The study, led by Dr. Zhenyu Huo and colleagues from the Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China, analyzed long-term data from three major population-based cohorts: the UK Biobank, the Kailuan cohort, and the China Kadoorie Biobank. In total, data from 186,000 participants with MASLD were included, of whom about 5,000 were classified as lean. Lean MASLD was defined as a body mass index (BMI) below 25 kg/m² in the UK cohort and below 23 kg/m² in the two Chinese cohorts.
Over a median follow-up period of approximately 14 years, researchers tracked multiple health outcomes, including liver-related events (LREs), liver-related mortality, all-cause mortality, cardiovascular disease (CVD) mortality, hepatocellular carcinoma (HCC), and extrahepatic cancers.
The study led to the following notable findings:
- Lean individuals with MASLD had more than double the risk of liver-related events compared with non-lean MASLD patients (HR 2.14).
- Lean MASLD patients also had over twice the risk of liver-related mortality (HR 2.31).
- All-cause mortality was 26% higher in lean MASLD individuals (HR 1.26).
- Cardiovascular mortality increased by 22% among lean MASLD patients (HR 1.22).
- Risks of hepatocellular carcinoma and extrahepatic cancers were similar between lean and non-lean MASLD patients.
- Lean MASLD patients had a slightly lower risk of incident cardiovascular disease events (HR 0.89).
These findings indicate that while lean MASLD patients may appear metabolically healthier based on body weight, they are not protected from serious liver complications and, in fact, may have a worse hepatic prognosis than those with higher BMI. The mechanisms underlying this increased risk are not fully understood but may involve genetic susceptibility, altered fat distribution, or metabolic abnormalities that are independent of obesity.
Dr. Huo and colleagues highlighted that MASLD is not a benign condition, even among individuals with normal weight, emphasizing the need for clinicians to recognize and monitor this subgroup more closely. They noted that lean MASLD is often underdiagnosed, as traditional screening methods focus heavily on overweight and obese populations.
The study emphasizes that lean MASLD carries a substantially higher risk of liver-related morbidity and mortality despite lower overall body weight. While cardiovascular risks were slightly reduced, the markedly worse liver outcomes point to the need for early detection and targeted management strategies in lean individuals with MASLD.
The researchers call for greater clinical awareness and further studies to understand the biological mechanisms driving this distinct form of fatty liver disease.
Reference:
Huo Z, Chen Y, Huang Y, et alLong-term prognosis of lean MASLD: evidence from three population-based prospective cohortsGut Published Online First: 15 October 2025. doi: 10.1136/gutjnl-2025-336127
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