A retrospective study was performed to (1) characterize the clinical and histologic features of those with
nonalcoholic fatty liver disease (
NAFLD) and normal
alanine aminotransferase (ALT) values, (2) compare the spectrum of
NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of
NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with
NAFLD and normal ALT were identified and compared with 50 consecutive subjects with
NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained
hepatomegaly (n = 21) and evaluation as a potential donor for living donor
liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the
metabolic syndrome, the major risk factor for
NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of
NAFLD. A total of 12 subjects with normal ALT levels had bridging
fibrosis, whereas 6 had
cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced
fibrosis (bridging
fibrosis or
cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal
fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced
fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of
NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying
steatohepatitis with advanced
fibrosis.