Clinical spectrum and therapy of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease is increasingly being diagnosed worldwide and considered to be the commonest liver disorder in Western countries. It comprises a disease spectrum ranging from simple steatosis (fatty liver) through non-alcoholic steatohepatitis (NASH) to fat with fibrosis and, ultimately, cirrhosis. Simple steatosis is largely benign and non-progressive, whereas NASH can lead to cirrhosis, liver failure and hepatocellular carcinoma. Therapeutic strategies can be divided into those directed at components of the metabolic syndrome with potential beneficial liver effects and those directed specifically at the liver. Recent data suggest that diet and exercise improve NASH, particular in those achieving >7% weight loss. Obesity surgery has been shown to improve steatosis in all studies and inflammation and fibrosis in some. With respect to anti-diabetic drugs, results for metformin have not been convincing and concerns over the safety of glitazones have reduced the initial enthusiasm for their use. ACE inhibitors and angiotensin II receptor blockers hold the most promise as anti-hypertensive agents for patients with NASH and hypertension. With respect to more specific liver-directed therapies, there have been promising studies of antioxidants, including betaine and probucol, and vitamin E may improve NASH in adults and children. The TNF-α-lowering agent pentoxifylline may have beneficial effects on NASH. Liver transplantation is successful, but the disease recurrence rate is high in the absence of treatment of the underlying metabolic syndrome.