Fatty liver disease may carry high mortality risk for those at normal weight

Fatty liver disease that occurs in people with normal body mass was associated with higher all-cause mortality, according to a systematic review and meta-analysis published today in Cureus Journal of Medical Science. This review also found higher mortality in three studies that compared fatty liver disease in lean people with those non-lean people, but researchers said the evidence for cardiovascular event risk and cardiovascular mortality was insufficient.

Steatotic (or fatty) liver disease is a serious disease that causes the liver to swell and can lead to cirrhosis, liver cancer and liver failure. It affects about a quarter to a third of adults worldwide, and cardiovascular disease is a major cause of morbidity and mortality among affected individuals. It is linked to Type 2 diabetes and other metabolic conditions such as obesity.

The American Liver Foundation estimates that between 1.5% to 6.5% of U.S. adults have MASH. A study published in JAMA Network Open in early 2025 projected that the number of cases in the U.S. could increase from 14.9 million in 2020 to 23.2 million in 2050.

Fatty liver disease in people with normal body mass index (BMI) is a small subset of those with metabolic dysfunction-associated steatohepatitis (MASH); it affects about 5% of the global population and is more prevalent in Asia.

In the Cureus study, researchers wanted to determine if lean steatotic liver disease carries a different mortality or cardiovascular risk. Researchers searched PubMed, Scopus, and the Cochrane Library through July 2026 for steatotic liver disease and cardiovascular and mortality endpoints. Of these, researchers included 15 studies for analysis, which were published between 2017 and 2026.

Of the 15 studies that were reviewed, five contributed adjusted hazard ratios for all-cause mortality. Across these five studies, steatotic liver disease that occurs in people with normal body mass was associated with higher all-cause mortality than comparator groups.

Five studies that researchers reviewed for this analysis had major adverse cardiac events (MACE) or composite cardiovascular outcomes as endpoints, but the endpoint definitions varied across the studies. The pooled estimates for cardiovascular outcomes show no statistically significant difference between the lean and non-lean patient groups. But researchers cautioned that this should be viewed with caution because of the differences in the studies assessed.

Only two studies reviewed looked at cardiovascular mortality and were not pooled for analysis.

The researchers speculated why those with MASH without obesity may have a higher risk of death. A loss of muscle mass, known as sarcopenia, is more frequent among those with normal BMIs and is also associated with frailty and mortality. Researchers cited one study that showed lower muscle mass and handgrip strength in lean patients than in overweight or obese patients with fatty liver disease.

Researchers also cited the possibility of malignancy, liver-related death, frailty, smoking-related disease or heavy alcohol use as other reasons for the higher risk of death among lean patients with MASH.

“This evidence does not support any specific screening interval, diagnostic pathway, or therapeutic intervention, none of which it can adjudicate. It does suggest that lean patients should not be triaged to lower-intensity metabolic or hepatic assessment on the basis of weight,” researchers wrote.

Researchers also point out that this analysis was done while nomenclature shifted for fatty liver disease to better reflect metabolic drivers and de-emphasize alcohol exclusion. Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) were coined in the 1980s to distinguish fatty liver disease that had causes other than drinking.

Metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated fatty liver disease (MAFLD) are now used to better align with cardiometabolic risk.