Abstract

Introduction: While obesity is highly contributory to the development of nonalcoholic fatty liver disease (NAFLD), around 40% of patients with NAFLD are non-obese or lean. However, clinical outcomes of lean NAFLD are not well described, and the magnitude of the risk of mortality in lean patients with NAFLD compared to those who are non-lean remains uncertain. Methods: PubMed, Embase, and Cochrane library database were searched from inception to May 28, 2022 to identify eligible cohort studies assessing the risk of mortality among lean and non-lean patients with NAFLD. Meta-analysis was performed using random-effects models to obtain pooled relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity between studies was calculated using the Cochran Q test and I statistics. Results: Ten cohort studies with 109,151 patients with NAFLD were included. Patients with lean NAFLD had a comparable risk of all-cause mortality (RR, 1.09; 95% CI, 0.67 to 1.77; I-squared, 97.7%) and cardiovascular disease-specific mortality (RR, 1.12; 95% CI, 0.66 to 1.90; I-squared, 86.2%) to those with non-lean NAFLD. The pooled risk of liver disease-specific mortality was 1.88 times (RR; 95% CI, 1.02 to 3.45; I-squared, 29.4%) higher in patients with lean NAFLD. Conclusion: In patients with NAFLD, lean individuals have a higher risk of liver disease-specific mortality than non-lean individuals, however, the risk of all-cause mortality and cardiovascular mortality did not differ among the two groups. Further understanding of the risk factors, genetic and ethnic variabilities, and metabolic process of lean NAFLD phenotype is warranted. Furthermore, research is needed to determine mechanisms on how lean NAFLD is associated with worse liver mortality and to develop individualized treatment strategies for patients with lean NAFLD.Figure 1.: Comparative risk of all-cause mortality in lean and non-lean patients with NAFLD.

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