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Background & Aims Metabolic Associated Fatty Liver Disease (MAFLD) was proposed as a better definition of Non-Alcoholic Fatty Liver Disease (NAFLD) to encompass the metabolic dysregulation associated with NAFLD. This redefinition challenges our understanding of the disease. Hence, this study sought to conduct an updated analysis of the prevalence, clinical characteristics and associated factors of MAFLD, with a further sensitivity analysis done based on lean and non-obese MAFLD individuals. Methods Medline and Embase databases were searched to include articles on MAFLD. Meta-analysis of proportions was conducted using the generalised linear mix model. Associating factors were evaluated in conventional pairwise meta-analysis with sensitivity analysis on lean and non-obese MAFLD. Results From pooled analysis involving 3,320,108 individuals, the overall prevalence of MAFLD was 38.77% (95%CI: 32.94% to 44.95%). 5.37% (95%CI: 4.36% to 6.59%) and 29.78% (95%CI: 26.06% to 33.79%) being of lean and non-obese respectively had MAFLD. Metabolic complications such as hypertension (OR: 2.63; 95%CI: 1.85 to 3.74; p<0.0001 and OR: 2.03; 95%CI: 1.74 to 2.38; p<0.0001, respectively) and diabetes (OR: 3.80; 95%CI: 2.65 to 5.43; p<0.0001 and OR: 3.46; 95%CI: 2.81 to 4.27; p<0.0001, respectively) were found as significant associating factors associated with lean and non-obese MAFLD. Conclusions This meta-analysis supports previous studies in reporting MAFLD to affect more than a third of the global population. While exploration of the pathogenic basis of fatty liver disease without metabolic dysregulation is required, the emphasis on management of concomitant metabolic disease in MAFLD can improve multidisciplinary efforts in managing the complex disease.

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Background and Aims The evaluation of the natural history of NASH has been limited. Currently, liver biopsy remains the gold standard in the assessment of NASH. Placebo‐controlled trials represent a controlled environment with paired biopsies for the evaluation of NASH. This meta‐analysis thus seeks to quantify the change severity of NASH over time, with patients on placebo arms from randomized controlled trials (RCTs) to examine the natural history of NASH. Methods A search was conducted to include NASH RCTs with placebo treatment arms. Primary outcomes were (1) the resolution of NASH without worsening of fibrosis, (2) two‐point reduction in NAFLD activity score without worsening of fibrosis, and (3) at least one‐point reduction in fibrosis. Generalized linear mix model was used to estimate pooled proportion and mean differences. Results This meta‐analysis of 43 RCTs included 2649 placebo‐treated patients. The pooled estimate of NASH resolution and two‐point NAFLD activity score reduction without worsening of fibrosis was 11.65% (95% CI: 7.98‐16.71) and 21.11% (95% CI: 17.24‐25.57). The rate of ≥1 stage reduction and progression of fibrosis was 18.82% (95% CI: 15.65‐22.47) and 22.74% (CI: 19.63‐26.17), respectively. Older age and African American ethnicity was associated with lower NASH resolution rate in placebo‐treated patients. Conclusions Despite the absence of any pharmacological interventions, a significant proportion of patients in the placebo arm demonstrated improvements in liver histology, highlighting the possibility that NASH is a disease that can not only progress but regress spontaneously over time. Additionally, histologic response in placebo‐treated patients is helpful in future design of phase 2B and phase 3 trials.

Background: Outcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.Methods: Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.Results: We screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14-1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23-3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30-3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24-3.07; P<0.01).Conclusions: Mortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.