Medication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high-risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8-item Morisky Medication Adherence Scale (MMAS-8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS-8 scores. Of the participants, 78% were undergoing antiviral therapy, with over two-thirds (69%) reporting medium to high adherence levels. The multivariable logistic regression analysis revealed that age, knowledge of sequalae of CHB, perceived HBV stigma and possession of pharmacy plan were associated with medication adherence. Older participants had higher medication adherence than younger. High knowledge of sequalae of CHB and low perceived HBV stigma were associated with higher medication adherence. Having pharmacy plans was also associated with higher medication adherence to antiviral therapy. These findings highlight the critical role of person-related factors (e.g., knowledge and stigma) and healthcare factors in medication adherence. Future research should focus on developing targeted educational interventions focusing on personal factors to improve medication adherence among Korean American patients with CHB.

Background Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. Methods This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (>= 18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft- Gault formula (eGFR(CG)) 15-59 mL/min] or end-stage renal disease [eGFR(CG) <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. Findings 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (978%, 95% CI 924 to 997) of 93 individuals in part A (76 [974%, 910 to 997] of 78 in cohort 1 and 15 [1000%, 782 to 1000] of 15 in cohort 2) and 31 (1000%, 888 to 1000) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 10 mL/min (IQR -28 to 45) in cohort 1 and -24 mL/min (-114 to 107) in part B. Mean changes in spine and hip bone mineral density were 102% (SD 444) and 020% (325) in part A and -025% (391) and 028% (325) in part B. Interpretation Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. Funding Gilead Sciences. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Background & Aims: The investigational first -generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open -label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for > -52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary ef ficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at 24 weeks off treatment. Results: Ninety-two patients entered the extension study and received VBR + NrtI. Long-term VBR + NrtI treatment led to continued suppression of HBV nucleic acids and, to a lesser extent, HBV antigens. Forty-three patients met criteria to discontinue VBR + NrtI, with no patients achieving the primary endpoint; the majority of virologic rebound occurred > -4 weeks off treatment. Treatment was generally well tolerated, with few discontinuations due to adverse events (AEs). There were no deaths. Most AEs and laboratory abnormalities were related to elevations in alanine aminotransferase and occurred during the off -treatment or NrtI-restart phases. No drug -drug interactions between VBR + NrtI and no cases of treatment -emergent resistance among patients who adhered to treatment were observed. Conclusions: Long-term VBR + NrtI was safe and resulted in continued reductions in HBV nucleic acids following completion of the 24 -week parent studies. Following treatment discontinuation, virologic relapse was observed in all patients. This firstgeneration core inhibitor administered with NrtI for at least 52 weeks was not suf ficient for HBV cure. Clinical trial number: NCT03780543. Impact and implications: Approved treatments for chronic hepatitis B virus infection (cHBV) suppress viral replication, but viral rebound is almost always observed after treatment discontinuation, highlighting an unmet need for improved therapies possible components of finite treatment regimens for patients with cHBV. It is possible that next-generation core inhibitors with enhanced potency may produce deeper and more durable antiviral activity than first-generation agents, including vebicorvir. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction:The COVID-19 pandemic heavily impacted Asian Americans in the United States, especially those also managing underlying health conditions. Methods:A sequential, convergent mixed methods approach was used to explore pandemic-related experiences among a cohort of Korean Americans living with chronic hepatitis B (CHB). During August 2021-January 2023, structured surveys were conducted in Korean and English with 365 Korean American adult patients at clinical sites in Los Angeles, California and Philadelphia, Pennsylvania. Surveys measured physical and mental health, sociodemographic and psychosocial characteristics, and pandemic-related hardships using a newly developed index that included seven types of hardship measures. In late 2023, a purposive sample of 30 of these patients also participated in an in-depth qualitative interview that captured personal perspectives on their COVID-19 experiences. Results:Participants experienced a moderate level of COVID-19-related stressors (mean index score of 8.47 out of a possible 21) with high rates of reduced day-to-day enjoyment, fears related to their health, anti-Asian hostility, and limited access to medical care. Concerns about access to medications, financial concerns, and separation from family and friends were less common. In multivariable models, older age, stronger Korean identity, and larger body mass index were associated with lower levels of COVID-19-related stressors. Greater financial hardships and higher levels of depressive symptoms, acculturative stress, and CHB-related stigma were associated with high disease burden. Qualitative interviews taken as the pandemic waned included reflections on a wide range of negative as well as beneficial experiences. Conclusion:Clinicians caring for Asian Americans living with serious chronic diseases such as CHB would do well to consider monitoring and addressing residual psychosocial consequences of the pandemic among their most vulnerable patients.

Background. HBV-related Stigma has a detrimental impact on health outcomes of people living with HBV. Studies show that consequences of stigma include admission to school or loss of employment, impediment to marriage/having children, and barriers to accessing health services. Few studies focused on factors associated with Stigma. We examined social determinants, racial discrimination, knowledge of HBV transmission, and HBV-associated stigma among Korean American chronic hepatitis B (CHB) patients 18 years and older. Methods. As a part of ongoing project in the period of August 2021– April 2022, 291 CHB patients completed the entry survey either in Korean (n=238) or English (n=53) at two clinics in East Coast and California. The 6-question of hepatitis B quality of life (HBQOL) – stigma (n=6, alpha = .93) was administered. The construct of stigma was categorized as low/medium and high. Participants’ age, gender, marital status, employment, education, having family history of HBV infection, knowledge of HBV transmission, and racial discrimination were included. A descriptive and multivariable logistic regression analysis were used. Results. The average age of patients was 59.70 years (SD 10.34; range 24-84 years). 54% were males. The mean years of CHB diagnosis was 26.92 (SD 10.19; range 5 -52 years). The measure of racial discrimination (n=9, alpha = .87) was categorized into low, medium, and high. Multivariable logistic regression showed that gender and racial discrimination were associated with HBV-related stigma: Females had higher level of stigma than males (aOR=2.46, 95% CI: 1.42-4.27). Those with high level of racial discrimination were more likely to have stigma than those with low racial discrimination (aOR=2.27, 95% CI: 1.14-4.51). In addition, age was not linearly related to HBV stigma (see graph): Those younger than 45 years old reported the increased stigma, while those between 46 and 65 had the decreased stigma. Conclusion. This study indicates that racial discrimination and gender are important predictors of stigma in this CHB patient cohort. Future studies will identify other psychosocial factors to develop effective intervention programs to reduce stigma in consideration of younger age group. Citation Format: Hee-Soon Juon, Hie-Won Hann, SoHye Park, Ho Bae, Mimi Chang, Ann Klassen. Social determinants, racial discrimination, knowledge of HBV, and HBV-related stigma among patients with chronic hepatitis B [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B068.

Background: Hepatocellular carcinoma (HCC) is a leading cause of mortality, with Hepatitis B virus (HBV) infection as a dominant etiology worldwide. Effective early detection strategies may facilitate curative therapies and improve survival. We investigated genomic aberrations in circulating tumor DNA (ctDNA) as potential diagnostic markers of HCC in HBV-infected patients.Methods: We identified early stage (BCLC 0-A) HCC cases (n = 21) and patients without HCC (n = 14) from a cohort of Asian patients with HBV, undergoing surveillance between 2013 and 2017. Circulating cell-free DNA was isolated from blood samples, and assayed by next-generation sequencing of 23 genes implicated in HCC pathogenesis. Somatic mutations were identified using a computational pipeline. Using area under the curve (AUC) in receiver operating characteristic (ROC) analysis, we evaluated gene alterations and clinical factors in an exploratory early HCC detection model.Results: Mutant ARID1A, CTNNB1, TP53 genes were increased in HCC cases vs. non-HCC patients (85.7% vs 42.9%, P = 0.011; 42.9% vs 0%, P = 0.005; 100% vs 71.4%, P = 0.019, respectively). Using these three genes, AUC for discriminating HCC from non-HCC patients was 0.844 (95% confidence interval [CI]: 0.7317-0.9553). When combining these genes with clinical factors in an exploratory early HCC detection model, AUC increased from 0.7415 (using clinical factors alone) to 0.9354 (P = 0.041).Conclusion: Genomic aberrations in ctDNA were more prevalent in HBV-infected HCC patients compared with patients without HCC. Combining these alterations with clinical factors may identify HCC in HBV-infected patients at an early stage. These findings warrant validation in future studies. & COPY; 2023 Published by Elsevier Masson SAS.

Background & Aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core in-hibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naive patients with cHBV. Methods: HBeAg-positive, treatment-naive patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean log10 HBV DNA from Baseline to Week 12 and 24. Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log10 IU/ml HBV DNA -4.45 [1.03]) vs. PBO+ETV (-3.30 [1.18]; p = 0.0077). At Week 24, VBR+ETV led to a greater reduction from Baseline in log10 IU/ml HBV DNA (-5.33 [1.59]) vs. PBO +ETV (-4.20 [0.98]; p = 0.0084). Greater mean reductions in pregenomic RNA were observed at Week 12 and 24 in patients receiving VBR+ETV vs. PBO+ETV (p < 0.0001 and p < 0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. The safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious adverse events, or evidence of drug-induced liver injury. Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naive patients with cHBV, with a favourable safety and tolerability profile. Clinical trial number: NCT03577171 Lay summary: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naive patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Abstract Real‐world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real‐world outcomes with other first‐line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen–negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m2 was observed in the TDF‐treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV‐DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24‐month time point.

Mean (SEM) HBV DNA levels change from baseline through the end of the treatment period by Cohort Conclusion: All dose levels of ALG-000184 were well tolerated, exhibited predictable PK, and resulted in similar, substantial antiviral activity in untreated CHB subjects, regardless of HBeAg status.

BACKGROUND & AIMS:HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs. METHODS:Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks. RESULTS:Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported. CONCLUSIONS:In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone. CLINICAL TRIALS NUMBER:NCT03576066. LAY SUMMARY:Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.

(HBV DNA <LLOQ x 6 months, <20 IU/mL at screening) with moderate or severe RI or with ESRD on HD at screening while receiving TDF and/or other OAVs for 48 weeks were enrolled and switched to TAF for 96 weeks. Safety assessments including adverse events (AEs), changes in bone BMD and renal (eGFRCG, serum phosphorus serum creatinine except in ESRD patients) parameters, viral suppression, serological and biochemical responses were serially assessed. Results Of 93 patients (mod-severe RI 78; ESRD on HD 15), most (74%) were male and Asian (77%), 51% 65 y, 83% HBeAg-negative, 34% cirrhosis, and median ALT 17 U/L. Up to 24% had osteoporosis at hip and/or spine, with most having comorbidities. Twelve (13%; 11 mod-severe RI and 1 ESRD) patients discontinued the study early (5-withdrew consent, 3-deaths [none treatment-related], 2-AE, 2investigator decision). Viral suppression (HBV DNA<20IU/ mL) was maintained in all patients remaining on treatment (i.e. missing equals excluded); a high proportion had target not detected. Overall, TAF was well tolerated with no Grade 3 ,4 or serious AEs related to study treatment. Relative to baseline levels, switching to TAF resulted in small median% increases in hip/spine BMD in those with moderate to severe RI, and small median decreases in ESRD patients. 2 patients with mod-severe RI had a bone fracture (ankle, rib). Median eGFRCG increased while urinary markers of proximal tubular function progressively decreased in mod-severe RI patients. Conclusions Renally-impaired CHB patients, including ESRD patients on HD, who were switched to TAF from TDF and/or other OAVs maintained high rates of viral suppression, and bone and renal parameters remained stable or slightly improved after 2 years of treatment.

Background Study 4018, an international Phase 3 study, previously demonstrated switching to tenofovir alafenamide (TAF) vs continued tenofovir disoproxil fumarate (TDF) in suppressed chronic hepatitis B (CHB) patients has non-inferior efficacy (TAF vs TDF) with superior bone/renal safety. We analysed the efficacy and safety of switching in Asian Ethnicity (AE) patients in Study 4018. Methods CHB patients on TDF for ≥48 weeks with HBV DNA less than LLOQ for ≥20 IU/ml at screening were randomized to TAF 25mg QD or TDF 300mg QD, each with a matching placebo, and treated for 48 weeks in a double-blind (DB) fashion followed by all patients receiving open-label (OL) TAF 25 mg QD for an additional 48 weeks. Results 400/488 (82%) were AE patients who received at least 1 dose of study drug, with 195 in the TAF-TAF arm ad 205 in the TDF-TAF arm. Virologic suppression was similarly maintained at 96-wk in both groups (95%: TAF and 94% TDF). Higher percent changes in BMD from baseline (both hip and spine) were seen among the TAF-TAF group [1.2 (3.0 SD) for hip and 2.5 (4.0) SD for spine] vs TDF-TAF group [0.12 (2.8 SD) for hip and 1.5 (3.8) SD for spine]. eGFRCG increased over years in the TAF-TAF group and from Week 48 to 96 in the TDF-TAF group. There were no study drug-related treatment-emergent grade 3 or 4 AEs or SAEs. Conclusions Following TDF to TAF switch, viral suppression was maintained, with improved bone and renal safety parameters through 96 weeks in AE patients.