Hepatitis B Research Articles

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.

ELISA genotyping of hepatitis B virus in China with antibodies specific for genotypes B and C

Hepatitis B virus (HBV) causes hepatitis B (HB) and distinct HBV genotypes can lead to different prognoses. However, HBV genotyping is rarely done in clinics, because the traditional method by PCR-based DNA sequencing is impractical for clinical diagnosis with tedious process and low success rate. Herein, we have established an ELISA-based genotyping method to quickly determine the HBV genotypes of HB patients in China. First, two commercial antibodies, 16D12 and 6H3 specific for HBV genotypes B and C respectively, are chosen as capture antibodies, since these two genotypes dominate in China. Then two home-made genotype-specific antibodies, B19 and C04, are used as the detection antibodies for genotypes B and C in sandwiched ELISA. The ELISA kit shows high sensitivity (> 95%) and specificity (> 95%) in detecting genotypes B and C of Chinese HB patients. Moreover, the ELISA kit has demonstrated higher success rate (98.7%) than PCR-based DNA sequencing (93.5%) and a commercial PCR-based genotyping kit (92.2%) for sera with HBV DNA ≥ 1000 IU/mL and HBsAg ≥ 250 IU/mL. Such an advantage is more obvious for the sera with HBV DNA < 1000 IU/mL. The kappa analysis between the ELISA and PCR-based DNA sequencing results exhibits a kappa of 0.836, indicating a good correlation.

Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B

Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of “piecemeal necrosis”. In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.

Real-world trends in acute viral hepatitis in Japan: A nationwide questionnaire-based survey.

The actual incidence of acute viral hepatitis in Japan remains unclear. We aimed to investigate trends in the incidence of acute hepatitisB and C infections in Japan. A nationwide, multicenter, retrospective questionnaire-based survey was conducted. Participating hospitals received questionnaires through nationwide geographically distributed regional core centers certified as specialists in hepatitis treatment. The questionnaire included hospital size and the number of patients diagnosed with acute hepatitisB or C during each fiscal year (FY) from 2015 to 2022. The sex distribution in each FY was also documented. Comparisons were made before and during the COVID-19 era (2015-2019 vs. 2020-2022), and between populous and non-populous prefectures. Responses to the questionnaires were obtained from 127 institutions in 29 prefectures covering eight regions in Japan. A median of 127.0 patients with acute hepatitisB (interquartile range [IQR] 106.5-131.8 patients) were reported during each FY, and the incidence significantly decreased during the fiscal years 2020-2022 compared with the fiscal years 2015-2020 (median 96.0 [IQR 91.0-103.0] patients vs. 131.0 [IQR 128.0-134.0] patients; p=0.03). A median of 10.0 (IQR, 7.8-13.5) patients were reported with acute hepatitisC during each FY. The proportions of men in acute hepatitis B and C were significantly higher in populous prefectures. Populous prefectures had a higher proportion of men among viral hepatitis patients than non-populous prefectures. Estimating the high-risk populations in each area could provide insights to advance the elimination of viral hepatitis.

Introduction of a hexavalent vaccine containing acellular pertussis into the national immunization program for infants in Peru: a cost-consequence analysis of vaccination coverage

BackgroundInfant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru’s infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months).MethodsThe analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses.ResultsThe overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis.ConclusionsImplementation of the hexavalent vaccine in Peru’s National Immunization Program has a positive public health cost consequence.

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.

Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level

BackgroundChronic 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.MethodsWe 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.ResultsAmong 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.ConclusionsA 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.

Effects of tenofovir disoproxil fumarate on intrahepatic viral burden and liver immune microenvironment in patients with chronic hepatitis B

BackgroundThe impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear.ObjectiveWe aimed to characterise the effects of tenofovir disoproxil...

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.

A Chronic Hepatitis B Identification and Surveillance Program Improves Care in an Integrated Health Plan.

Optimal management of patients with chronic hepatitis B (CHB) requires surveillance for hepatocellular carcinoma (HCC) and identification of antiviral therapy candidates, but few dedicated CHB surveillance models have been described. Kaiser Permanente Northern California developed a systematic CHB surveillance and management program in 2012. We report the results of the program's performance over the initial 8-year period. We conducted a retrospective cohort study of all patients with CHB meeting guideline criteria for HCC surveillance. Eligible patients were invited into the Kaiser Permanente Northern California Liver Care Program (LCP), wherein patients receive reminders to obtain semiannual laboratory and imaging surveillance, which are reviewed by nurse practitioners. Treatment-eligible patients are provided with antiviral medications. Since its inception, 14,630 patients met study criteria, and 9,373 (64.1%) enrolled in the LCP. Adherence to imaging recommendations was higher in the LCP-managed group (41.5% of patients in the LCP received ≥80% of recommended imaging compared with 10.9% among patients not enrolled [risk ratio = 3.8; P < 0.001]). Approximately 63% of treatment-eligible patients in both groups received medication, although full-adherence rates were higher in patients managed in the LCP (72.3% vs 63.4%, respectively, P < 0.001). Among the 197 patients who developed HCC, recommended surveillance imaging was performed more frequently among LCP-managed patients (71.4% vs 53.8%, respectively, P < 0.05) who were also significantly more likely to be diagnosed at Barcelona Clinic Liver Cancer Stage 0/A (95.9% vs 74.6%; P < 0.001). In this integrated healthcare system, a systematic program for surveilling and managing patients with CHB seemed beneficial for both process and clinical endpoints.

Association of hepatitis B virus and thyroid hormones during pregnancy.

This study aims to evaluate the correlation between serum thyroid hormone levels and hepatitis B virus (HBV) DNA and HBV genotypes in pregnant women with chronic hepatitis B. A total of 96 pregnant women with chronic HBV-infected pregnant women between January 2020 and December 2022 were selected as the observational study subjects. About 50 HBV-uninfected pregnant women during the same period were selected as the control group. Serum thyroid hormone levels at different stages of pregnancy, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroperoxidase antibody (TPOAb), and thyroglobulin antibody (TGAb), were compared between the 2 groups. Thyroid hormones levels were also compared between HBV-DNA-positive and HBV-DNA-negative women in the HBV-infected pregnancy group, and to determine the correlation between thyroid hormones levels and HBV-DNA load and HBV genotype in HBV-DNA-positive pregnant women. The TSH levels in mid and late pregnancy and TPOAb levels in early, mid, and late pregnancy of HBV-infected pregnant women were higher than those in the same period in HBV-uninfected pregnant women (P < .05). The TPOAb and TGAb levels in early, mid, and late pregnancy of HBV-DNA-positive pregnant women were higher than those in the same period in HBV-DNA-negative pregnant women (P < .05). The HBV-DNA load and FT3 or FT4 levels were negatively correlated (P < .05), and the HBV-DNA load and TGAb levels were positively correlated (P < .05). However, there was no statistical difference in thyroid hormone levels between different HBV genotypes (P > .05). The thyroid hormone levels will change in pregnant women infected with hepatitis B virus, and there is a certain correlation between HBV-DNA load and thyroid hormone levels. Therefore, timely monitoring of thyroid hormones and HBV-DNA load can provide early prevention and treatment for HBV infection in pregnant women, ensuring the health of pregnant women and fetuses.

The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment

BackgroundHepatitis B surface antigen (HBsAg) loss is regarded as a pivotal criterion for assessing functional cure in patients diagnosed chronic hepatitis B (CHB). We conducted the research to investigate the real-world performance of HBsAg seroconversion in sustaining HBsAg loss.MethodsThis retrospective analysis confirmed 295 patients who attained HBsAg loss through combination therapy involving nucleos(t)ide analogues (NAs) and pegylated interferon alpha (peg-IFNα). Employing Kaplan–Meier estimates method to conduct survival analysis. The forest plot was used to visualize the results of multivariate Cox regression, and selected variables were included in the nomogram.ResultsHBsAg seroreversion was observed in 45 patients during follow-up periods, with a lower recurrence risk in patients with HBsAg seroconversion at the end of peg-IFNα therapy (EOT) (10.3% vs 37.3% at 96-week, P < 0.0001). Moreover, the sustainability of hepatitis B surface antibody (anti-HBs) in participants continuing therapy after HBsAg seroconversion was superior to those discontinued prematurely (72.5% vs 54.5% at 96 weeks, P = 0.012). Additionally, the former group was also relatively less likely to experience HBsAg reversion during long-term observation (8.4% vs 14.3% at 96 weeks, P = 0.280). Hepatitis B envelope antigen (HBeAg) status, anti-HBs status and consolidation treatment screened by multivariable analysis were utilized to construct a predictive model for HBsAg reversion. The concordance index(C-index = 0.77) and calibration plots indicated satisfactory discrimination and consistency of nomogram.ConclusionsHBsAg seroconversion was beneficial for sustaining functional cure in patients treated with peg-IFNα. Continuing consolidation therapy after HBsAg seroconversion also contributed to maintain HBsAg seroconversion and improve the durability of HBsAg loss. The nomogram illustrated its efficacy as a valuable instrument in showcasing survival probability of functional cure.

Dynamic Changes of Growth and Thyroid Function in Young Children With Chronic Hepatitis B Treated With Peginterferon Monotherapy.

Peginterferon (PegIFN) has shown promising results in the treatment of chronic hepatitis B (CHB). This study aimed to evaluate the effects of PegIFN α-2b on growth and thyroid function in young children with CHB. A retrospective study was performed by extracting clinical data from children with CHB who received PegIFN α-2b monotherapy at the Public Health Clinical Center of Chengdu between June 2017 and December 2020. Mean, SD, independent samples t test and 1-way repeated analysis of variance were used to evaluate relevant data. A total of 62 children were included in this study. Overall, significant differences were observed in the weight-for-age z score (WAZ), height-for-age z score (HAZ) and body mass index-for-age z score (BAZ) at different time points ( P < 0.001). WAZ, HAZ and BAZ were not affected by PegIFN α-2b at 24 weeks of treatment (all P > 0.05). WAZ, HAZ and BAZ at the end of treatment and 48 weeks after treatment; WAZ at 96 weeks after treatment were lower than baseline levels (all P < 0.05). No statistical differences were found in HAZ and BAZ at 96 weeks after treatment compared with baseline. Thyroid dysfunction developed in 17.7% of children during the treatment. Thyroid dysfunction was transient and had no effect on growth. PegIFN α-2b has inhibitory effects on growth and can increase the incidence of thyroid dysfunction in young children with CHB. These effects are generally reversible with the cessation of therapy, although WAZ had not returned to baseline after 96 weeks of observation.

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.

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.

Effects of tenofovir alafenamide fumarate on serum lipid profiles in patients with chronic hepatitis B

BackgroundConcerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB.MethodsA total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF).ResultsIn this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334–5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836–21.328, P < 0.001).ConclusionsCompared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.

Intrahepatic Exhausted Antiviral Immunity in an Immunocompetent Mouse Model of Chronic Hepatitis B

Targeting exhausted immune systems would be a promising therapeutic strategy to achieve a functional cure for HBV infection in patients with chronic hepatitis B (CHB). However, animal models recapitulating the immunokinetics of CHB are very limited. We aimed to develop an immunocompetent mouse model of CHB for intrahepatic immune profiling. CHB mice were created by intrahepatic delivery of the Sleeping Beauty transposon vector tandemly expressing the hepatitis B virus (HBV) genome and fumarylacetoacetate hydrolase (FAH) cDNA into C57BL/6J congenic FAH knockout mice via hydrodynamic tail vein injection. We profiled the viral and intrahepatic immune kinetics in CHB mice with or without treatment with recombinant IFNα or the hepatotropic Toll-like receptor 7 agonist SA-5 using single-cell RNA-seq. CHB mice exhibited sustained HBV viremia and persistent hepatitis. They showed intrahepatic expansion of exhausted CD8+ T (Tex) cells, the frequency of which was positively associated with viral load. Recruited macrophages increased in number but impaired inflammatory responses in the liver. The cytotoxicity of mature natural killer (NK) cells also increased in CHB mice. IFNα and SA-5 treatment both resulted in viral suppression with mild hepatic flares in CHB mice. Although both treatments activated NK cells, SA-5 had the capacity to revitalize the impaired function of Tex cells and liver-recruited macrophages. Our novel CHB mouse model recapitulated the intrahepatic exhausted antiviral immunity in patients with CHB, which might be able to be reinvigorated by a hepatotropic TLR7 agonist.

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.

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.