Metabolic dysfunction-associated steatotic liver disease (MASLD) is often linked to obesity, but new research suggests that even lean people with fatty liver disease may fare worse over time. Findings presented at the AASLD Liver Meeting show that non-obese people with MASLD had high rates of liver-related complications and death, underscoring the need to rethink how risk is assessed and managed in this population.

MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), are responsible for a growing proportion of advanced liver disease worldwide. Over time, the buildup of fat in the liver can lead to serious complications, including fibrosis, cirrhosis and liver cancer. Fatty liver disease often occurs in people with obesity, type 2 diabetes and other metabolic conditions. With only two approved medications (Rezdiffra and Wegovy), management still largely depends on lifestyle changes such as weight loss and exercise.

Abdellatif Ismail, MD, of Cleveland Clinic Florida, and colleagues looked at liver-related events and mortality among 939,848 people with hepatic steatosis (liver fat accumulation) and at least one cardiometabolic risk factor using data from the TriNetX U.S. Collaborative Network. The research team compared outcomes over a 10-year period for 121,612 people of normal weight, defined as a body mass index (BMI) of 24.9 or lower, and 818,236 people with obesity, defined as a BMI of 25.0 or higher.

Compared to people with obesity, those without obesity had a higher risk for cirrhosis (3.6% versus 4.4%), liver-related events (3.7% versus 7.1%), hepatocellular carcinoma (0.6% versus 0.9%) and liver transplantation (0.3% versus 0.5%). What’s more, the lean group also had higher cardiovascular-related mortality (1.0% vs. 1.7%) and all-cause mortality (7.1% versus 14.3%).

“Our findings showed that lean (non-obese) patients with MASLD have worse liver-related events, cardiovascular mortality and all-cause mortality compared to obese patients with MASLD,” wrote the researchers. “This is consistent with the notion that lean individuals with MASLD may have more pronounced metabolic dysfunction leading to a higher risk of progression to advanced fibrosis, cirrhosis and cardiovascular disease compared to their obese counterparts with similar degrees of steatosis.”

Based on these findings, the researchers suggest that using other anthropometric measures besides BMI, including waist circumference, could help better establish cardiometabolic risk factors for people with MASLD.

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