(Hepatic Steatosis)

Fatty liver 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 fatty liver due to pregnancy or alcoholic liver disease (see Alcoholic Liver Disease) from that occurring in the absence of pregnancy and alcoholism (nonalcoholic fatty liver disease [NAFLD]). NAFLD 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 on nonalcoholic fatty liver disease.)

Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is a syndrome that develops in patients who are not alcoholic; it causes liver damage that is histologically indistinguishable from alcoholic hepatitis. It develops most often in patients with at least one of the following risk factors: obesity, dyslipidemia, and glucose intolerance. Pathogenesis is poorly understood but seems to be linked to insulin resistance (eg, as in obesity or 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.

NASH (sometimes called steatonecrosis) is diagnosed most often in patients between 40 yr and 60 yr but can occur in all age groups. Many affected patients have obesity, type 2 diabetes mellitus, or dyslipidemia.

Pathophysiology

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.

Symptoms and Signs

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 can be asymptomatic and may lack the usual signs of chronic liver disease.

Diagnosis

• History (presence of risk factors, absence of excessive alcohol intake)
• Serologic tests that rule out hepatitis B and C
• Liver biopsy

The diagnosis should be suspected in patients with risk factors such as obesity, type 2 diabetes mellitus, or dyslipidemia and in patients with unexplained laboratory abnormalities suggesting liver disease. The most common laboratory abnormalities are elevations in aminotransferase levels. Unlike in 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) that alcohol intake is not excessive (eg, is < 20 g/day) is needed, and serologic tests should show absence of hepatitis B and C (ie, hepatitis B surface antigen and hepatitis C virus antibody should be negative). Liver biopsy reveals 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 (eg, splenomegaly, cytopenia) and unexplained elevations in aminotransferase levels that persist for > 6 mo in a patient with diabetes, obesity, or dyslipidemia.

Imaging tests, including ultrasonography, 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

Prognosis is hard to predict. 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.

Treatment

• Elimination of causes and control of risk factors

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 dyslipidemia or hyperglycemia. Preliminary evidence suggests that thiazolidinediones and vitamin E can help correct biochemical and histologic abnormalities in NASH. Many other treatments (eg, ursodeoxycholic acid, metronidazoleSome Trade Names
FLAGYL
Click for Drug Monograph
, metforminSome Trade Names
GLUCOPHAGE
Click for Drug Monograph
, betaineSome Trade Names
CYSTADANE
Click for Drug Monograph
, glucagon, glutamine infusion) have not been proved effective.

Key Points

• NASH causes histologic liver damage similar to that in alcoholic hepatitis but occurs in patients who are not alcoholics and who often are obese or have type 2 diabetes mellitus or dyslipidemia.
• Symptoms are usually absent, but some patients have right upper quadrant discomfort, fatigue, and/or malaise.
• Signs of portal hypertension and cirrhosis can eventually occur and may be the first manifestations.
• Rule out alcoholism (based on corroborated history) and hepatitis B and C (with serologic tests) and do a liver biopsy.
• Eliminate causes and control risk factors when possible.

Last full review/revision September 2012 by Steven K. Herrine, MD

Content last modified November 2012