Liver and cardiovascular outcomes in lean non-alcoholic fatty liver disease: an updated systematic review and meta-analysis of about 1 million individuals

Non-alcoholic fatty liver disease (NAFLD) is present in lean people. However, the magnitude of the prognostic hepatic and cardiovascular risk in these patients compared to non-lean counterparts remains unclear. We aimed to investigate this topic, and to explore whether these risks change based on factors related to NAFLD severity.

PubMed and Embase databases were searched for cohort studies (published through April 2024) that evaluated liver and cardiovascular (CV) outcomes in lean and non-lean individuals with NAFLD and reported unadjusted or adjusted data. We pooled risk ratios (RRs) or hazard ratios (HRs) using a random-effects modeling and performed subgroup and meta-regressions analyses.

We identified 22 studies with over 1 million NAFLD patients (13.0% were lean). Lean NAFLD showed a similar risk of liver-related events in unadjusted analysis (RR 1.08, 95% CI 0.79–1.49, I² = 31%), but a higher risk in adjusted analysis (HR 1.66, 95% CI 1.17–2.36, I² = 83%) compared to non-lean NAFLD. Lean NAFLD had a higher risk of liver-related mortality (RR 2.22, 95% CI 1.57–3.15, I² = 0%; HR 2.26, 95% CI 1.14–4.51, I² = 0%). For CV outcomes, lean NAFLD had a lower risk of any cardiovascular disease in unadjusted analysis (RR = 0.82, 95% CI 0.70–0.95, I² = 88%), but similar risk in adjusted analysis (HR 0.89, 95% CI 0.77–1.02, I² = 78%), and similar risk of cardiovascular mortality (RR 1.09, 95% CI 0.71–1.66, I² = 85%; HR 1.26, 95% CI 0.89–1.78, I² = 46%) compared to non-lean NAFLD.

Lean NAFLD patients have worse liver outcomes, but similar CV outcomes compared to non-lean NAFLD patients, highlighting the importance of monitoring both groups closely.