Non-alcoholic steatohepatitis

Abstract

Non-alcoholic steatohepatitis (NASH) has become recognized as a relatively common cause of abnormal liver function tests. It is defined by a combination of clinical features (excluding excess alcohol intake) and histopathological biopsy features which are indistinguishable from those of alcoholic hepatitis. The exclusion of excess alcohol intake is notoriously difficult and requires a combination of a good history supported by appropriate laboratory investigations, such as desialylated transferrin. There is marked large droplet fatty change as well as all or any of the features of alcoholic hepatitis, including Mallory's hyaline and neutrophils, although these tend to be less marked in NASH. NASH has been considered to be most common in obese, middle-aged females but recent studies have questioned this stereotype. The commonest clinical association is obesity and/or diabetes. Other associations include surgical and anatomical disorders predisposing to bacterial overgrowth as well as certain systemic disorders and drugs. NASH is usually a slowly progressive disorder with cirrhosis only seen in a minority of cases; in patients with large droplet fatty change alone the chances of progression are even less. The pathogenesis of NASH appears to be similar to that of alcohol excess. Both excess free fatty acids produce lipid peroxidation and increased cytokine production play significant roles. Like alcohol, obesity and/or diabetes can induce the cytochrome P450 system. Liver biopsy is indicated to assess the severity of the changes and to exclude other causes of liver disease. Treatment involves removal of the predisposing factors with drug treatments currently undergoing evaluation.