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

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 multi-center prospective cohort study using the non-interventional registry of the nonalcoholic steatohepatitis (NASH) Clinical Research Network (2002-2022). We included patients ≥18 years with biopsy-proven NAFLD. Outcomes included progression/regression of histology defined by changes in NAFLD activity score, NASH or fibrosis. Crude incidence rates (IR) were compared among patients with MetS versus 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; mean age was 51 years, one-third was male, and 85% was White. 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 NASH than those without. MetS was not associated with fibrosis progression or regression. Impaired glucose tolerance/diabetes was associated with a higher risk for fibrosis progression (aHR=1.61; 95% CI: 1.11-2.34) while hypertension was associated with a lower risk (aHR=0.64; 95% CI: 0.43-0.96). Discussion: In the cohort of NAFLD patients, MetS was associated with greater histological severity at baseline but was not a risk factor for disease progression or regression. Impaired glucose/diabetes was associated with a higher rate and hypertension with a lower rate of fibrosis progression.