Rising obesity rates boosting liver disease risk: the typical patient with nonalcoholic fatty liver disease has a BMI above 30 and insulin resistance.

NEW ORLEANS -- Fatty liver disease and nonalcoholic steatohepatitis have become increasingly common with rising obesity rates, Dr. Eugene R. Schiff said at the annual meeting of the American College of Physicians.

Nonalcoholic fatty liver disease (NAFLD) can have many causes, including nutritional deficiencies, drugs, and toxins, but today's typical patient has a body mass index above 30, high triglycerides, insulin resistance, and, in many cases, frank type 2 diabetes along with elevated liver enzymes. The same phenomenon also can occur in patients with BMIs below 30 who have recently gained a lot of weight or who have high waist/hip ratios, he said.

This clinical picture is "one of the biggest problems I see right now." said Dr. Schiff, professor of medicine and chief of the division of hepatology at the University of Miami.

The liver disease in these patients can fall anywhere in the spectrum from simple NAFLD all the way to nonalcoholic steatohepatitis (NASH), in which histologic findings range from fat plus ballooning degeneration to fat plus alcoholic hepatitis-like lesions that are impossible to distinguish from those of alcoholic liver disease. Dramatic increases in obesity in recent years have brought both greater rates of NAFLD and of progression to NASH.

In patients who fit the clinical profile, the diagnosis is made by asking whether and how much alcohol they drink and by obtaining the ratio of AST to ALT. In NAFLD, both are elevated, while in alcoholic liver disease the AST value is about twice that of ALT, Dr. Schiff said.

Ultrasound imaging can help determine whether fatty liver is present, but it's not specific enough for diagnosis of NAFLD or NASH. CT and MRI are equally nonspecific, but they are a bit more sensitive than ultrasound and can give information about the shape of the liver and size of the spleen. In NAFLD/NASH, the liver is significantly more radiolucent than the spleen; the two are about equally dense in a normal liver. (If the liver is denser than the spleen, iron overload is the most likely diagnosis.)

Current treatment is aimed at reducing the insulin resistance. Weight loss, if patients can achieve and maintain it, will usually reverse the transaminase abnormalities.

Drug therapy presents a conundrum, since the two currently available classes of insulin-sensitizing agents, metformin and the glitazones, are contraindicated in patients with liver disease. So are the statins, which is a problem because most of these patients are hyperlipidemic. Still, it's hard to avoid using those three agents in diabetic patients, so close monitoring of liver enzymes is critical, Dr. Schiff noted.

Other treatments are under investigation. Betaine, a naturally occurring metabolite of choline, reduced aminotransferase levels in a 1-year pilot study of 10 adult patients with NASH. It also produced marked improvements in steatosis, necroinflammatory grade, and stage of fibrosis with no significant safety problems.

The investigators recommended further evaluation in a randomized, placebo-controlled trial (Am. J. Gastroenterol. 96[9]:2711-17, 2001).

Daily antioxidants--vitamin C (1,000 mg) and vitamin E (1,000 IU)--given to 45 NASH patients along with a low-fat diet and standard weight-loss counseling in a 6-month randomized, double-blind, placebo-controlled trial significantly improved fibrosis scores without major side effects compared with lifestyle modification alone. But necroinflammatory activity and ALT levels did not improve (Am. J. Gastroenterol. 98[11]:2485-90, 2003).

Agents that have not panned out against NAFLD include ursodiol and tumor necrosis factor [alpha].

Finally, be sure to strongly caution patients against taking unregulated herbal weight-loss remedies--especially the recently banned ephedra--that can lead to liver failure, Dr. Schiff said.

BY MIRIAM E. TUCKER

Senior Writer