NONALCOHOLIC FATTY LIVER DISEASE/ NONALCOHOLIC STEATOHEPATITIS (NASH)/ HEPATIC STEATOSIS/ FATTY LIVER

     Nonalcoholic fatty liver disease (NAFLD) is a form of liver disease that should be considered when either hepatomegaly, transaminasemias or cirrhosis presents without an identifiable etiology after a thorough biochemical work up.  Histologic findings are comparable to those seen in alcoholic hepatitis.  This disorder most commonly afflicts the obese, middle-aged patients, those with diabetes mellitus type II, or the metabolic syndrome.  This is the most common form of cryptogenic cirrhosis.  Nonalcoholic steaohepatitis is an intermediate stage of liver damage on the continuum with simple hepatic steatosis at one end and cirrhosis at the other extreme.  Conditions associated with NASH include obesity, hyperlipidemia, rapid weight loss, starvation, jejunoileal bypass, intestinal resection, drug induced toxicity (amiodarone, perhexilene maleate, glucocorticoids, tamoxifen, methotrexate, synthetic estrogens, and nifedipine), limb lipodystrophy, abetalipoproteinemia, protein malnutrition, extensive small bowel resection, intravenous hyperalimentation, and Weber-Christian disease.

     Most patients manifest only liver enzyme abnormalities; however, some patients with this disorder progress to fibrosis or cirrhosis. The degree of transaminasemia does not correlate with the degree of hepatic damage on biopsy specimens.   Other uncommon laboratory abnormalities include a mild elevation of the alkaline phosphatase level and conjugated hyperbilirubinemia.  Initially, when patients present with hypertransaminasemia all medications which may cause this condition should be discontinued for several months and then repeat testing of the ALT and AST should be performed.  If transaminasemia persists, other conditions including viral hepatitis B and C, drug induced hepatits, and alcoholic liver disease should be excluded before the diagnosis of NAFLD is considered. There is no effective therapy for NASH.  Weight loss may prove effective in obese patients.  Aggressive control of hyperlipidemia and diabetes mellitus may also result in biochemical improvement.  Liver transplantation may be required in those patients who progress to cirrhosis although NASH often develops in the transplanted liver.

     Fatty infiltration of the liver (hepatic steatosis) often manifests as mild hypertransaminasemia.  Ultrasonography, MRI, or computed tomography may be used to demonstrate hepatic fatty infiltration.  Hepatic steatosis is a benign condition.  However, the spectrum of nonalcoholic fatty liver disease (NAFLD) can range from hepatic steatosis to NASH and ultimately cirrhosis.  Treatment at present consists of liver transplantation in appropriate cases when necessary.  It is prudent to recommend aggressive treatment of diabetes mellitus, obesity, and hypertriglyceridemia in patients with these conditions and transaminasemia of unknown cause after an appropriate evaluation.