Lean NAFLD vs Nonlean NAFLD Presents Higher Risk for Liver-Related Mortality

Risk for liver-related death is more common among individuals with lean nonalcoholic fatty liver disease.

Patients with lean nonalcoholic fatty liver disease (NAFLD) demonstrated similar risk for all-cause and cardiovascular-related mortality and higher risk for liver-related mortality than nonlean patients with NAFLD, according to study findings published in Clinical Gastroenterology and Hepatology.

Obesity is a contributing risk factor for development of NAFLD. However, around 40% of patients with NAFLD do not have obesity and 20% have a lean body mass index (BMI). For the current study, lean NAFLD was defined as BMI less than 25 kg/m2.

Recent studies have reported inconsistent outcomes regarding mortality and liver-related events among patients with lean NAFLD, leading to lack of clarity about the clinical course of the disease.

To investigate, researchers conducted a systematic review and meta-analysis of studies published in PubMed, Embase, and Cochrane library databases from inception to May 2022 on mortality and cirrhosis among lean and nonlean patients with NAFLD. The analysis included 10 cohort studies (N=109,151) of patients with NAFLD (lean NAFLD; n=42,112 and nonlean NAFLD; n=67,039).

Clinical interventions should be considered for patients with lean NAFLD as intensively as for those with non-lean NAFLD.

When comparing mortality outcomes in patients with lean vs nonlean NAFLD, researchers discovered that patients with lean NAFLD had comparable all-cause mortality risks to patients with nonlean NAFLD (relative risk [RR], 1.09; 95% CI, 0.67-1.77) with pooled rates of all-cause mortality of 0.22% among patients with lean NAFLD and 0.15% among patients with nonlean NAFLD.

Compared with patients with nonlean NAFLD, patients with lean NAFLD also had similar risk for incidence of cardiovascular mortality (RR, 1.12; 95% CI, 0.66-1.90) and adverse liver events, including decompensated cirrhosis and hepatocellular carcinoma (HCC; RR, 0.81; 95% CI, 0.50-1.30).

The risk for liver-related mortality was higher among patients with lean NAFLD than nonlean NAFLD (RR, 1.88; 95% CI, 1.02-3.45) with pooled rates of 0.02% and 0.01% in lean and nonlean NAFLD groups, respectively. Compared with lean NAFLD, patients with overweight and NAFLD demonstrated significantly lower risk for liver-related mortality (RR, 0.38; 95% CI, 0.24-0.68), whereas risk among patients with obesity did not significantly differ from patients with lean BMI.

“Clinical interventions should be considered for patients with lean NAFLD as intensively as for those with non-lean NAFLD,” the study authors wrote. “Development of individualized treatment and preventive strategies is warranted, with further understanding of the pathophysiology underlying lean NAFLD.”

Study limitations include the observational design, significant heterogeneity among included studies, and the small number of included studies, which may lead to the inability to measure pooled effect sizes.


Ha J, Yim SY, Karagozian R. Mortality and liver-related events in lean versus non-lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. Published online November 25, 2022. doi:10.1016/j.cgh.2022.11.019