NAFLD in Lean Patients May Be Linked to Metabolic Syndrome, Cardiovascular Risk

Microscopic photo of a professionally prepared slide demonstrating macrovesicular steatosis of the liver (fatty liver disease), hepatic steatosis, metabolic syndrome. Can be ssociated with nonalcoholic fatty liver disease (NAFLD) or Alcoholic Liver Disease (ALD). H&E stain.
Investigators aimed to determine the metabolic and cardiovascular phenotypes of lean patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) in lean patients is strongly associated with components of metabolic syndrome, namely glycemic dysregulation, and increased cardiovascular risks, according to study results published in Clinical and Translational Gastroenterology.

The pathophysiological mechanisms surrounding NAFLD in lean patients is still not well understood, leading to gaps in knowledge of risk stratifications and patient management. A team of researchers previously identified differences in glucose tolerance between lean patients with NAFLD and healthy individuals. In the present single-center, cross-sectional study, the investigators aimed to determine the metabolic and cardiovascular phenotypes of lean patients with NAFLD.

Between 2010 and 2020, patients with no chronic liver disease except NAFLD undergoing screening colonoscopy were assigned either cohort 1 (n=3043) or cohort 2 (n=1048) and were further assigned to either lean patients without NAFLD, lean NAFLD, overweight NAFLD (body mass index [BMI] 25-30 kg/m2), or obese NAFLD (BMI >30 kg/m2). In cohorts 1 and 2, NAFLD diagnosis was confirmed using ultrasound and controlled attenuation parameter, respectively. Calculated Framingham risk score was used to determine the 10-year cardiovascular risk.

The overall prevalence of NAFLD in cohorts 1 and 2 was 44.2% and 61.1%, respectively.

Compared with lean individuals without NAFLD (n=892), lean patients with NAFLD in cohort 1 (n=205) were more often men (P <.001), had a higher prevalence of visceral obesity (P <.001), dyslipidemia (P <.001), higher levels of triglycerides (P <.001), and lower levels of high-density lipoprotein cholesterol (P <.001). Results among cohort 2 members were similar for dyslipidemia and dysglycemia.  

Results from multivariable analyses suggested that lean patients with NAFLD were at greater risk for metabolic syndrome (adjusted odds ratio [aOR] for cohort 1, 4.27; P <.001; aOR for cohort 2, 2.97; P <.001), dyslipidemia (aOR for cohort 1, 2.22; P <.001; aOR for cohort 2, 2.24; P =.001), dysglycemia (aOR for cohort 1, 1.57; P =.017; aOR for cohort 2, 1.62; P =.035), and prediabetes (aOR for cohort 1, 1.52; P =.032; aOR for cohort 2, 1.61; P =.045).

Compared against lean patients without NAFLD, the median Framingham risk score was higher in both cohorts for lean patients with NAFLD (all P <.001) and was still higher in both cohorts 1 and 2 following multivariable analyses (P <.003 and P =.034, respectively).

“[W]e demonstrate a distinct cardiometabolic phenotype of lean NAFLD in 2 independent cohorts undergoing screening endoscopy, showing a strong association with prediabetes and 10-year cardiovascular risk,” the researchers noted.

“[F]uture studies are needed to further investigate the pathophysiological background but also to sharpen the definition of lean NAFLD and define algorithms for patient management,” the investigators concluded.


Semmler G, Wernly S, Bachmayer S, et al. Nonalcoholic fatty liver disease in lean subjects: associations with metabolic dysregulation and cardiovascular risk-a single-center cross-sectional study. Clin Transl Gastroenterol. 2021;12(4):e00326. doi: 10.14309/ctg.0000000000000326