Fatty liver, also known as fatty liver disease, is a reversible condition wherein large vacuoles
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