Nonalcoholic Fatty Liver Disease

Pouneh S. Mofrad, MD, Arun J. Sanyal, MD


April 16, 2003

In This Article


As discussed above, gradual weight loss should be advocated in overweight individuals.[28] Weight reduction by 10% or more has been associated with normalization of elevated serum ALT levels and with a decrease in hepatomegaly.[29,30,31] It should be reiterated that rapid weight loss may cause progression of NAFLD. A heart-healthy diet, as recommended by the American Heart Association and American Diabetes Association, appears to be a reasonable recommendation in patients with NAFLD.[32,33] The effects of pharmacologic agents used to induce weight loss (eg, orlistat) on liver histology are not well known. The decision to use such agents or to proceed to bariatric surgery should be dictated by the degree of obesity, the presence of other end-organ damage, and the potential for severe hepatic decompensation due to surgery or rapid weight loss, as dictated by National Heart, Lung, and Blood Institute guidelines for weight management.[28]

Patients with diabetes should have their disease controlled appropriately. The impact of glycemic control and the type of antidiabetic therapy on liver histology in patients with diabetes and NASH are not known. Because NAFLD is associated with insulin resistance, it makes theoretical sense to use an insulin-sensitizing agent in diabetic patients who also have NAFLD. The risks of hepatotoxicity associated with these agents have not yet been well characterized in this population and, if these agents are used, patients must be educated regarding the potential risks of hepatotoxicity and monitored according to US Food and Drug Administration guidelines.

Diabetic medications that have been shown to correct insulin resistance may prove to be beneficial in treating patients with NAFLD, even in the absence of overt diabetes, because most of these patients have underlying insulin resistance. Metformin, a biguanide, has been shown to improve serum aminotransferase levels in a recent study. The thiazolidinediones (eg, pioglitazone) act as peroxisome proliferator-activated receptor (PPAR)-gamma agonists and improve peripheral insulin sensitivity. A small study of patients treated with troglitazone showed improvement in mean ALT levels and in hepatocellular inflammation. Two small pilot studies of rosiglitazone and pioglitazone, published only in abstract form, have also shown promising results.[34,35] However, there are no definitive data regarding the use of these drugs in the treatment of NAFLD, and the use of such agents should therefore be considered experimental at this time.

Several hepatoprotective drugs have also been used in patients with NAFLD ( Table 8 ). These agents include vitamin E, ursodeoxycholic acid, lecithin, beta-carotene, taurine, selenium, and betaine. In a small study,[36] taurine was given to obese children with fatty liver. The investigators reported a decrease in ALT levels in these patients, leading to the conclusion that taurine has hepatoprotective effects. However, this study, as well as most other studies, is limited by the lack of histologic data.

Several large-scale trials using these agents are currently under way.