Liver Fat Is Associated With Markers of Inflammation and Oxidative Stress in Analysis of Data From the Framingham Heart Study

Clin Gastroenterol Hepatol. 2019 May;17(6):1157-1164.e4. doi: 10.1016/j.cgh.2018.11.037. Epub 2018 Nov 23.

Abstract

Background & aims: Nonalcoholic fatty liver disease is an inflammatory condition that results in progressive liver disease. It is unknown if individuals with hepatic steatosis, but not known to have liver disease, have higher serum concentrations of markers of systemic inflammation and oxidative stress.

Methods: We collected data from 2482 participants from the Framingham Heart Study (mean age, 51 ± 11 y; 51% women) who underwent computed tomography and measurement of 14 serum markers of systemic inflammation. Heavy alcohol users were excluded. The liver:phantom ratio (a continuous parameter of liver attenuation relative to a calibration phantom) was used to identify individuals with radiographic evidence of liver fat. Primary covariates included age, sex, smoking, alcohol, aspirin use, hypertension, dyslipidemia, diabetes, and cardiovascular disease. Body mass index and visceral fat were secondary covariates. We used multivariable linear regression models to assess the association between liver fat and systemic inflammatory markers.

Results: In multivariable-adjusted models, liver fat was associated with the following inflammatory markers: high-sensitivity C-reactive protein (P < .001), urinary isoprostanes (P < .001), interleukin 6 (P < .001), intercellular adhesion molecule 1 (P < .001), and P-selectin (P = .002). Additional adjustment for body mass index or visceral fat attenuated the results slightly, although all associations remained statistically significant (P for all ≤ .01).

Conclusions: In a community-based cohort, individuals with hepatic steatosis without known liver disease had higher mean serum concentrations of systemic markers of inflammation. Studies are needed to determine whether treatment of hepatic steatosis reduces systemic inflammation.

Keywords: Bomarkers; Cardiovascular Disease; NAFLD; Steatosis.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Body Mass Index
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Disease Progression
  • Female
  • Humans
  • Incidence
  • Inflammation / blood*
  • Intercellular Adhesion Molecule-1 / blood*
  • Intra-Abdominal Fat / metabolism*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multidetector Computed Tomography / methods*
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Oxidative Stress*
  • Prognosis
  • Risk Factors
  • United States / epidemiology

Substances

  • Biomarkers
  • ICAM1 protein, human
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein