Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD)

Background: Non-alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non-alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD.

Aim: To determine ALT value that will accurately predict NASH and advanced fibrosis using area under the receiver operating characteristics curve (AUROC) analysis.

Methods: Demographic, clinical and laboratory data of an ethnically diverse cohort of biopsy proven NAFLD patients were retrospectively analysed under univariate and multivariate analyses. Liver biopsies were scored using NASH clinical research network (NASH CRN) system. AUROC were performed for NAFLD Activity Score ≥5 (NASH) and fibrosis score ≥2 (advanced fibrosis).

Results: Two hundred and twenty-two patients were analysed. Fifty six (23%) had normal ALT. There was no difference in the rate of advanced fibrosis between normal and elevated ALT (26.8% vs. 18.1%, P = 0.19). However, significantly lower percentage of normal ALT group had NASH compared with elevated ALT group (10.7% vs. 28.9%, P < 0.01). Overall, 37.5% of normal ALT group had NASH or advanced fibrosis, whereas 53% of elevated ALT had no NASH or advanced fibrosis. Higher ALT values correlated with higher specificity, but lower sensitivity for both NASH and advanced fibrosis. AUROC for ALT level correlating NASH and advanced fibrosis were 0.62 and 0.46 respectively.

Conclusion: There is no optimal ALT level to predict NASH and advanced fibrosis. Metabolic risk factors should be evaluated to select patients for a liver biopsy to confirm NASH and advanced fibrosis.