Increasing metabolic co-morbidities are associated with higher risk of advanced fibrosis in nonalcoholic steatohepatitis

by Robert J. Wong, Tram Tran, Harvey Kaufman, Justin Niles, Robert Gish

Hepatic fibrosis and advanced fibrosis in particular is the strongest predictor of liver-related outcomes and mortality among nonalcoholic steatohepatitis (NASH) patients. Understanding prevalence and predictors of NASH with advanced fibrosis is critical for healthcare resource planning. Using a large U.S. clinical laboratory database from 10/1/2017-9/30/2018, adults negative for hepatitis B and hepatitis C and after excluding for alcoholic liver disease and pregnancy were evaluated for prevalence of F3 and F4 fibrosis using a systematic algorithm of five fibrosis-4 (FIB-4) criteria: Criteria 1 (≥F3: >2.67), Criteria 2 (2.674.12), Criteria 3 (2.673.15), Criteria 4 (3.253.5), Criteria 5 (3.254.12). Metabolic co-morbidities evaluated included decreased high density lipoprotein (<40 mg/dL men, <50 mg/dL women), high triglycerides (≥150 mg/dL), elevated hemoglobin A1C (≥6.5%). Parallel analyses of patients with specific NAFLD/NASH ICD-9/10 codes from 10/1/2013-9/30/2018 were performed. Multivariate logistic regression models evaluated for predictors of ≥F3 fibrosis. Among patients with NAFLD/NASH ICD-9/10 codes, ≥F3 prevalence ranged from 4.35% - 6.90%, and F4 prevalence ranged from 2.52%– 3.67%. Increasing metabolic co-morbidities was associated with higher risk of ≥F3 fibrosis. Compared to NASH patients without metabolic co-morbidities, NASH with four concurrent metabolic co-morbidities had higher risk of ≥F3 (OR 1.56, 95% CI 1.40–1.73, p<0.001). In summary, prevalence of NASH with advanced fibrosis among U.S. adults was as high as 6.90% and prevalence of NASH with cirrhosis was as high as 3.67%, representing 5.18 million and 2.75 million, respectively, when using an estimate of 75 million U.S. adults with NAFLD. Co-morbid metabolic abnormalities were associated with higher risk of advanced fibrosis among NASH patients.