Independent Predictors of Non-alcoholic Steatohepatitis (NASH) and Advanced Fibrosis in a Large Cohort of Patients with Non-alcoholic Fatty Liver Disease (NAFLD)

Abstract

Purpose: To assess the histologic and clinical predictors of NASH and fibrosis in patients with NAFLD. Methods: NAFLD patients from one outpatient liver clinic were included. All patients had clinical, demographic, laboratory data as well as liver biopsy slides. All liver biopsies were read by a single hepatopathologist. NASH was diagnosed with hepatic steatosis, ballooning degeneration of hepatocytes, lobular inflammation with or without Mallory-Denk bodies. Histologic fibrosis was graded from 0-4 (0-1 minimal fibrosis and >2 advanced fibrosis). T-Test and Chi-Square test are used for univariate analysis to compare the difference of individual numeric and categorical variables. Logistic regression is used to check if the association exists after considering the possible effect modification and confounding. Results: 523 NAFLD patients were included (Female: 77.6%, Caucasian: 75.0%, African-American: 17.0%, BMI: 46.6 +/- 10, Age: 44 +/- 11). Of these, 139 (26.4%) patients had biopsy-proven NASH and 138 (26.4%) had type 2 diabetes (DM). NAFLD patients with DM had higher serum glucose (p<.0001); serum triglycerides (p=0.043) but lower platelet count (p=0.0036). Diabetic NAFLD patients were most likely to be older (p<.0001), Caucasian (p=0.0285), have metabolic syndrome according to ATP-III criteria (p<0.0001) and more advanced fibrosis (p<0.0001). Patients with histologic NASH had higher serum AST, ALT and glucose as well as APRI score and advanced histologic fibrosis (p<0.0001). In multivariate analysis, male gender (OR, 95% CI): 2.216 [1.287, 3.814], presence of advanced fibrosis: 6.087 [3.537, 10.420], elevated AST: 1.30 [1.014, 1.046], lower HDL: 0.965 [0.944, 0.987] were independently associated with histologic NASH. NAFLD patients with advanced fibrosis were more likely to have higher AST, ALT, AST/ALT ratio, APRI (all p<0.0001) but lower platelet and serum HDL (p<0.05). These patients were older, more likely to be male, Caucasian, diabetic and histologic NASH (all p<0.0001). In multivariate analysis, having NASH: 4.926 [2.962-8.193], higher AST: 1.030 [1.009-1.052], lower platelet: 0.994 [0.990, 0.998] and being Caucasian: 1.884 [1.029, 3.453] were independently associated with advanced fibrosis. Conclusion: Components of metabolic syndrome, DM and elevated aminotransferases are associated with NASH and advanced fibrosis in NAFLD. These variables can be used to predict which NAFLD patients are most likely to develop adverse outcomes.