Fatty liver

, ICD9|571.8
ICDO =
OMIM =
MedlinePlus =
eMedicineSubj = med
eMedicineTopic = 775
MeshName = Fatty+Liver
MeshNumber = C06.552.241

Fatty liver, also known as fatty liver disease (FLD), steatorrhoeic hepatosis, or steatosis hepatitis, is a reversible condition where 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 those who are obese (with or without effects of insulin resistance). The condition is also associated with other diseases that influence fat metabolismcite journal |author=Reddy JK, Rao MS |title=Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation |journal=Am. J. Physiol. Gastrointest. Liver Physiol. |volume=290 |issue=5 |pages=G852–8 |year=2006 |pmid=16603729 |doi=10.1152/ajpgi.00521.2005] . Morphologically it is difficult to distinguish alcoholic FLD from non alcoholic FLD and both show micro-vesicular and macrovesicular fatty changes at different stages.

Causes

Fatty liver is commonly associated with alcohol or metabolic syndrome (diabetes, hypertension and dyslipidemia) but can also be due to any one of many causes:;Metabolic: Abetalipoproteinemia, glycogen storage diseases, Weber-Christian disease, Wolman disease, acute fatty liver of pregnancy, lipodystrophy;Nutritional:Malnutrition, total parenteral nutrition, severe weight loss, refeeding syndrome, jejuno-ileal bypass, gastric bypass, jejunal diverticulosis with bacterial overgrowth;Drugs and toxins:Amiodarone, methotrexate, diltiazem, highly active antiretroviral therapy, glucocorticoids, tamoxifen, environmental hepatotoxins (e.g. phosphorus, toxic mushroom);Other:Inflammatory bowel disease, HIV

Pathology

Fatty change represents the intra-cytoplasmic accumulation of triglyceride (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus - microvesicular fatty change. In this stage liver cells are filled with multiple fat droplets that do not displace 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 - macrovesicular fatty change. These vesicles are well delineated and optically "empty" because fats dissolve during tissue processing. Large vacuoles may coalesce, producing fatty cysts - which are irreversible lesions. [http://www.pathologyatlas.ro/Liver%20Steatosis.html] . 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 [cite book | last = Goldman | first = Lee | title = Cecil Textbook of Medicine -- 2-Volume Set, Text with Continually Updated Online Reference | publisher = W.B. Saunders Company | location = Philadelphia | year = 2003 | isbn = 0721645631 ] . The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight [cite journal |author=Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P |title=The natural history of nonalcoholic fatty liver disease: a population-based cohort study |journal=Gastroenterology |volume=129 |issue=1 |pages=113–21 |year=2005 |pmid=16012941 |doi=10.1053/j.gastro.2005.04.014] [cite journal |author=Crabb DW, Galli A, Fischer M, You M |title=Molecular mechanisms of alcoholic fatty liver: role of peroxisome proliferator-activated receptor alpha |journal=Alcohol |volume=34 |issue=1 |pages=35–8 |year=2004 |pmid=15670663 |doi=10.1016/j.alcohol.2004.07.005] .

Defects in fat 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 [cite journal |author=Medina J, Fernández-Salazar LI, García-Buey L, Moreno-Otero R |title=Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis |journal=Diabetes Care |volume=27 |issue=8 |pages=2057–66 |year=2004 |pmid=15277442 |doi=10.2337/diacare.27.8.2057] .Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fattyacids appears to contribute towards fat accumulation. In addition alcoholism is known to damage mitochondria and other cellular structure further impairing cellular energy mechanism. On the other hand non alcoholic FLD may begin as excess of unmetabolised energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if there is cessation or removal of underlying cause.

Severe fatty liver is sometimes accompanied by inflammation, a situation that is referred to as "steatohepatitis". Progression to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH) depend on persistence or severity of 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 (retention of lipid) and onset of steatohepatitis may represent successive stages in FLD progressioncite journal |author=Day CP, James OF |title=Steatohepatitis: a tale of two "hits"? |journal=Gastroenterology |volume=114 |issue=4 |pages=842–5 |year=1998 |pmid=9547102 |doi=10.1016/S0016-5085(98)70599-2] .

Liver with extensive inflammation and high degree of steatosis often progresses to more severe forms of the disease [cite journal |author=Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA, Boparai N, Younossi ZM |title=Pathologic features associated with fibrosis in nonalcoholic fatty liver disease |journal=Hum. Pathol. |volume=35 |issue=2 |pages=196–9 |year=2004 |pmid=14991537 |doi=10.1016/j.humpath.2003.09.018] . Hepatocyte ballooning and hepatocyte necrosis of varying degree 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 [cite journal |author=Zafrani ES |title=Non-alcoholic fatty liver disease: an emerging pathological spectrum |journal=Virchows Arch. |volume=444 |issue=1 |pages=3–12 |year=2004 |pmid=14685853 |doi=10.1007/s00428-003-0943-7] .

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 non-alcoholic 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 condition. Elevated liver biochemistry is found in 50% of patients with simple steatosis [cite book | last = Sleisenger | first = Marvin | title = Sleisenger and Fordtran's Gastrointestinal and Liver Disease | publisher = W.B. Saunders Company | location = Philadelphia | year = 2006 | isbn = 1416002456 ] . The serum ALT level usually is greater than the AST level in non-alcoholic variant and the opposite in alcoholic FLD.

Imaging studies are often obtained during 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 spleen on computed tomography (CT) and fat appears bright in T1-weighted magnetic resonance images (MRIs). 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 and prevention

The treatment of fatty liver depends on what is causing it, and generally, treating the underlying cause will reverse the process of steatosis if implemented at early stage.

Complication

Up to 10% of cirrhotic alcoholic FLD will develop hepatocellular carcinoma. Overall incidence of liver cancer in non-alcoholic FLD has not yet been quantified, but the association is well established [cite journal |author=Qian Y, Fan JG |title=Obesity, fatty liver and liver cancer |journal=HBPD INT |volume=4 |issue=2 |pages=173–7 |year=2005 |pmid=15908310 |doi=] .

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 will progress to non-alcoholic FLD [cite journal |author=Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, Omatsu T, Nakajima T, Sarui H, Shimazaki M, Kato T, Okuda J, Ida K |title=The metabolic syndrome as a predictor of nonalcoholic fatty liver disease |journal=Ann. Intern. Med. |volume=143 |issue=10 |pages=722–8 |year=2005 |pmid=16287793 |doi=] , despite no evidence of excessive alcohol consumption. FLD is the most common cause of abnormal liver function test in the UScite journal |author=Angulo P |title=Nonalcoholic fatty liver disease |journal=N. Engl. J. Med. |volume=346 |issue=16 |pages=1221–31 |year=2002 |pmid=11961152 |doi=10.1056/NEJMra011775] . Hispanic-Americans and European-Americans have higher frequencies of unexplained serum aminotransferase elevations than those reported in African-Americans (http://www.webmd.com/digestive-disorders/news/20080925/fatty-liver-disease-genes-affect-risk), but prevalence of FLD among different racial groups is not known.

See also

*Steatosis
*Steatohepatitis
*Non-alcoholic fatty liver disease
*Metabolic syndrome
*Alcoholic liver disease
*Cirrhosis
*Focal fatty liver

References

External links

* [http://www.aasld.org American Association for the Study of Liver Disease]
* [http://www.liverfoundation.org American Liver Foundation]
* Photo at: [http://www.pathologyatlas.ro/Liver%20Steatosis.html Atlas of Pathology]
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