Lean Patients at Similar Risk for Poor Outcomes, Mortality as Patients Classified As Non-Lean With NAFLD

A nutritionist doctor measures the body of a male patient with a measuring tape on adipose tissue and excess weight. belly slimming diet, individual food
Investigators assessed baseline characteristics and long-term outcomes of White patients classified as lean with nonalcoholic fatty liver disease.

White patients with nonalcoholic fatty liver disease (NAFLD) progress to advanced liver disease at a similar rate, regardless of body mass index (BMI), indicating that a BMI-driven approach may not be supported by evidence. These findings were published in the journal Gut.

White patients (N=1339) with biopsy-confirmed NAFLD were recruited at multiple sites in Italy, Spain, the United Kingdom, and Australia from 1990 to 2016. Liver and nonliver outcomes were assessed on the basis of lean (BMI, <25 kg/m2) and non-lean (BMI, ³25 kg/m2) status.

The patient population was aged median 48 (IQR, 38-57) years, BMI was 29.8 (IQR, 26.5-34.5) kg/m2, and 28.2% had diabetes. The lean (14.6%) group was significantly younger and included more men; fewer patients in the lean cohort had diabetes, they had smaller waist circumferences, higher total bilirubin and low-density lipoprotein cholesterol, and lower glucose and triglycerides (all P £.03). The BMI cohorts had a similar distribution of risk loci genotypes.

Histologically, fewer of the lean cohort patients had steatosis, lobular inflammation, ballooning, advanced liver fibrosis, and nonalcoholic steatohepatitis (all P £.001).

At a median follow-up of 92 months, among the lean and non-lean cohorts, new-onset diabetes occurred among 90/785 and 11/177 (adjusted hazard ratio [aHR], 1.55; 95% CI, 0.83-2.9; P =.171), cardiovascular events among 122/1083 and 14/192 (aHR, 1.3; 95% CI, 0.73-2.2; P =.39), extrahepatic cancers among 93/1076 and 17/191 (aHR, 0.42; 95% CI, 0.39-1.4; P =.44), liver-related events among 88/1137 and 9/193 (aHR, 1.4; 95% CI, 0.7-2.7; P =.39), and hepatocellular carcinoma among 29/1136 and 2/192 (aHR, 1.9; 95% CI, 0.46-8.1; P =.37) patients, respectively.

Deaths occurred among 53 individuals, 5 of whom were part of the lean cohort. Mortality did not differ significantly on the basis of lean status (P =.069); however, when stratified by obesity status the difference was significant (P =.021).

The only identified predictor for mortality was fibrosis stage 3 to 4 (HR, 7.4; 95% CI, 1.3-41.3; P =.022).

These findings may not be generalizable, as the majority of patients with lean NAFLD were recruited in Italy and some underlying heterogeneity may have biased these results.

These data indicate that patients who had lean NAFLD did not have decreased risk for poor clinical outcomes and mortality compared with patients classified as non-lean. Lean patients should not be overlooked when considering disease management and inclusion in clinical trial research.


Younes R, Govaere O, Petta S, et al. Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach? Gut. 2022;71(2):382-390. doi:10.1136/gutjnl-2020-322564