Association of Components of Metabolic Syndrome and the Progression of Nonalcoholic Fatty Liver Disease

Abstract

Introduction: The effects of metabolic syndrome (MetS), its individual components, and baseline liver histology, on the rates of progression and regression of nonalcoholic fatty liver disease (NAFLD), were evaluated.

Methods: We conducted a post hoc analysis of a multicenter prospective cohort study using the noninterventional registry of the Nonalcoholic Steatohepatitis Clinical Research Network (2002-2022). We included patients aged 18 years or older with biopsy-proven NAFLD. Outcomes included progression/regression of histology defined by changes in NAFLD Activity Score, nonalcoholic steatohepatitis, or fibrosis. Crude incidence rates were compared among patients with MetS vs those without using Kaplan-Meier curves and log-rank test. Cox proportional hazard models were used to estimate effects of MetS and its components on the fibrosis progression/regression.

Results: We included 452 patients; the mean age was 51 years, one-third was male, and 85% was White. The median follow-up was 4.3 (range: 1-15.6) years. At baseline, patients with MetS, large waist circumference, and impaired glucose tolerance/diabetes had worse ballooning and fibrosis scores and a higher prevalence of definite nonalcoholic steatohepatitis than those without. MetS was not associated with fibrosis progression or regression. Impaired glucose tolerance/diabetes was associated with a higher risk of fibrosis progression (adjusted hazard ratio = 1.61; 95% confidence interval: 1.11-2.34) whereas hypertension was associated with a lower risk (adjusted hazard ratio = 0.64; 95% confidence interval: 0.43-0.96).

Discussion: In the cohort of patients with NAFLD, MetS was associated with greater histological severity at baseline but was not a risk factor of disease progression or regression. Impaired glucose/diabetes was associated with a higher rate and hypertension with a lower rate of fibrosis progression.

Keywords: disease progression; metabolic syndrome; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis.

Figure 1.

Kaplan-Meier curves of progression and regression by metabolic syndrome status. Fibrosis progression was defined as an increase of ≥1 point and regression as a reduction of ≥1 point on fibrosis score between biopsies. NASH progression was defined as the development of either borderline (among patients with no NASH at baseline) or definite NASH (among patients with no or borderline NASH at baseline), and regression as having no or borderline NASH at a follow-up liver biopsy (for patients with definite NASH at baseline) or having no NASH at follow-up (for patients with borderline NASH at baseline). Histological progression was defined as an increase by ≥2 points of NAS with ≥1 of which was increase in ballooning and regression as a decrease by ≥2 NAS points with ≥1 of which was decrease in ballooning and without worsening of fibrosis. NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, nonalcoholic steatohepatitis.