Lean fatty liver had milder histology but the same hard outcomes, and FIB-4 was weaker in it

Design

Multinational retrospective observational cohort, biopsy-confirmed

Population

18,326 adults with MASLD from 41 countries; 6.7% lean by BMI

Primary outcome

All-cause mortality and liver-related clinical events

Effect

Lean vs overweight/obese: mortality aHR 0.90 (0.69–1.16), events aHR 0.94 (0.76–1.17); elastography AUC 0.87 vs FIB-4 0.76 in lean

The Global MASLD project pooled 18,326 adults with biopsy-proven metabolic dysfunction-associated steatotic liver disease from 41 countries. 6.7% were lean by BMI, rising to about 11% in Asian centres.

Lean patients had less diabetes (38% against 48%), less advanced fibrosis (29% against 37%) and lower activity scores. Yet after adjustment they had no lower risk of death (aHR 0.90, 0.69–1.16) or of liver events such as cancer and decompensation (aHR 0.94, 0.76–1.17). What did predict outcome was fibrosis: F3–F4 was associated with about twice the mortality and more than three times the liver events. FIB-4 discriminated advanced fibrosis slightly less well in lean patients (AUC 0.76 against 0.79), while transient elastography did better (0.87 against 0.83).

The practical consequence is for the lean patient with type 2 diabetes and a fatty liver on ultrasound, who is often reassured because of their weight. This study suggests fibrosis assessment matters just as much in them, and that liver stiffness measurement is the more reliable test where it is available. It is a retrospective biopsy cohort, so patients were those already sent for biopsy and may be sicker than an unselected clinic population.

• Assess fibrosis in patients with type 2 diabetes and fatty liver whatever their weight; normal BMI is not reassurance.
• Where available, consider transient elastography rather than relying on FIB-4 alone in lean patients.
• Use waist circumference as well as BMI; the two agreed only moderately on who counted as lean.
• Expect lean MASLD more often in South Asian patients, where it was most common in this series.
• Refer or follow up on fibrosis stage, which tracked death and liver events far more closely than body size.

Why it matters

It challenges the habit of reassuring a slim patient with fatty liver; fibrosis, not weight, set their risk.

Don't overread it

This was a retrospective cohort of biopsied patients, so the absolute event rates may overstate risk in an unselected clinic.

The statistics, in plain English

An adjusted hazard ratio of 0.90 with a 95% interval of 0.69 to 1.16 crosses 1.0, meaning the data are consistent with lean patients having slightly lower, the same, or slightly higher risk — no meaningful difference either way. An area under the curve (AUC) measures how well a test separates people with and without advanced fibrosis: 0.5 is a coin toss, 1.0 is perfect, so 0.87 for elastography is good and 0.76 for FIB-4 is moderate.

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