New treatments for nonalcoholic fatty liver disease.

The majority of patients with nonalcoholic fatty liver disease are overweight and obese, lead relatively sedentary lifestyles, and have underlying insulin resistance. Treatment aimed at improving body weight and activity should be the cornerstone of our therapeutic armamentarium in combating this disease. Evidence suggests that diets low in processed carbohydrates and saturated fats with a goal to achieve a 500- to 1000-calorie/day deficit improve insulin sensitivity, reduce serum aminotransferases, and decrease hepatic steatosis. Encouragingly, improvements are seen with as little as a 5% reduction in body weight. Histopathologic parameters of steatohepatitis also appear to improve with weight loss. Antioxidant supplementation, specifically with vitamin E, may be considered as adjunctive therapy. Other antioxidants and the thiazolidinediones (pioglitazone and rosiglitazone) appear to be efficacious, but larger confirmatory studies are needed to ensure they are safe and beneficial in patients with nonalcoholic steatohepatitis. Novel agents such as renin-angiotensin system inhibitors may eventually prove to be efficacious as well. Future treatment for patients failing to achieve weight loss goals is likely to consist of combination therapy targeting insulin resistance, oxidative stress, and fibrogenesis.