Severity of metabolic syndrome is greater among nonalcoholic adults with elevated ALT and advanced fibrosis

Abstract

The obesity epidemic has increased risk for nonalcoholic fatty-liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. We hypothesized that metabolic syndrome (MetS) severity would correlate with markers of NAFLD and NASH fibrosis. We evaluated cross-sectional data from 5463 participants of the National Health and Nutrition Examination Survey 1999-2012, age 20 to 64 years with and without diabetes, excluding those with heavy drinking and infectious liver serologies. We used linear and logistic regression to evaluate links between MetS-severity (using a race/ethnicity-specific MetS-severity-Z-score, MetS-Z) and apparent NALFD sequelae, using elevated alanine aminotransferase (ALT) to determine presence of NAFLD and elevated NAFLD Fibrosis Score to identify advanced fibrosis (NASH Clinical Research Network scoring stage 3-4). The prevalence of unexplained ALT elevations and advanced fibrosis were 11.4% and 1.37%, respectively. MetS-Z-scores were higher among those with elevated ALT (0.7, 95% confidence interval [CI]: 0.6, 0.8) and advanced fibrosis (1.7, CI: 1.5,1.9), compared to those without liver abnormalities (0.2, CI:0.2, 0.3). For every 1-standard-deviation unit increase in MetS-Z, there were higher odds of elevated ALT (OR = 1.58, CI: 1.44, 1.72) and advanced fibrosis (OR = 1.96, CI: 1.77, 2.18), with some attenuation after adjustment for age, sex, race/ethnicity, and diabetes status. Significant differences were noted by race/ethnicity, with stronger links among whites versus blacks. The degree of MetS-severity was associated with progressive increase in apparent NAFLD and advanced fibrosis; as MetS-severity has also been linked to future cardiovascular disease, diabetes, and chronic kidney disease, this provides support for use of a MetS-severity score to screen for general health, with high levels triggering further assessment for liver abnormalities.

Keywords: Fibrosis; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Risk.

Figure 1:

Inclusion and exclusion flow chart.

Figure 2:. MetS severity Z-score by liver categorization.

MetS-Z (means and 95% confidence interval) is shown for participants without liver abnormalities (normal), unexplained ALT elevations, advanced fibrosis (NAFLD Fibrosis Score >0.676).