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Fatty liver
(hepatic steatosis) is excessive accumulation of lipid in hepatocytes,
the most common liver response to injury.
Fatty liver develops for many reasons, involves many different biochemical mechanisms, and causes different types of liver damage. Clinically, it is most useful to distinguish between fatty liver due to pregnancy, that due to alcoholic liver disease (see Alcoholic Liver Disease), and that developing in the absence of pregnancy and alcoholism (nonalcoholic fatty liver disease [NAFLD]). The latter includes simple fatty infiltration (a benign condition) and nonalcoholic steatohepatitis, a less common but more important variant. (See also the American Gastroenterological Association's Medical
Position Statement and Technical
Review on nonalcoholic fatty liver disease.)
Nonalcoholic
Steatohepatitis (NASH)
Nonalcoholic
steatohepatitis is a syndrome that develops in patients who are
not alcoholic and produces liver damage that is histologically indistinguishable
from alcoholic hepatitis. It develops most often in middle-aged
women, many of whom are overweight or have increased blood sugar
or lipids. Pathogenesis is poorly understood but appears to be linked
to insulin resistance (eg, as in obesity or the metabolic syndrome).
Most patients are asymptomatic. Laboratory findings include elevations
in aminotransferase levels. Biopsy is required to confirm the
diagnosis. Treatment includes elimination of causes and risk factors.
Nonalcoholic steatohepatitis (NASH—sometimes called steatonecrosis) is diagnosed most often in women between 40 and 60, many of whom have obesity, type 2 diabetes mellitus, or hyperlipidemia, but can occur in all ages and both sexes.
Pathophysiology involves fat accumulation (steatosis), inflammation, and, variably, fibrosis. Steatosis results from hepatic triglyceride accumulation. Possible mechanisms for steatosis include reduced synthesis of very low density lipoprotein (VLDL) and increased hepatic triglyceride synthesis (possibly due to decreased oxidation of fatty acids or increased free fatty acids being delivered to the liver). Inflammation may result from lipid peroxidative damage to cell membranes. These changes can stimulate hepatic stellate cells, resulting in fibrosis. If advanced, NASH can cause cirrhosis and portal hypertension.
Most patients are asymptomatic. However, some have fatigue, malaise, or right upper quadrant abdominal discomfort. Hepatomegaly develops in about 75% of patients. Splenomegaly may develop if advanced hepatic fibrosis is present and is usually the first indication that portal hypertension has developed. Patients with cirrhosis due to NASH are often asymptomatic and may lack the usual signs of chronic liver disease.
Diagnosis
The most common laboratory abnormalities are elevations in aminotransferase levels. Unlike alcoholic liver disease, the ratio of AST/ALT in NASH is usually < 1. Alkaline phosphatase and γ‑glutamyl transpeptidase (GGT) occasionally increase. Hyperbilirubinemia, prolongation of PT, and hypoalbuminemia are uncommon.
For diagnosis, strong evidence (such as a history corroborated by friends and relatives) should confirm that alcohol intake is not excessive (eg, < 20 g/day). Serology should demonstrate absence of hepatitis B and C infection (ie, hepatitis B surface antigen and hepatitis C virus antibody should be negative). Liver biopsy should reveal damage similar to that seen in alcoholic hepatitis, usually including large fat droplets (macrovesicular fatty infiltration). Indications for biopsy include unexplained signs of portal hypertension (including splenomegaly or cytopenia) and unexplained elevations in aminotransferase levels that persist for > 6 mo in a patient with diabetes, obesity, or hyperlipidemia. Imaging tests, including ultrasound, CT, and, particularly, MRI, may identify hepatic steatosis. However, these tests cannot identify the inflammation typical of NASH and cannot differentiate NASH from other causes of hepatic steatosis.
Prognosis
and Treatment
Prognosis is controversial. Probably, most patients do not develop hepatic insufficiency or cirrhosis. However, some drugs (eg, cytotoxic drugs) and metabolic disorders are associated with acceleration of NASH. Prognosis is often good unless complications (eg, variceal hemorrhage) develop.
The only widely accepted treatment goal is to eliminate potential causes and risk factors. Such a goal may include discontinuation of drugs or toxins, weight loss, and treatment for hyperlipidemia or hyperglycemia. Many other treatments (eg, ursodeoxycholic acid, vitamin E, metronidazole , metformin , betaine , glucagon, glutamine infusion) have not been proven effective.
Last full review/revision November 2005
Content last modified November 2005
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