Introduction
Recent guidelines introduced the concept of metabolic dysfunction and alcohol-related liver disease (MetALD) and classify patients with heavy alcohol consumption as having alcohol-related liver disease (ALD), even in the presence of metabolic risk factors. Nevertheless, metabolic dysfunction may adversely affect outcomes in patients with ALD.
Aims & Methods
This retrospective single-center study aimed to evaluate the impact of metabolic dysfunction in patients with ALD within the broader spectrum of steatotic liver disease. Consecutive outpatients with chronic liver disease diagnosed with ALD, MetALD, or metabolic dysfunction–associated steatotic liver disease (MASLD) were included. Patients with ALD were further stratified into two groups: ALDm, defined by the presence of ≥2 metabolic risk factors, and ALDp, defined as pure alcohol-related disease. Primary endpoints were defined according to clinically significant portal hypertension (CSPH) status: fibrosis regression in patients without CSPH and liver-related adverse outcomes (LRAO) in those with CSPH. Significant fibrosis was defined as liver stiffness ≥8 kPa.
Results
A total of 590 patients were evaluated: 31.0% (n=183) had MASLD, 29.7% (n=175) had MetALD, and 39.3% (n=232) had ALD, including 128 patients with ALDm and 103 with ALDp.
The prevalence of significant fibrosis increased progressively across groups and was highest among patients with ALD (79.7%), followed by MetALD (69.7%) and MASLD (37.0%; p<0.001). Among patients with ALD, ALDm was independently associated with significant fibrosis compared with ALDp (OR 2.40; 95% CI 1.24–4.62; p=0.009).
In patients with ALD, improvement in metabolic risk factors independently predicted fibrosis regression (OR 5.19; 95% CI 1.28–21.08; p=0.021). Among those with CSPH, persistent metabolic dysfunction (HR 2.31; 95% CI 1.04–5.11; p=0.039), continued alcohol consumption (HR 2.31; 95% CI 1.04–5.11; p=0.039), and higher Child–Pugh score (HR 1.38; 95% CI 1.11–1.72; p=0.004) were independently associated with an increased risk of LRAO.
Conclusion
Metabolic dysfunction was independently associated with worse outcomes in patients with ALD. The authors propose a simple subdivision of ALD into ALDm and ALDp, thereby supporting the systematic assessment and management of metabolic risk factors even among heavy drinkers.
References
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO). "EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)." Obesity facts 17.4 (2024): 374-443.
Kumar, Ashish. "Introducing ‘ALD-Met’: bridging the Gap Between ‘MetALD’and ‘ALD’for heavy drinkers with metabolic dysfunction." Journal of Clinical and Experimental Hepatology 15.3 (2025).
