Natural history in patients with normal or minimally elevated ALT

Abstract

Although serum alanine aminotransferase (ALT) has been used as a surrogate marker for liver diseases, its accuracy in reflecting liver damage has been questioned. This issue is further complicated by the recent challenge on the exact normal level of ALT. In studies examining the outcome of subjects with different ALT levels, it is found that ALT in the upper range of the traditionally defined normal levels is already associated with a higher risk of liver related complications and death. In the area of hepatitis B disease, many studies have confirmed by liver histology that a considerable proportion of patients with normal or minimally elevated ALT levels already have significant liver inflammatory and fibrotic activities. The most consistently found risk factors for significant fibrosis are male gender, increasing age and viral load (HBV DNA level). As far as the development of clinical complications of hepatitis B disease is concerned, patients with minimally elevated ALT levels are still at a considerable risk for the development of cirrhosis and hepatocellular carcinoma. Although this finding has been challenged for the ALT measurement to predict outcome being performed in a single time point, studies using median value and integration value of ALT levels over time during follow-up confirm that patients with minimally elevated ALT levels are at higher risk for development of liver related complications. Nevertheless, patients with persistently normal ALT (preferably men < 30; women < 19 U/L) do have a favourable prognosis.