Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values.

Non-alcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is a well-established cause for chronic liver disease. In most studies on NASH, elevation in alanine aminotransferase (ALT) is taken as one of the diagnostic criteria. However, the clinical and histological spectrum and natural history of NAFLD with normal ALT are not well explored. This study was planned to define the clinical spectrum and natural history of patients with NAFLD with normal ALT, and to compare them with NAFLD with abnormal ALT. A prospective study including 81 consecutive patients with ahistological diagnosis ofNAFLD was planned during the period from 1999 to 2003. Consecutive (n=81) patients with the histological diagnosis of NAFLD were included in the study. In all the patients, clinical, anthropometric, laboratory, histological and imaging features were noted at the baseline. All these patients were followed up regularly at 6-month intervals. Of the 81 cases, 25 patients (including 60% cirrhotics) had persistently normal enzyme, whereas 56 (including 23% cirrhotics) had abnormal ALT. Both the groups were comparable with respect to distribution of age, gender, ethnicity, clinical features, imaging features, histological severity and laboratory features; except a higher incidence of diabetes and higher occurrence of advanced liver disease at baseline in NAFLD with normal ALT. Natural history of NAFLD was better in patients without cirrhosis irrespective of baseline ALT levels than in patients with cirrhosis; except for a higher incidence of decompensation in cirrhotics with normal ALT. The entire clinical and histological spectrum of NAFLD is seen in patients with normal ALT and is not different from patients with abnormal ALT. In patients with diabetes and hepatomegaly in the absence of other obvious liver diseases, even normal ALT may not rule out advanced liver disease, and liver biopsy may be necessary to identify the severity of liver disease.