scientific production on chronic infection by the Hepatitis B virus, seeking to identify the main methods used in the treatment of this pathology. Methodology: This is a systematic review focused on understanding the main aspects that permeate chronic infection by the Hepatitis B virus. The research was guided by the question: “What are the main aspects that permeate chronic infection by the Hepatitis B virus, as well as what are the diagnostic and therapeutic resources used in clinical practice?”. To find answers, searches were performed in the PubMed database using five descriptors combined with the Boolean term “AND”. This resulted in 408 articles. Twenty-four articles were selected for analysis and 15 articles were used to compose the collection. Results: The eradication of hepatitis B depends on the combination of preventive and therapeutic efforts. The persistence of cccDNA in the liver, even after viral suppression, makes complete functional cure difficult. Antivirals such as entecavir and tenofovir are effective in reducing viral load, but they fail to eradicate the virus in most patients, requiring prolonged treatments. Furthermore, the variability in treatment responses, influenced by factors such as viral genotype and disease stage, highlights the need for personalized approaches to improve clinical management. In summary, despite advances, there are still important challenges to be addressed in the search for a cure for chronic hepatitis B. Conclusion: The systematic review highlighted the main aspects of chronic hepatitis B (CHB), emphasizing its challenges and advances in clinical management. Chronic hepatitis B virus (HBV) infection remains a serious public health problem, with complications such as liver cirrhosis and hepatocellular carcinoma. Prevention strategies, such as universal vaccination and immunoprophylaxis, are effective in reducing vertical transmission, especially in newborns, but global adherence still needs to improve, especially in areas of high prevalence.

The expression of sICAM-1 influenced by Clonorchis sinensis co-infection in CHB patients.

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) has emerged as an inflammatory biomarker of many essential functions. We investigated the level of sICAM-1 influenced by Clonorchis sinensis (C. sinensis) co-infection in chronic hepatitis B (CHB) patients to explore the degree of liver tissue inflammation and liver function damage after co-infection. The study included data from patients with C. sinensis mono-infection (n=27), hepatitis B virus (HBV) mono-infection (n=32), C. sinensis and HBV co-infection (n=24), post-hepatitis B liver cirrhosis (n=18), post-hepatitis B liver cirrhosis co-infected with C. sinensis (n=16), and healthy controls (n=39). The level of sICAM-1 was measured with specific enzyme-linked immunosorbent assay method. Compared to the healthy control group, all the experimental groups had significantly higher serum sICAM-1 levels. The levels of sICAM-1 in co-infected groups were significantly higher compared to the mono-infection groups and were positively correlated with the levels of glutamate aminotransferase (ALT) and aspartate aminotransferase (AST). Our research findings confirmed that co-infection could exacerbate liver tissue inflammation and liver function damage in patients, could raise the sICAM-1 level, and may lead to the chronicity of HBV infection. These results provide clues for pathological mechanism study and formulating treatment plans.

Asiatic acid inhibits HBV cccDNA transcription by promoting HBx degradation

BackgroundHepatitis 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.MethodsThe 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.ResultsAsiatic 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.ConclusionsAsiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.

Diagnostic accuracy of FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis in patients with chronic hepatitis B with metabolic dysfunction-associated fatty liver disease

Objective To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC). Results A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+F ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+F ≥ 2 was 0.739 (p < 0.001), 0.643 (p = 0.006), 0.754 (p < 0.001), and 0.665 (p = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (p = 0.038), 0.725 (p = 0.001), 0.851 (p < 0.001), and 0.560 (p = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively (p < 0.05). Conclusion In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.

Factors associated with low hepatitis B surface antigen levels in chronic hepatitis B patients treated with nucleot(s)ide analogs.

Several studies have reported that chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels (100 or 10IU/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 1year. The cumulative incidence rates of achieving low HBsAg levels at 5 and 10years post-NA administration were as follows: 19.0% and 29.2% for HBsAg <100IU/mL, 13.8% and 17.6% for HBsAg <10IU/mL, and 9.5% and 13.5% for HBsAg <0.05IU/mL, respectively. Hepatitis B virus genotypes other than genotype C (hazard ratio [HR] 3.47; p<0.001) and an HBsAg level <1000IU/mL at the start of NA therapy (HR 2.49; p=0.008) were significantly associated with achieving HBsAg levels <100IU/mL. Among 27 patients who discontinued NA therapy, 5 patients with HBsAg levels <100IU/mL and HBcrAg levels <3logU/mL at the time of discontinuation did not experience virological relapse. The cumulative rates of achieving HBsAg levels <100IU/mL were relatively high. Discontinuation of NA may be considered based on HBsAg and HBcrAg levels during the course of NA therapy.

Comparative Evaluation of Fibrosis Markers in Obese and Non-Obese Patients with Chronic Hepatitis B: A Focus on FIB-4 and APRI

Aim: Chronic Hepatitis B (CHB) is a global health issue with significant morbidity and mortality. This study aims to evaluate the impact of obesity on fibrosis progression in CHB patients by comparing non-invasive fibrosis markers between obese and non-obese patients. Material and methods: A total of 172 CHB (50.6±9.4 mean aged) patients were included in this retrospective study. Height, body weight, and waist circumferences of the patients were measured, and liver function tests and biochemical parameters were studied. Fibrosis-4 score (FIB-4) and Aspartate Aminotransferase-Platelet Ratio Index (APRI) were calculated. Results: No significant differences were found between the groups regarding age (p=0.500) or gender distribution (p=0.277). While Alanin Aminotransferase levels did not differ significantly between the groups (p=0.498), Aspartate Aminotransferase levels were significantly higher in obese patients (p

Nucleos(t)ide analogues potentially activate T lymphocytes through inducing interferon expression in hepatic cells and patients with chronic hepatitis B

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.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

Hepatitis Delta Virus Testing and Prevalence Among Chronic Hepatitis B Patients Across Three U.S. Safety-Net Health Systems

Background & AimsDespite a high prevalence of risk factors associated with hepatitis delta virus (HDV) infection among safety-net populations, data evaluating HDV testing and prevalence are limited. We aim to evaluate HDV testing practices and HDV prevalence among an ethnically diverse, multi-center cohort of safety-net patients with chronic hepatitis B (CHB). MethodsWe retrospectively evaluated 13,218 patients with CHB (54.2% male, 57.9% non-white minorities, 12.5% HIV, 23.0% HCV) across three U.S. safety-net health systems from 2010-2022 to evaluate proportion tested for HDV and proportion positive among those tested. Adjusted multivariate logistic regression models evaluated for predictors of HDV testing and predictors of anti-HDV positive. ResultsAnti-HDV testing was performed in 6.1% overall and in 4.9% that met AASLD criteria for HDV testing. Greater odds of testing was observed in men vs. women (OR 1.49, 95%CI 1.27–1.75), Asian individuals vs. white individuals (OR 2.18, 95%CI 1.74-2.72), black/African American individuals vs. white individuals (OR 1.29, 95%CI 1.07-1.56), and patients with Medicare or Medicaid. Among CHB patients tested for HDV, 15.7% were positive (22.9% among those meeting AASLD HDV testing criteria). Only 2 (1.6%) patients had follow-up HDV RNA testing. Greater proportion of anti-HDV positive was observed in patients with baseline cirrhosis (47.4% vs. 13.3%, p<0.001), and patients with Medicare or Medicaid vs. those with commercial insurance. ConclusionsAmong an ethnically diverse, multi-center safety-net cohort of CHB patients, low rates of HDV testing were observed, even among those with high-risk HDV risk factors. Among those tested, 15.7% were positive, only 2 had follow up RNA testing. This highlights the need for greater awareness, education, and advocacy to improve HDV testing rates.

Undergraduate health science students' knowledge, attitudes, and practices about hepatitis B virus infection prevention at Addis Ababa university, Ethiopia: a cross-sectional study

Background: Hepatitis B (HB) is a serious liver-damaging infection that is caused by the HB virus (HBV). Healthcare professionals are especially susceptible to HB, a serious global public health concern. The aim of this study was to assess the undergraduate health science students’ knowledge, attitudes, and practices regarding the prevention of HBV infection. Methods: A cross-sectional study was conducted among third- and fourth-year health science students at the college of health sciences (CHS), Addis Ababa university (AAU) in Ethiopia. Self-administered structured questionnaire was used to collect the data. Chi square was used to examine the relationship between the outcome variables (mean knowledge, attitude, and practice) and a few socio-demographic factors (age, sex, and year of study). Statistical significance will be determined by p values less than 0.05. Results: Half of the study participants had adequate knowledge about the HBV. More than half (55%) of research participants were in favor of the HBV vaccination. The Chi square test was used to look at the association between the participants' mean knowledge score and specific socio-demographic characteristics. However, no significant association has been found with any of the selected socio-demographic variables. Conclusions: While undergraduate health science students generally demonstrate an acceptable level of knowledge and positive attitudes toward HBV infection prevention, there remain significant gaps in practice, particularly regarding vaccination uptake and adherence to standard precautions.

Impact of age at HBsAg seroclearance on hepatic outcomes and life expectancy in men with chronic HBV infection based on multi-state modeling of the natural history.

The effects of age at HBsAg seroclearance on clinical outcomes and survival in chronic hepatitis B (CHB) have not been adequately assessed. We evaluated the impact of age at HBsAg seroclearance on long-term outcomes, along with how coexisting factors modified risks and life expectancy in CHB patients. We used multi-state modeling approach to examine transitions through the CHB continuum in a longitudinal cohort study of male civil servants recruited in 1989-1992. Hepatic outcomes and deaths were identified by clinical evaluation and linkage with national health databases. Four sets of risk factors (CHB-related, metabolic, lifestyle, and genetic factors) were assessed. Of 2551 HBsAg carriers, with follow-up until 2021 or death, 695 achieved HBsAg seroclearance, 490 developed cirrhosis (88 decompensated), 252 developed hepatocellular carcinoma (HCC), and 652 died. The cumulative rates for HCC were 1.1% and 1.5% at 10years after HBsAg seroclearance, respectively, for patients achieving seroclearance at age 50 and 60; correspondingly, the rates for cirrhosis were 2.3% and 3.0%. Developing HBsAg seroclearance was associated with a reduced risk of cirrhosis (HR = 0.37, 95% CI 0.15-0.92) but not HCC. Patients experiencing HBsAg seroclearance lived longer years free of major liver diseases than HBsAg-persistent patients, and achieving seroclearance at age 50 (vs 60) led to a greater increase in the disease-free life expectancy. However, obesity and smoking were associated with adverse hepatic outcomes and loss of the disease-free life expectancy following HBsAg seroclearance. Our findings highlight the benefit of earlier HBsAg seroclearance for gains in disease-free life expectancy and the impact of obesity and smoking on loss of the life years free of major liver diseases following HBsAg seroclearance.

Integrated metabolomics and network pharmacology to explore the clinical efficacy and mechanism of Yinchenhao decoction combined with nucleoside analogues on chronic hepatitis B

Yinchenhao decoction (YCHD) is widely used in the treatment of damp-heat syndrome of chronic hepatitis B (CHB), but it remains unclear about the active compounds in YCHD and its potential mechanism for treating CHB. The purpose of this work is to evaluate the clinical efficacy of YCHD combined with nucleoside analogues (NAs) for the treatment of CHB. Besides, based on the exact clinical efficacy, we combined serum metabolomics and network pharmacology to screen differential metabolites and related pathways regulated by YCHD to investigate the possible mechanism for treating CHB. It revealed that NAs plus YCHD could significantly improve alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increase HBV-DNA negative rate (P<0.05), reduce the levels of inflammatory factors and LSM (both P<0.05), regulate lipids (P<0.05), and improve the symptoms of traditional Chinese medicine (TCM) (P<0.05) in CHB patients. YCHD was relatively safe. It showed 30 active compounds including chlorogenic acid, geniposide, emodin, quercetin, kaempferol, β-sitosterol and aloe emodin, and 115 key targets which were related to the regulation of lipids and reduction of oxidative stress related to the effect of YCHD in CHB in the network pharmacology analysis. We found 9 core targets and 4 key metabolites according to metabolomics, which were partly consistent with the network pharmacology findings. It proved that network pharmacology combined with metabolomics can well explain the “multi-component-multi-target” mechanism of complex TCM.

A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B

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&lt;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&lt;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&lt;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&lt;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. doi: https://doi.org/10.12669/pjms.40.10.10307 How to cite this: Wang H, Wu L. A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B. Pak J Med Sci. 2024;40(10):2390-2394. doi: https://doi.org/10.12669/pjms.40.10.10307 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment.

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.

Antiviral Therapy for Chronic Hepatitis B with Mildly Elevated Aminotransferase: A Rollover Study from the TORCH-B Trial.

Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Association between Chronic Hepatitis B/C and Incidence of Osteoporosis and Bone Fractures: Results from a Retrospective Cohort Study.

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.

Association of vitamin D with functional cure in chronic hepatitis B: Insights from a retrospective cohort study and an intervention study

Background & AimFunctional cure for chronic hepatitis B (CHB) patients can be achieved using nucleos(t)ide analogues (NAs) and pegylated interferon alpha (Peg-IFNα) combination treatment. However, the role of vitamin D in functional cure remains unclear. We aimed to investigate the association between vitamin D levels and functional cure in CHB patients. MethodsA retrospective study was conducted to detect changes in serum 25-hydroxyvitamin D (25(OH)D) levels in 526 CHB patients. Furthermore, an intervention study was conducted on 90 CHB patients with baseline vitamin D insufficiency, and 45 patients were randomly assigned to the control group receiving NAs/Peg-IFNα treatment, whereas the remaining patients were categorized into the vitamin D group (VD group) receiving NAs/Peg-IFNα treatment combined with vitamin D supplementation at 800 IU/day. ResultsA retrospective study revealed a progressive elevation in serum 25(OH)D levels throughout the duration of treatment. The cured group displayed significantly higher serum 25(OH)D levels than the uncured group (P = 0.046) at the end of treatment, and the changes in serum 25(OH)D (Δ25(OH)D) levels between the two groups were found to be significantly different (P < 0.0001). In the intervention study, the VD group tended to have an increased functional cure rate (48.0%) compared with the control group (34.3%) in the binary logistic regression equation analysis (P = 0.09). Notably, a linear mixed-effects model in the longitudinal analysis indicated a significant impact of serum 25(OH)D levels on treatment outcomes (P = 0.017). ConclusionsSerum 25(OH)D and Δ25(OH)D were both positively associated with functional cure in this retrospective study, and vitamin D supplementation may be helpful for functional cure in CHB patients. Registration number of Clinical TrialChiCTR1800020108.

Predicting clinical outcomes in chronic hepatitis B patients receiving nucleoside analogues and pegylated interferon alpha: a hematochemical and clinical analysis

BackgroundThe 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.MethodsWe 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).ResultsA 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.ConclusionThis 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.