Research Summary

Fibrosis Severity Linked to Prognosis in Lean MASLD

Edited by:
Ashton L. Stahl

Key Highlights

  • Among 18,326 adults with biopsy-confirmed metabolic dysfunction–associated steatotic liver disease (MASLD), 6.7% were lean by body mass index.
  • Lean patients had less advanced fibrosis, but lean status was not independently associated with mortality or clinical events.
  • Liver stiffness measurement showed greater accuracy than the Fibrosis-4 score for identifying advanced fibrosis in lean patients.

Patients with lean metabolic dysfunction–associated steatotic liver disease (MASLD) had milder histologic disease but no significant difference in clinical outcomes compared with patients with overweight or obesity, according to a study published in JAMA. Fibrosis severity, rather than lean status, was associated with prognosis.

The researchers conducted a multinational, retrospective observational study of adults with biopsy-confirmed MASLD from 41 countries participating in the Global MASLD project. They defined lean status using body mass index (BMI) and waist circumference and evaluated all-cause mortality and clinical events, including hepatocellular carcinoma, hepatic decompensation, liver transplant, and death. They also assessed the accuracy of the Fibrosis-4 (FIB-4) score and liver stiffness measurement (LSM) by transient elastography for identifying advanced fibrosis.

Study Findings

The cohort included 18,326 patients with a mean age of 50.9 years; 47.6% were male. Overall, 6.7% were lean by BMI. Among 12,202 patients with available waist circumference measurements, 6% were lean by that measure. Lean MASLD was most prevalent in Asia.

Compared with patients with overweight or obesity, lean patients had lower prevalences of type 2 diabetes (38.2% vs 48.3%) and advanced fibrosis (29.3% vs 37.2%). Mean Non-Alcoholic Fatty Liver Disease Activity Scores were also lower (3.96 vs 4.41).

For identifying advanced fibrosis, FIB-4 had an area under the curve of 0.76 in lean patients vs 0.79 in patients with overweight or obesity. Corresponding LSM values were 0.87 and 0.83.

Unadjusted all-cause mortality rates were 1.08 vs 0.91 per 100 person-years in lean patients and those with overweight or obesity, respectively. Clinical event rates were 1.51 vs 1.43 per 100 person-years. Lean status was not independently associated with mortality (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.69-1.16) or clinical events (aHR, 0.94; 95% CI, 0.76-1.17).

Advanced fibrosis, however, was associated with higher risks of mortality (aHR, 2.10; 95% CI, 1.71-2.57) and clinical events (aHR, 3.41; 95% CI, 2.90-4.03).

Clinical Implications

According to the study authors, lean MASLD represents a distinct phenotype with milder histologic disease but similar clinical outcomes compared with MASLD in patients with overweight or obesity. The authors identified fibrosis severity as the prognostic factor and reported that LSM provided more accurate risk stratification than FIB-4 in lean patients.

Expert Commentary

“Fibrosis severity, rather than body composition, was associated with prognosis and LSM was reliable in lean individuals,” the researchers concluded.

Reference

de Avila L, AlNaamani KM, Papatheodoridi M; the Global MASLD Study Investigators on behalf of the Global NASH/MASH Council. Histologic features and clinical outcomes of lean metabolic dysfunction–associated steatotic liver disease. JAMA. Published online September 30, 2026. doi:10.1001/jama.2026.18491