Global prevalence, metabolic characteristics, and outcomes of lean-MAFLD: a systematic review and meta-analysis.

Background: Metabolic Dysfunction-Associated Fatty Liver disease (MAFLD) among lean individuals is increasingly recognized. We aimed to compare the prevalence, metabolic characteristics, and outcomes of lean vs overweight/obese-MAFLD patients.

Methods: Databases of Embase, Medline, and Web of Science were searched from inception till October 2023. Only cohorts adhering to the lean-MAFLD criteria as defined by the international consensus statement were included.

Results: In the pooled analysis of 10,013,382 individuals, the prevalence of lean-MAFLD in the general population was 1.94% (95% CI 1.10-3.39%, I² = 98.7%). Lean and overweight/obese-MAFLD patients had similar metabolic characteristics for blood pressure, LDL, TG, blood glucose, and HbA1c. There was an increased incidence rate and likelihood for liver-related mortality for lean-MAFLD vs overweight/obese-MAFLD [1.33 per 1000 patient-years (95% CI 1.28-1.39) vs 0.76 (95% CI 0.25-2.28), (OR 3.56 (95% CI 3.45-3.67), p < 0.01). There were similar incidence rates and odds ratios between lean vs overweight/obese-MAFLD for: (1) all-cause mortality [10.08 per 1000 patient-years (95% CI 9.93-10.23) vs 8.94 per 1000 patient-years (95% CI 4.08-19.57), (OR 1.92 (95% CI 0.01-220.57), p = 0.33)]; (2) cardiovascular-related mortality [2.53 per 1000 patient-years (95% CI 0.65-9.96) vs 2.07 per 1000 patient-years (95% CI 0.80-5.39), (OR 1.91 (95% CI 0.02-142.76), p = 0.58)]; and (3) cancer-related mortality [3.42 per 1000 patient-years (95% CI 3.33-3.51) vs 3.15 per 1000 patient-years (95% CI 1.21-8.19), (OR 1.99 (95% CI 0.29-13.52), p = 0.13).

Conclusion: Lean-MAFLD patients have an equivalent metabolic burden compared to overweight/obese-MAFLD patients and thus a similar incidence rate of major extrahepatic complications. However, they have an increased risk of liver-related mortality.