Cardiometabolic disorders, inflammation and the incidence of non-alcoholic fatty liver disease: A longitudinal study comparing lean and non-lean individuals

Ehimen C. Aneni, Gul Jana Saeed, Marcio Sommer Bittencourt, Miguel Cainzos-Achirica, Chukwuemeka U. Osondu, Matthew Budoff, Edison R. Parise, Raul D. Santos, Khurram Nasir

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3 Scopus citations


Background There is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals. Methods We analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (<150 minutes/week of moderate activity). We further assessed the risk of NAFLD with elevations in waist circumference and high sensitivity C-reactive protein (HsCRP). Results Over 15,580 person-years (PY) of follow-up, the incidence rate of NAFLD was 7.7 per 100 PY. In multivariate analysis adjusting for likely confounders, AD was associated with a 72% greater risk of NAFLD (IRR: 1.72 [95% CI:1.32–2.23]). Elevated blood glucose (IRR: 1.71 [95%CI: 1.29–2.28]) and physical inactivity (IRR: 1.46 [95%CI: 1.28–1.66]) were also independently associated with increased risk of NAFLD. In lean individuals, AD, elevated blood glucose and elevated BP were significantly associated with NAFLD although for elevated blood glucose, statistical significance was lost after adjusting for possible confounders. Physical inactivity and elevations in HsCRP were not associated with the risk of NAFLD in lean individuals only. Among lean (and non-lean) individuals, there was an independent association between progressively increasing waist circumference and NAFLD. Conclusion Cardiometabolic risk factors are independently associated with NAFLD. However, there are significant differences in the metabolic risk predictors of NAFLD between lean and non-lean individuals. Personalized cardiovascular disease risk stratification and appropriate preventive measures should be considered in both lean and non-lean individuals to prevent the development of NAFLD.

Original languageEnglish (US)
Article numbere0266505
Pages (from-to)e0266505
JournalPLoS ONE
Issue number4
StatePublished - Apr 2022


  • Alcoholism/complications
  • Blood Glucose
  • Body Mass Index
  • C-Reactive Protein
  • Humans
  • Hypertension/complications
  • Incidence
  • Inflammation/complications
  • Longitudinal Studies
  • Non-alcoholic Fatty Liver Disease/metabolism
  • Risk Factors

ASJC Scopus subject areas

  • General


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