Non-Alcoholic Fatty Liver Disease Long-term Effects

A new study found that patients with non-alcoholic fatty liver disease (NAFLD) had a significant risk of developing end-stage liver disease and a lower chance of survival if they had non-alcoholic steatohepatitis (NASH), a form of NAFLD that can lead to cirrhosis. The study also found that most NAFLD patients will eventually develop diabetes or impaired glucose tolerance, which can lead to cardiovascular complications.

The results of this study appear in the October 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

Patients with NAFLD, one of the most common causes of liver disease worldwide, often have elevated liver enzymes but no symptoms of the disease. Obesity has been established as a major risk factor for NAFLD and since it is reaching epidemic proportions worldwide, the number of people at risk for developing chronic liver disease is likely to increase in the future. Studies conducted on NAFLD to date have either had small numbers of patients or relatively short follow-up periods. The current study involved the largest reported number of NAFLD patients originally referred because of elevated liver enzymes and followed the patients for more than ten years.

Led by Stergios Kechagias, M.D. of the Division of Internal Medicine at University Hospital in Linkping, Sweden, the study involved 212 patients between 1988 and 1993 who had chronically elevated liver enzymes. All of the patients underwent liver biopsy, and only the 129 patients who had confirmed fatty liver without excessive alcohol consumption or other liver disease participated in the study. A total of 88 patients accepted follow-up at an average of almost 14 years from when they were diagnosed with NAFLD. Of these, 68 patients underwent repeat liver biopsy.

The results showed that NAFLD was found to be associated with a significant risk of developing end-stage liver disease and that death from liver-related causes and cardiovascular diseases was significantly more common in the 71 patients with NASH than in the general population. In addition, 78 percent of NAFLD patients were diagnosed with diabetes or impaired glucose tolerance at follow-up. "Given the strong association between insulin resistance and NAFLD it is reasonable to recommend lifestyle modifications in all patients with NAFLD," the authors state. "Not only do lifestyle modifications reduce the risk of developing type 2 diabetes, intense dietary intervention may also improve liver histology in NAFLD."

In an accompanying editorial in the same issue, Vlad Ratziu and Thierry Poynard of the Universite Pierre et Marie Curie and Assistance Publique-Hopitaux de Paris in Paris, highlight the widespread misconception that NAFLD in its various forms is largely considered to be a mild disease with a good prognosis. They note that NAFLD patients are usually not referred to hepatologists and the only way to accurately diagnose the disease (liver biopsy) is not practical as a screening tool for large populations. Nonetheless, NASH is an important cause of advanced liver disease and it is important to prevent its progression to cirrhosis because once liver failure occurs in these cases the outcome is often fatal. They note that the current study is important not only because of its long follow-up period, but because the authors were able to identify the outcome of different forms of NAFLD. "Remarkably, and possibly because of the longer follow-up, the authors were able to show that even patients without cirrhosis developed ESLD [end-stage liver disease], thus refuting the claim that non-cirrhotic NASH is 'benign.'" They add that the study, along with previously published data, points to the necessity of studying the risk of increased cardiovascular deaths in NASH patients. They conclude that treating NASH is a "major unmet medical need," and that strategies for screening patients with risk factors for liver disease, including obesity, diabetes and heart disease, should be developed.