Recompensation of decompensated cirrhosis in a spectrum of metabolic-dysfunction-related steatotic liver disease, with PEth-corroborated alcohol abstinence and modification of cardiometabolic risk factors

Background & Aims: Recompensation of decompensated metabolic-dysfunction-associated steatotic liver disease (MASLD) and Metabolic Dysfunction-Associated Steatotic Liver Disease with Alcohol Consumption (MetALD) cirrhosis remains unknown. Methods: We assessed rates and predictors of recompensation (Baveno VII criteria) and outcomes after modifiable interventions, including alcohol abstinence, dry weight loss, and cardiometabolic risk factor management, in a cohort of patients with decompensated MASLD/MetALD cirrhosis between October 2019 and March 2025. Results: Among 344 patients with steatotic liver disease-related cirrhosis (mean MELD-Na 14.7±3.6; MASLD-158, MetALD-186), 64(18.6%) achieved recompensation; MASLD (17.7%) and MetALD (19.4%), at a median of 15 months(IQR:14.5-15.5) over 3.9 years(IQR:2.8-4) follow-up. Baseline phosphatidylethanol (PEth) was negative in MASLD but positive in 69.4% of MetALD patients ( p =0.001). 61 patients (17.7%) died, 11(3.2%) underwent liver transplantation, and 5(1.5%) developed hepatocellular carcinoma. Mortality was lower in MASLD than in MetALD (12.0% vs. 22.6%; p =0.011). In competing risk regression adjusted for baseline MELD-Na, absence of large esophageal varices (sHR 1.97, 95%CI:1.22-3.99; p =0.021), weight loss ≥10% (sHR 7.42, 95%CI:3.15-17.47; p < 0.001), alcohol abstinence (sHR 1.87, 95%CI:1.29-3.32; p =0.003), and glycemic control (sHR 1.43, 95%CI:1.03-2.79; p =0.038) were associated with recompensation. Higher MELD-Na (sHR 1.13, 95%CI:1.06-1.2; p <0.001), MetALD etiology (sHR 1.87,95%CI:1.09-3.22; p =0.023), lack of recompensation( p <0.001), and ongoing alcohol consumption (sHR 5.3, 95% CI:2.85-9.74; p < 0.001) were associated with mortality. Conclusions: PEth improved the ascertainment of alcohol exposure and phenotyping of MASLD and MetALD. Weight loss ≥10%, achievement of glycemic control, and absence of large varices were independently associated with recompensation, which occurred in 18.6% of patients with decompensated MASLD/MetALD cirrhosis.