Does Markedly Elevated ALT Correlate with the Presence of Steatohepatitis or Advanced Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease?

Abstract

Purpose: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and elevated liver enzymes. Currently, liver biopsy is required to assess for the presence of non-alcoholic steatohepatitis (NASH) and degree of fibrosis. While predictors of advanced fibrosis include increased age, obesity, AST/ALT ratio >1, insulin resistance and diabetes, there is still a need for a simple clinical predictor to evaluate for the presence of NASH in patients with steatosis. Our aim was to determine if marked elevation of ALT correlates with the presence of NASH or advanced fibrosis in patients with NAFLD. Methods: We conducted a chart review of outpatients, seen by our gastroenterology faculty practice between September 2000 and December 2008, with biopsy-proven NAFLD. Grading and staging of the liver biopsies were based on the Brunt et al. criteria (Am J Gastro 1999). Biochemical parameters were reviewed on all patients. Patients with coexisting liver disease and/or HIV were excluded. The upper limit of normal (ULN) ALT levels were defined as 19 U/L for women and 30 U/L for men (Ann Intern Med 2002). Advanced fibrosis was defined as presence of at least stage 3/4 fibrosis. Linear regression was used to compare ALT elevations (log (pt's level/ULN)) and AST/ALT ratios in patients grouped by biopsy results with and without controlling for age, sex, diabetes, and body mass index. Results: Of 46 patients with NAFLD (mean age 51.9 years; 65% male), 13 (28%) had ALT ≥ 4 × ULN, 33 (72%) had NASH, and 11 (26%) had advanced fibrosis. There was no association between ALT value and presence or absence of NASH or advanced fibrosis (Table 1; p > 0.4 in univariate and multivariate analysis). Advanced fibrosis was present in 6%, 25%, and 54% of patients with AST/ALT < 0.6, 0.6-0.8, or ≥ 0.8, respectively (Table 2; p<0.01).Table 1Table 2Conclusion: We found no relationship between the degree of elevation of ALT and presence of NASH or advanced fibrosis in patients with NAFLD. AST/ALT ratio is increased in patients with advanced fibrosis, as in other studies. Liver biopsy should be considered in patients with AST/ALT ratio >0.8. ALT alone is not predictive of the presence or absence of NASH and cannot guide the decision to biopsy a patient suspected of NAFLD.