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Hepatology

Researchers to study the effects of lifestyle changes on nonalcoholic fatty liver disease

09/01/2006

Nonalcoholic Fatty Liver Disease (NAFLD) comprises a spectrum of liver disorders that range from simple fat accumulation in the liver to fat accumulation accompanied by inflammation – nonalcoholic steatohepatitis or NASH – through cirrhosis of the liver and liver cancer. NAFLD is strongly linked with obesity. Autopsy studies have shown that steatosis – or fat in the liver – is seen in up to 70 percent those who are obese and in up to 35 percent of non-obese people. The presence of fat in the liver and liver damage are more closely related to abdominal fat than to body mass index; waist to hip ratio is the best predictor of NAFLD. NAFLD usually manifests during the fourth through sixth decades of life and affects men and women equally.

NAFLD and the metabolic syndrome

NAFLD is a component of the metabolic syndrome along with (1) insulin resistance or diabetes, (2) hyperlipidemia, (3) hypertension, and (4) truncal obesity. The mechanism involved appears to be an abnormal suppression of lipolysis by insulin. This results in increased fatty acids in the blood and liver, decreased metabolic clearance of glucose by the muscles, and increased glucose concentration in the blood. This leads to greater insulin production by the pancreas. Insulin resistance with hyperinsulinemia is common to almost all patients with fatty liver disease.

Because fatty liver progresses to cirrhosis and liver cancer in some patients and not in others, it appears that there is another component to the process. Many experts believe it to be increased radical oxygen species, or an imbalance in the equilibrium of oxidants and antioxidants, leading to inflammation.

Diagnosis and care

Diagnosing NAFLD is a matter of demonstrating the presence of fatty infiltration of the liver and ruling out other causes, such as excessive alcohol consumption. Patients typically present either with abnomal liver tests found incidentally or fatty liver seen on imaging studies, such as ultrasound or computed tomography (CT) scan. The diagnosis can be confirmed with a liver biopsy, which can provide histological staging to help establish a prognosis, though some experts argue against liver biopsy as an unnecessary procedure given the limited therapeutic options.

A number of approaches to treating NAFLD are being studied, but most have yet to provide conclusive results. Among overweight patients, it would seem logical that weight loss would improve NAFLD. While some studies have shown that weight reduction produces improvements in liver tests and in fat seen on ultrasound, other studies have shown little benefit from weight reduction, and because follow-up biopsy data has not been available, the effect of weight reduction remains in question.

Similarly, studies of lipid-lowering agents have failed to establish a clear-cut benefit despite the fact that nearly all NAFLD patients have hyperlipidemia. Antioxidants have produced some positive results, but there have not yet been the type of large, well-designed studies needed to establish the usefulness of antioxidant therapy.

Diabetes medications have produced decreases in insulin resistance and promising liver test and histological results in early studies, and there is currently a large, multi-center trial of pioglitazone and vitamin E being conducted that may shed more light on these therapies.

At UCLA, physicians treat NAFLD using a multidisciplinary approach. They treat the metabolic syndrome as aggressively as possible while also treating the hypertension, hyperlipidemia, and obesity. The weight loss program at UCLA employs a low-fat diet and regular exercise to help patients lose weight slowly. The initial target is to lose 10
percent of the weight over six months using monthly milestones.

A new study is currently getting underway at UCLA to examine the effects of lifestyle modification on NAFLD. Working with the Department of Nutrition, UCLA hepatologists will enroll patients in a program using a lowfat, high-antioxidant diet and exercise. Patients will be monitored for weight loss and metabolic changes – such as decreased insulin resistance – and will undergo liver biopsy at the conclusion of the study to measure histological results.

Patient referral

Patients suspected of having fatty liver disease should be referred as soon as possible. Physicians evaluate them for cirrhosis and liver cancer and can begin treating them early. For more information or to schedule an appointment, call:

(310) 206-6705 Program administrator
(310) 794-7788 Clinic administrator

Participating physician

Francisco Durazo, M.D.





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