of triglyceride fat accumulate in liver cells via the process of steatosis. Despite having

multiple causes, fatty liver can be considered a single disease that occurs worldwide in

those with excessive alcohol intake and the obese. The condition is also associated with

other diseases that influence fat metabolism. It is difficult to distinguish alcoholic FLD

from nonalcoholic FLD, and both show microvesicular and macrovesicular fatty changes at different

stages. Accumulation of fat may also be accompanied

by a progressive inflammation of the liver, called steatohepatitis. By considering the

contribution by alcohol, fatty liver may be termed alcoholic steatosis or nonalcoholic

fatty liver disease, and the more severe forms as alcoholic steatohepatitis and Non-alcoholic

steatohepatitis.

Causes Fatty liver is commonly associated with alcohol

or metabolic syndrome, but can also be due to any one of many causes:

Metabolic Abetalipoproteinemia, glycogen storage diseases,

Weber-Christian disease, acute fatty liver of pregnancy, lipodystrophy

Nutritional Malnutrition, total parenteral nutrition,

severe weight loss, refeeding syndrome, jejunoileal bypass, gastric bypass, jejunal diverticulosis

with bacterial overgrowth Drugs and toxins

Amiodarone, methotrexate, diltiazem, expired tetracycline, highly active antiretroviral

therapy, glucocorticoids, tamoxifen, environmental hepatotoxins

Alcoholic Alcoholism is one of the major cause of fatty

liver due to production of toxic metabolites like aldehydes during metabolism of alcohol

in the liver.This phenomenon most commonly occur with chronic alcoholism.

Other Inflammatory bowel disease, HIV, hepatitis

C, and alpha 1-antitrypsin deficiency Pathology

Fatty change represents the intracytoplasmatic accumulation of triglycerides. At the beginning,

the hepatocytes present small fat vacuoles around the nucleus. In this stage, liver cells

are filled with multiple fat droplets that do not displace the centrally located nucleus.

In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery

of the cell, giving characteristic signet ring appearance. These vesicles are well-delineated

and optically "empty" because fats dissolve during tissue processing. Large vacuoles may

coalesce and produce fatty cysts, which are irreversible lesions. Macrovesicular steatosis

is the most common form and is typically associated with alcohol, diabetes, obesity, and corticosteroids.

Acute fatty liver of pregnancy and Reye's syndrome are examples of severe liver disease

caused by microvesicular fatty change. The diagnosis of steatosis is made when fat in

the liver exceeds 5–10% by weight.

Defects in fatty acid metabolism are responsible for pathogenesis of FLD, which may be due

to imbalance in energy consumption and its combustion, resulting in lipid storage, or

can be a consequence of peripheral resistance to insulin, whereby the transport of fatty

acids from adipose tissue to the liver is increased. Impairment or inhibition of receptor

molecules that control the enzymes responsible for the oxidation and synthesis of fatty acids

appears to contribute to fat accumulation. In addition, alcoholism is known to damage

mitochondria and other cellular structures, further impairing cellular energy mechanism.

On the other hand, nonalcoholic FLD may begin as excess of unmetabolised energy in liver

cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying

cause is reduced or removed.

Severe fatty liver is sometimes accompanied by inflammation, a situation referred to as

steatohepatitis. Progression to alcoholic steatohepatitis or Non-alcoholic steatohepatitis

depends on the persistence or severity of the inciting cause. Pathological lesions in

both conditions are similar. However, the extent of inflammatory response varies widely

and does not always correlate with degree of fat accumulation. Steatosis and onset of

steatohepatitis may represent successive stages in FLD progression.

Liver disease with extensive inflammation and a high degree of steatosis often progresses

to more severe forms of the disease. Hepatocyte ballooning and necrosis of varying degrees

are often present at this stage. Liver cell death and inflammatory responses lead to the

activation of stellate cells, which play a pivotal role in hepatic fibrosis. The extent

of fibrosis varies widely. Perisinusoidal fibrosis is most common, especially in adults,

and predominates in zone 3 around the terminal hepatic veins.

The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis

and by a variety of other sensitizing factors. In alcoholic FLD, the transition to cirrhosis

related to continued alcohol consumption is well-documented, but the process involved

in nonalcoholic FLD is less clear. Diagnosis

Most individuals are asymptomatic and are usually discovered incidentally because of

abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated

liver biochemistry is found in 50% of patients with simple steatosis. The serum alanine transaminase

level usually is greater than the aspartate transaminase level in the nonalcoholic variant

and the opposite in alcoholic FLD. Imaging studies are often obtained during

the evaluation process. Ultrasonography reveals a "bright" liver with increased echogenicity.

Medical imaging can aid in diagnosis of fatty liver; fatty livers have lower density than

spleens on computed tomography, and fat appears bright in T1-weighted magnetic resonance images.

No medical imagery, however, is able to distinguish simple steatosis from advanced NASH. Histological

diagnosis by liver biopsy is sought when assessment of severity is indicated.

Treatment The treatment of fatty liver depends on its

cause, and, in general, treating the underlying cause will reverse the process of steatosis

if implemented at an early stage. Two known causes of fatty liver disease are an excess

consumption of alcohol and a prolonged diet containing foods with a high proportion of

calories coming from lipids. For the patients with non-alcoholic fatty liver disease with

pure steatosis and no evidence of inflammation, a gradual weight loss is often the only recommendation.

In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those

that induce weight loss have been shown to improve liver function.

Complication Up to 10% of cirrhotic alcoholic FLD patients

will develop hepatocellular carcinoma. The overall incidence of liver cancer in nonalcoholic

FLD has not yet been quantified, but the association is well-established.

Epidemiology The prevalence of FLD in the general population

ranges from 10% to 24% in various countries. However, the condition is observed in up to

75% of obese people, 35% of whom progressing to NAFLD, despite no evidence of excessive

alcohol consumption. FLD is the most common cause of abnormal liver function tests in

the United States. "Fatty livers occur in 33% of European-Americans, 45% of Hispanic-Americans,

and 24% of African-Americans." See also

Steatosis Steatohepatitis

Alcoholic liver disease Non-alcoholic fatty liver disease

Metabolic syndrome Cirrhosis

Focal fatty liver References

External links American Association for the Study of Liver

Diseases American Liver Foundation

Fatty Liver Fatty Liver Disease, Canadian Liver Foundation

00474 at CHORUS Photo at Atlas of Pathology