Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank-order of the different pharmacological agents for both fibrosis regression and MASH resolution. Methods: We searched PubMed and Embase databases from 2020 to December 1, 2024, for published randomized-controlled trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking (SUCRA) curve analysis. Results: A total of 29 RCTs (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis. Conclusion: This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design. Export

Fatty pancreas disease (FPD) is a condition characterized by diffuse excessive intrapancreatic fat deposition with relevant metabolic implications but often overlooked by healthcare professionals. Our study aims to provide a comprehensive overview of the prevalence, clinical characteristics, and outcomes of FPD. PubMed and Embase databases were searched from inception to 10 April 2024. Pairwise meta-analysis was performed using the DerSimonian–Laird method. Meta-analysis of proportions was conducted using the inverse-variance method with logit transformation. Between-study heterogeneity was examined, with subsequent subgroup and meta-regression analyses, and publication bias was assessed. Eighteen studies with 111 682 individuals were included in this meta-analysis. The overall prevalence of FPD was 21.11% [95% confidence interval (CI): 11.04–36.58]. Diagnostic method influenced FPD prevalence (P < 0.01), with pooled prevalences of 17.53% (95% CI: 16.20–18.95), 30.05% (95% CI: 24.14–36.70), and 21.23% (95% CI: 8.52–43.88) for MRI, computed tomography, and transabdominal ultrasound, respectively. Patients with FPD were more likely to be older, have higher BMI, male, and have metabolic dysfunction. They also had an increased risk of metabolic syndrome, endocrine-related outcomes (i.e. diabetes and glycemic progression), and exocrine-related outcomes (i.e. acute pancreatitis and pancreatic cancer) compared with those without FPD. This study summarizes the epidemiology of FPD and highlights its clinical and prognostic significance. Increased multidisciplinary collaboration is needed to improve understanding of the disease and raise awareness among healthcare professionals. This study was a priori registered in International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024514116).