30% with hepatic steatosis – but who is at risk? Defining Risk Factors for major liver-related Outcomes in patients with Metabolic Dysfunction- Associated Steatotic Liver Disease (MASLD)

Metabolic Dysfunction-Associated Liver Disease (MASLD) is characterized by fat accumulation in the liver and already affects nearly 30% of the population. Understanding who is at risk of major adverse liver outcomes (MALO) is crucial for developing preventive strategies.

Methods: 9,692 participants with MRI diagnosed liver steatosis were analyzed regarding their biochemical, genetic and lifestyle risk factors for MALO (n=26). Propensity Score Matching for sex, age and BMI was implemented in a 1:10 ratio.

Results: The strongest predictors for MALO were elevated alkaline phosphatase (m>129U/L, f>104U/L, OR=5.54 [2.35, 12.2]), elevated aspartate aminotransferase (m>50U/L, f>35U/L, OR=2.05 [0.87,4.49], all p<0.02). Arterial hypertension and type 2 diabetes were more common in the MALO group (OR=4.88 [2.19,11.9], OR=4.29[1.81, 9,55], p=0.003, p=0.047). Previously risky alcohol consumption increased MALO chances (OR=13.1 [3.8, 34.9], p<0.001). In the unmatched cohort Transmembrane 6 superfamily member 2 (TM6SF2) polymorphism rs58542926 was associated with MALO (OR=6.9 [1.07, 44.38], p=0.042), while patatin-like phospholipase domain containing 3 (PNPLA3) I148M was not.

Discussion: Readily available tools, like biomarkers, are effective for identifying patients at risk of MALO, who might need more frequent screening. Lifestyle interventions are useful even in late disease stages, as common comorbidities heavily impact the disease course. Previous alcohol consumption affects MALO occurrence, even after years of abstinence. Genetic testing for common polymorphisms connected to liver disease should be evaluated in MASLD patients. These risk factors might identify a group of MASLD patients that need more frequent attention.

Publication History

Article published online:
20 January 2025