Background/Aims Achieving functional cure (hepatitis B surface antigen [HBsAg] loss) and discontinuing lifelong nucleos(t)ide analog (NUCs) therapy are critical clinical goals in chronic hepatitis B (CHB) management. This study evaluated the long-term clinical outcomes and cost-effectiveness of different treatment strategies aimed at functional cure in hepatitis B e antigen (HBeAg)-negative patients with CHB across Asia-Pacific income strata. Methods A Markov state-transition model was developed to project 30-yr hepatitis B virus (HBV) disease outcomes in HBeAg-negative patients. Three finite strategies, PegIFN add-on to NUCs (PegIFN+NUC), switching from NUCs to PegIFN (Switch), and bepirovirsen add-on to NUCs (Bepi+NUC), were compared with lifelong NUC therapy. Analyses were stratified by country income level (high-income country [HIC], upper-middle-income country [UMIC], and lower-middle-income country [LMIC]). Costs were estimated from the health care payer perspective in 2023 USD. Incremental cost-effectiveness ratios (ICERs), probabilistic sensitivity analyses, and cost-effectiveness acceptability curves were generated across a range of willingness-to-pay thresholds. Results Switch led to the largest reduction in hepatocellular carcinoma (31%) and HBV-related deaths (32%). In HIC, Switch was the dominant strategy (lower cost and higher quality-adjusted life years [QALYs] than standard care). In UMIC and LMIC settings, Switch remained highly cost-effective with ICERs of 1774 and 2200 per QALY gained, respectively. Probabilistic sensitivity analysis demonstrated a >89% probability of finite PegIFN strategies being cost-effective at 1× GDP per capita thresholds across all income strata. In contrast, the bepirovirsen add-on strategy was dominated in all settings due to high acquisition costs and the impact of modeled seroreversion on long-term gains. Conclusions Finite PegIFN-based combination therapies are cost-effective toward functional cure in AP region. While bepirovirsen represents a major milestone in HBV drug development, its current economic viability is limited by high costs and durability concerns. Policy efforts should prioritize optimizing established immunomodulatory combinations to accelerate global hepatitis B elimination.
Background/Aims Sarcopenia is associated with adverse outcomes in patients with end-stage liver disease (ESLD), but the relative contribution of muscle quantity versus muscle quality to posttransplant outcomes remains incompletely understood. Radiological indices such as psoas muscle area index (PMAI), transverse psoas muscle thickness index (TPMTI), and psoas muscle density index (PMDI) provide objective measures of muscle mass and myosteatosis. This study aimed to explore phenotypic patterns in ESLD patients using clinical and radiological parameters and examine their association with 1-yr posttransplant mortality. Methods In this retrospective study, 86 adult ESLD patients who underwent liver transplantation were analyzed. Clinical and radiological variables (age, PMAI, TPMTI, PMDI, MELD, Child–Turcotte–Pugh score, and body mass index) were normalized and subjected to hierarchical and k-means clustering to identify phenotypic groups. One-year posttransplant mortality rates were compared across clusters. Receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of PMDI. Results Five phenotypic clusters were identified, demonstrating heterogeneity in muscle quantity, muscle quality, and disease severity. A cluster characterized by relatively preserved muscle mass but reduced muscle density exhibited the highest 1-yr mortality (41.7%), whereas a cluster with preserved muscle density showed no mortality although these data were limited by a small sample size. Intermediate clusters demonstrated mortality rates ranging from 15.8% to 17.9%. PMDI showed modest discriminative ability for 1-yr mortality (area under the curve [AUC] 0.662), comparable to MELD (AUC 0.659). Conclusion Exploratory clustering analysis suggests that phenotypic variation in muscle composition exists among ESLD patients undergoing liver transplantation, with differential associations with short-term mortality. Muscle quality, as reflected by PMDI, may provide additional prognostic information beyond conventional measures of disease severity. These findings are hypothesis generating and require validation in larger, prospective studies before clinical application.
Background/Aims Chronic liver disease (CLD) is associated with major metabolic disturbances. Although an elevated atherogenic index of plasma (AIP) reflects cardiometabolic risk, progressive liver dysfunction may instead be accompanied by lipid depletion, suggesting a “lipid paradox.” We aimed to investigate its intrahepatic transcriptomic basis, systemic manifestations, and clinical implications using an integrative molecular-to-population approach. Methods Intrahepatic transcriptomic data from the Gene Expression Omnibus were analyzed to identify differentially expressed genes associated with chronic hepatitis B progression, and hub genes were screened by machine learning. National Health and Nutrition Examination Survey (NHANES) 2015–2018 data were used to examine the association between the Fibrosis-4 (FIB-4) and AIP using survey-weighted models and mediation analyses. Data from the China Health and Retirement Longitudinal Study (CHARLS) were used to model 4-yr AIP trajectories and explore associations with cardiometabolic outcomes and all-cause mortality. Results Transcriptomics identified nine immune-fibrotic hub genes; functional enrichment showed immune activation and matrix remodeling with suppressed lipid metabolism. In NHANES, higher fibrosis risk was independently associated with lower AIP, with mediation more consistent with metabolic depletion than inflammation and independent of the age term in FIB-4. In CHARLS, individuals with liver disease showed an attenuated AIP trajectory; within this subgroup, lower AIP was associated with a higher prevalence of cardiovascular disease and metabolic syndrome, with an exploratory adverse survival signal. Conclusion Across transcriptomic, cross-sectional, and longitudinal analyses, reduced AIP in CLD may reflect metabolic and nutritional vulnerability rather than cardiometabolic protection, warranting further evaluation as an indicator for risk stratification.
Background/Aims Gastric antral vascular ectasia (GAVE) is a significant cause of recurrent upper gastrointestinal (GI) bleeding in patients with liver cirrhosis. Conventional endoscopic therapies, including argon plasma coagulation (APC) offer temporary relief but high recurrence rates necessitates the need for effective adjunctive pharmacotherapy. Thalidomide, with its anti-angiogenic and immunomodulatory properties, has emerged as a promising therapeutic agent. This study aimed to evaluate the effectiveness and safety of thalidomide therapy in reducing hospitalisation, blood transfusion requirements, and need for APC sessions in cirrhotic patients with GAVE-related recurrent upper GI bleeding. Methods In this single-centre prospective observational pilot study, we enrolled 32 consecutive patients with confirmed liver cirrhosis and endoscopically diagnosed GAVE presenting with recurrent upper GI bleeding between 2022 and 2024. As a pilot study focused on a rare condition, no formal sample size calculation was performed; consecutive eligible patients were enrolled over the study period. All patients received thalidomide 50–100 mg/day for 12 months. Key outcomes—hospitalisation days, blood transfusions, and APC sessions—were recorded and compared before and after thalidomide therapy. Results Of 32 patients (22 men; mean age 55.53 ± 8.5 years), 78.1% had metabolic dysfunction–associated steatohepatitis (MASH)-related cirrhosis. Child-Pugh class distribution was A (46.9%), B (43.8%), and C (9.4%). Following thalidomide therapy, there were statistically significant reductions in mean hospitalisation days (7.66 vs 0.28; P < 0.001), mean transfusions (6.50 vs 0.16; P < 0.001), and mean APC sessions (2.66 vs 0.09; P < 0.001). Most patients (93%) received 50 mg/day dose with good tolerability. Conclusion Thalidomide demonstrates promising effectiveness for GAVE-related recurrent GI bleeding in cirrhotic patients. Its use was associated with significant reductions in hospitalisation, transfusion requirements, and endoscopic interventions, translating to meaningful clinical and health care resource benefits though larger confirmatory studies are needed.
