Chronic Hepatitis B Patients Research Articles

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.

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.

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.

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.

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 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.

Monocyte-derived Galectin-9 and PD-L1 differentially impair adaptive and innate immune response in chronic HBV infection and their expression remain unaltered after antiviral therapy.

Patients with chronic HBV infection (CHI) exhibit defective anti-viral 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. Immune-checkpoint 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 T-cells, 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. Collection of blood and liver-tissue samples from HBV infected patients and controls, flow-cytometry, cell sorting, cell culture and immune-fluorescence were performed for this study. Gal-9+ and PD-L1+-monocytes were significantly increased in HBeAg-positive 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 HBV-specific-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. 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.

Multiple Low-Level Viraemia Suggest Hindered Liver Fibrosis Regression in Chronic Hepatitis B Patients During Antiviral Therapy.

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.

Hepatitis Delta Virus Testing, Prevalence, and Liver-Related Outcomes Among U.S. Veterans with Chronic Hepatitis B

Background and AimsHepatitis delta virus (HDV) infection in patients with chronic hepatitis B (CHB) is associated with worse liver-related outcomes. We aim to comprehensively evaluate HDV testing, diagnosis, and liver-related outcomes among a national cohort of U.S. Veterans with CHB. MethodsU.S. Veterans with CHB from 2010 to 2023 were evaluated to determine trends in HDV testing (anti-HDV antibody, HDV RNA) and proportion positive among those tested. HDV positive patients were 1:2 propensity score matched to CHB patients who were HDV negative to evaluate incidence (per 100,000 person-years) of cirrhosis, hepatic decompensation, or hepatocellular carcinoma using competing risks Nelson-Aalen methods for estimating cumulative hazards. ResultsAmong 27,548 CHB patients identified, 16.1% completed HDV testing, among whom 3.25% (n=144) were positive. After excluding patients with cirrhosis or HCC at baseline, 71 patients with HDV (median follow-up 5.3 years, IQR 2.5-7.6) were propensity score matched to 140 CHB patients without HDV (median follow-up 4.5 years, IQR 2.6-8.1). Compared to CHB patients without HDV, those with concurrent HDV had significantly greater incidence of cirrhosis (4.39 vs. 1.30 per 100,000 person-years, p < 0.01) and hepatic decompensation (2.18 vs. 0.41 per 100,000 person-years, p=0.01). ConclusionAmong a national cohort of U.S. Veterans with CHB, low rates of HDV testing were observed. This is concerning given that patients with concurrent HDV infection had >3 times and >5 times greater risks of cirrhosis and hepatic decompensation, respectively, compared to CHB patients without HDV, highlighting the importance of timely HDV diagnosis and treatment.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos/tide analogue therapy

Background & AimsThe dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos/tide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes. MethodsUtilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase (ALT), and with liver fibrosis/cirrhosis. ResultsWe retrieved data from 1885 adults on NA treatment (median follow-up 6.2 years, interquartile range (IQR) 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n=1367, discrimination: 0.93, entropy: 0.90): class 1 ‘long term suppression’ (n=827, 60.5%), class 2 ‘timely virological suppression’ (n=254, 18.6%), class 3 ‘persistent moderate viraemia’ (n=140, 10.2%), class 4 ‘persistent high-level viraemia’ (n=44, 3.2%), and class 5 ‘slow virological suppression’ (n=102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n=518). ALT decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p<0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had 2-fold increased hazards of fibrosis/cirrhosis compared to class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02). ConclusionsHeterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression.

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis.

Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis. Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66-0.86) and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Efficacy of short-term Peg-IFN α-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: a retrospective cohort study

PurposePeginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy.MethodsIn this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance .ResultsBy week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance.ConclusionOur findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance.

Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials.

In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Here, we report the studies' final 8-year results. CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Among 1298 patients randomised to double-blind TAF (n = 866) or double-blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing-equals-failure analysis) and 95%, 94% and 97% (missing-equals-excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft-Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double-blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. gov numbers NCT01940341 and NCT01940471.

Sociodemographic Disparities in Hepatitis B Treatment: A Real-World Analysis of 3 Safety-Net Health Systems in the United States

Abstract 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 &amp;lt; .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.

Associated Factors for Liver Fibrosis and Histological Activity Index in Treatment-Naïve HBeAg-Positive Chronic Hepatitis B Infection: Insights from a Retrospective Analysis.

The study aimed to identify predictors of advanced fibrosis score and histological activity index (HAI) in HBeAg-positive patients to facilitate early disease detection and reduce the need for invasive biopsies. The single-center retrospective study included treatment-naïve HBeAg-positive chronic hepatitis B (CHB) patients. Patients with HAI ≥6 and/or fibrosis ≥2 were considered to have significant liver damage. Independent determinants were identified by univariate and multivariate logistic regression analysis. Cut-off values for variables were determined by receiver operating characteristics (ROCs) curve analysis. The study enrolled a cohort of 66 patients, with 51.5% male and a median age of 26 (22.7-34.2) years. In assessing necroinflammation, no significant differences were observed in age and gender between patients with HAI <6 and HAI ≥6. However, patients with HAI ≥6 exhibited higher aspartate aminotransferase (AST) levels compared to those with HAI <6. Furthermore, lower albumin levels and platelet (PLT) counts, along with higher fibrosis-4 (FIB-4) scores, were associated with HAI ≥6. In the evaluation of fibrosis, while gender distribution did not differ significantly, patients with fibrosis grade ≥2 were older and had higher HAI scores, HAI ≥6 ratios, and FIB-4 scores compared to those with fibrosis grade <2. Multivariate analysis identified albumin as a significant predictor for both HAI ≥6 and fibrosis grade ≥2. The area under ROC (AUROC) values of albumin for predicting HAI ≥6 and fibrosis ≥2 were 0.696 and 0.698, respectively, indicating moderate predictive ability. Albumin was found to be an independent predictor of liver damage in HBeAg-positive CHB patients. The fact that the optimal threshold values detected for both HAI ≥6 and fibrosis ≥2 in this patient group were close to normal values suggests that clinicians should be more cautious in monitoring albumin levels and other pre-defined parameters to avoid delays in diagnosis.

Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B

ABSTRACT Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.