Lean non-alcoholic fatty liver disease is associated with increased all-cause mortality in the United States

Abstract It remains unclear whether lean non-alcoholic fatty liver disease (NAFLD) patients had worse outcomes. This study aims to investigate the long-term outcome of NAFLD in comparison to overweight and obese NAFLD using data from the National Health and Nutrition Examination Survey (NHANES) III. A total of 11860 participants (mean age, 43.4 years; 6498 [54.8%] women) were analyzed. NAFLD was assessed by hepatic ultrasonography and stratified into lean (body mass index, [BMI] < 25), overweight (BMI 25.0-29.9), and obese (BMI ≥ 30) subgroups. The Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations of NAFLD subgroups with risks of mortality. Lean NAFLD patients showed younger age and a lower prevalence of diabetes, hypertension, dyslipidemia, and insulin resistance. During a median follow-up period of 276 months, 3484 (29.4%) all-cause mortality occurred. All NAFLD subgroups were associated with increased all-cause mortality risk compared with healthy controls. However, only lean NAFLD was independently associated with all-cause mortality (HR, 1.23; 95% CI, 1.03–1.47) after the adjustment of confounders. This national-wide cohort study showed that lean NAFLD was significantly associated with higher all-cause mortality. A more granular assessment was needed to further characterize the phenotypes of the lean NAFLD population.