Advances in the treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world, and its prevalence is predicted to rise in the future in parallel with rising levels of obesity and type 2 diabetes mellitus. It is commonly associated with insulin resistance. Many patients have coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia, and are at increased risk of developing cardiovascular disease. Although patients with simple steatosis have a good prognosis, a significant percentage will develop nonalcoholic steatohepatitis which may progress to cirrhosis, end-stage liver failure and hepatocellular carcinoma. Despite promising results from several pilot studies and small to medium randomized controlled trials, there is currently no pharmacological agent that is licensed for the treatment of NAFLD. At present the mainstay of treatment for all patients is lifestyle modification using a combination of diet, exercise and behavioural therapy. With recent advances in the understanding of the pathogenesis of NAFLD, the goal of treatment has shifted from simply trying to clear fat from the liver and prevent progressive liver damage to addressing and treating the metabolic risk factors for the condition. To reduce liver-related and cardiovascular morbidity and mortality, all patients with NAFLD should be invited to enrol in adequately powered, randomized controlled studies testing novel therapies, many of which are targeted at reducing insulin resistance or preventing progressive liver disease. Coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia should be treated aggressively. Orlistat, bariatric surgery, angiotensin receptor blockers, statins, fibrates, metformin and thiazolidinediones should all be considered, but treatments should be carefully tailored to meet the specific requirements of each patient. The efficacy and safety of any new treatment, as well as its cost-effectiveness, will need to be carefully evaluated before it can be advocated for widespread clinical use.