Long-term outcomes in lean and non-lean NAFLD patients: a systematic review and meta-analysis.

Background: Although nonalcoholic fatty liver disease (NAFLD) commonly occurs in overweight or obese individuals, it is increasingly being identified in the lean population. The association between lean and an increased risk of all-cause mortality among patients with NAFLD remains controversial. We aimed to perform a systematic review and meta-analysis of the literature to evaluate this association and compare the long-term outcomes of lean NAFLD patients and non-lean NAFLD patients.

Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, and Chinese Biomedical Literature Database (CBM) from inception to October 15, 2021, for relevant original research articles without any language restrictions. Our primary outcome was to compare the all-cause mortality in lean NAFLD patients and non-lean NAFLD patients by qualitative synthesis. Relative risks (RRs) and corresponding 95% confidential intervals (CIs) were pooled with a random effect model. Heterogeneity was evaluated using I-squared (I²) statistics while publication bias was determined using Egger's tests. Subgroup and sensitivity analyses were performed. As for secondary outcomes, we estimated total, cardiovascular, and liver-related mortality, as well as the incidence of diabetes, hypertension, cirrhosis, and cancer in lean and non-lean individuals with NAFLD by quantitative synthesis. Person-years of follow-up were used as the denominator to estimate the mortality and incidence.

Results: We identified 12 studies (n = 26,329), 7 of which (n = 7924) were used to evaluate the risk of all-cause mortality between lean and non-lean NAFLD patients. Lean patients with NAFLD were found to be at an elevated risk of death compared to non-lean patients (RR = 1.39, 95% CI 1.08-1.82, heterogeneity: I² = 43%). Among the lean NAFLD population, all-cause mortality was 13.3 (95% CI: 6.7-26.1) per 1000 person-years, 3.6 (95% CI: 1.0-11.7) for liver-related mortality, and 7.7 (95% CI: 6.4-9.2) for cardiovascular-related mortality. The incidence of new-onset diabetes was 13.7 (95% CI 8·2-22.7) per 1000 person-years, new-onset hypertension was 56.1 (95% CI: 40.2-77.9), cirrhosis was 2.3 (95% CI: 1.0-5.0), and cancer was 25.7 (95% CI: 20.3-32.4).

Conclusions: Lean patients with NAFLD had a higher risk of all-cause death than non-lean patients. Body mass index (BMI) should not be used as a criterion to determine whether further observation and therapy of patients with NAFLD are warranted.