ACCELERATED PROGRESSION TO CIRRHOSIS AND HEPATIC DECOMPENSATION IN METALD AND ALD COMPARED TO MASLD: A GLOBAL STUDY

Introduction and Objectives

The natural history of MetALD remains poorly characterized. In a large global cohort, we compared the natural history of the main steatotic liver disease (SLD) subtypes in terms of liver fibrosis progression and hepatic decompensation.

Materials and Methods

Retrospective cohort study of adult participants with SLD (2003–2025), including MASLD, MetALD, and ALD according to the 2023 SLD criteria. Sociodemographic and clinical data, vibration-controlled transient elastography (VCTE) parameters, and liver biopsy (when available) were recorded. Other causes of liver disease were excluded. The primary outcome was progression to cirrhosis in those without cirrhosis at baseline (defined by 1. liver biopsy, or 2. VCTE ≥13.6 kPa, or Fibrosis-4 [FIB-4] >3.25 if other techniques were missing). Secondary outcomes included incidence of hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding, or hepatorenal syndrome). A multivariable Cox regression adjusted by age, sex, race, body mass index, diabetes, hypertension, hyperlipidemia, and smoking (for HCC) was performed.

Results

The total cohort included 150,306 participants from 15 countries; 87.5% MASLD, 7.9% MetALD, and 4.6% ALD. Overall, the median age was 61 years [IQR 51–70]; 52.8% men, and 97.6% Asian. At baseline, 12.2% of the cohort had a liver biopsy with F4 or a VCTE/FIB-4 suggestive of cirrhosis. During a median follow-up of 2.1 years [IQR 0.6–4.7], 0.9% of participants progressed to cirrhosis and 0.4% had hepatic decompensations. Individuals with MetALD and ALD exhibited a higher risk of progression to cirrhosis (MetALD aHR 1.34, 95%CI: 1.06–1.68, p=0.013; ALD aHR 1.82, 95%CI: 1.41–2.35, p<0.0001; MASLD: reference) and of hepatic decompensation (MetALD aHR 9.33, 95%CI: 6.32–13.75, p<0.0001; ALD aHR 20.56, 95%CI: 13.86–30.48, p<0.0001).

Conclusions

In this multi-ethnic global cohort, MetALD and ALD were associated with more rapid cirrhosis progression and greater decompensation rates than MASLD, independent of cardiometabolic factors.

Conflict of interest: None