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| __NOTOC__ | | __NOTOC__ |
| '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| | {{Infobox_Disease | |
| | Name = {{PAGENAME}} | |
| | Image = Alcoholic hepatitis 1.jpg | |
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| {{Infobox_Disease |
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| Name = Fatty liver |
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| Image = |
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| Caption = |
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| DiseasesDB = 18844 |
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| ICD10 = {{ICD10|K|70||k|70}}, {{ICD10|K|76|0|k|70}} |
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| ICD9 = {{ICD9|571.0}}, {{ICD9|571.8}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| MeshName = Fatty+Liver |
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| MeshNumber = C06.552.241 |
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| }} | | }} |
| {{Fatty liver}} | | {{Fatty liver}} |
| {{CMG}}; '''Editor-In-Chief:''' Yohanes Buang, PhD [mailto:pajohn_buang@hotmail.com] | | {{CMG}}; {{AE}} Yohanes Buang, PhD [mailto:pajohn_buang@hotmail.com] |
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| {{SK}} steatorrhoeic hepatosis; steatosis hepatitis
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| ==Overview==
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| '''Fatty liver''' (also known as '''steatorrhoeic hepatosis''' or '''steatosis hepatitis''') is the fatty degeneration of the parenchymal cells causing a yellow discoloration of the liver. It is a reversible condition where large [[vacuole]]s of [[triglyceride]] fat accumulate in [[hepatocyte|liver cells]] via the process of [[steatosis]]. Despite having multiple causes, fatty liver disease (FLD) 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 [[metabolism]]<ref name="reddy">{{cite journal |author=Reddy JK, Rao MS |title=Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation |journal=Am. J. Physiol. Fatty liver disease is one of the most deadly dieases ever to be found in someone who has and its very contasious so if someons has if i were u i wouldnt be hanging around with them well thats all from me see u next time. ËĒȲȳǖGastrointest. Liver Physiol. |volume=290 |issue=5 |pages=G852-8 |year=2006 |pmid=16603729 |doi=10.1152/ajpgi.00521.2005}}</ref>. Morphologically it is difficult to distinguish alcoholic FLD from non alcoholic FLD and both show micro-[[Vesicle (biology)|vesicular]] and macrovesicular fatty changes at different stages.
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| ==Causes ==
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| [[Image:Stage of liver damage.JPG|thumb|left|Different stages of liver damage]]
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| 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<ref name="angulo"/><ref name="bayard"/>:
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| ;Metabolic: [[Abetalipoproteinemia]], [[glycogen storage disease]]s, [[Weber-Christian disease]], [[Wolman disease|Wolmans disease]], [[acute fatty liver of pregnancy]], [[lipodystrophy]]
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| ;Nutritional:[[Malnutrition]], [[total parenteral nutrition]], severe [[weight loss]], [[refeeding syndrome]], [[jejuno-ileal bypass]], [[Gastric bypass surgery|gastric bypass]], jejunal [[diverticulosis]] with [[Small bowel bacterial overgrowth syndrome|bacterial overgrowth]]
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| ;Drugs and toxins:[[Amiodarone]], [[methotrexate]], [[diltiazem]], [[highly active antiretroviral therapy]], [[glucocorticoids]], [[tamoxifen]], environmental [[hepatotoxin]]s (e.g. [[phosphorus]], toxic [[mushroom]])
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| ;Other:[[Inflammatory bowel disease]], [[HIV]]
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| ==Pathology==
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| Fatty change represents the intra-[[cytoplasm]]ic accumulation of triglyceride (neutral fats). At the beginning, the hepatocytes present small fat vacuoles ([[liposomes]]) around the [[Cell nucleus|nucleus]] - '''microvesicular [[Steatosis|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 [[cyst]]s - 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<ref>{{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 }}</ref>. The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight<ref>{{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=}}</ref><ref>{{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}}</ref><ref name="reddy"/>.
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| [[Image:Steatosis.jpg|thumb|left|Mechanism leading to hepatic steatosis]]
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| Defects in [[Fatty acid metabolism|fat metabolism]] is 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<ref>{{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=}}</ref><ref name="reddy"/>.
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| Impairment or inhibition of receptor molecules ([[Peroxisome proliferator-activated receptor|PPAR-α]], [[Peroxisome proliferator-activated receptor|PPAR-γ]] and [[sterol regulatory element binding protein|SREBP1]]) that control the enzymes responsible for the oxidation and synthesis of fatty
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| acids 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.
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| Severe fatty liver is accompanied by [[inflammation]], a situation that is referred to as ''[[steatohepatitis]]''. Progression to alcoholic [[steatohepatitis]] (ASH) or [[Non-alcoholic fatty liver disease|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 progression<ref name="pmid9547102">{{cite 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=}}</ref>.
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| Liver with extensive inflammation and high degree of steatosis often progresses to more severe forms of the disease<ref>{{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=}}</ref>. [[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 [[Ito cell|stellate cells]] which play a pivotal role in hepatic [[fibrosis]]. The extent of fibrosis varies widely. Peri[[Sinusoid (blood vessel)|sinusoidal]] fibrosis is most common, especially in adults, and predominates in [[Hepatic lobule|zone 3]] around the terminal [[hepatic veins]]<ref>{{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}}</ref>.
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| 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.
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| == Diagnosis==
| | {{SK}} Steatorrhoeic hepatosis; steatosis hepatitis; hepatic steatosis; FLD |
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| 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<ref>{{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 }}</ref>. The serum [[Alanine transaminase|ALT]] level usually is greater than the [[AST]] level in non-alcoholic variant and the opposite in alcoholic FLD.
| | {{See also|Non-alcoholic fatty liver disease}} |
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| Imaging studies are often obtained during evaluation process. [[Ultrasonography]] reveals a "bright" liver with increased [[echogenicity]]. A fatty liver has lower [[density]] than [[spleen]] on [[CT scan]] and fat appears bright in T1 weighted [[MRI]]. No radiological modality is however able to distinguish simple steatosis from advanced [[Non-alcoholic fatty liver disease|NASH]]. [[Histological]] diagnosis by [[liver biopsy]] is sought when assessment of severity is indicated.
| | ==[[Fatty liver overview|Overview]]== |
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| === CT === | | ==[[Fatty liver historical perspective|Historical Perspective]]== |
| Findings are
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| * A decrease in mean hepatic attenuation values proportional to the degree of increase of the hepatic triglycerids.
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| * Intrahepatic vessels are more clearly distinguished as hyperattenuating structures from the surrounding liver parenchyma
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| * In normal individuals the attenuation value of the liver is slightly higher than that of the spleen. In fatty liver infiltration the attenuation values of both organs tend to be equal or the ratios may be reversed.
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| * Does not cause any mass effect nor contour deformation of the organ.
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| * Intrahepatic vessels follow their normal course through the lesion without deformity.
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| '''Patient #1'''
| | ==[[Fatty liver classification|Classification]]== |
| <gallery>
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| Image:
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| Hepatic-fatty-infiltration-001.jpg|No contrast
| | ==[[Fatty liver pathophysiology|Pathophysiology]]== |
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| Image:
| | ==[[Fatty liver causes|Causes]]== |
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| Hepatic-fatty-infiltration-002.jpg|No contrast
| | ==[[Fatty liver differential diagnosis|Differentiating Fatty Liver from other Diseases]]== |
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| Image:
| | ==[[Fatty liver epidemiology and demographics|Epidemiology and Demographics]]== |
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| Hepatic-fatty-infiltration-003.jpg|Contrast enhanced
| | ==[[Fatty liver risk factors|Risk Factors]]== |
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| | ==[[Fatty liver screening|Screening]]== |
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| Hepatic-fatty-infiltration-004.jpg|Contrast enhanced
| | ==[[Fatty liver natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| </gallery>
| | ==Diagnosis== |
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| '''Patient #2: Perivascular fatty infiltration'''
| | [[Fatty liver history and symptoms|History and Symptoms]] | [[Fatty liver physical examination|Physical Examination]] | [[Fatty liver laboratory findings|Laboratory Findings]] | [[Fatty liver electrocardiogram|Electrocardiogram]] | [[Fatty liver x ray|X Ray]] | [[Fatty liver CT|CT]] | [[Fatty liver MRI|MRI]] | [[Fatty liver ultrasound|Ultrasound]] | [[Fatty liver other imaging findings|Other Imaging Findings]] | [[Fatty liver other diagnostic studies|Other Diagnostic Studies]] |
| <gallery>
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| Image:
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| Perivascular fatty infiltration 001.jpg
| | ==Treatment== |
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| Image:
| | [[Fatty liver medical therapy|Medical Therapy]] | [[Fatty liver surgery|Surgery]] | [[Fatty liver primary prevention|Primary Prevention]] | [[Fatty liver secondary prevention|Secondary Prevention]] | [[Fatty liver cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Fatty liver future or investigational therapies|Future or Investigational Therapies]] |
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| Perivascular fatty infiltration 002.jpg
| | ==Case Studies== |
| | [[Fatty liver case study one|Case #1]] |
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| | ==Related Chapters== |
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| Perivascular fatty infiltration 003.jpg
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| Image:
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| Perivascular fatty infiltration 004.jpg
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| </gallery>
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| '''Patient #3: Fatty infiltration on ultrasound'''
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| <gallery>
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| Image:
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| Fatty infiltration of liver ultrasound 001.jpg
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| Fatty infiltration of liver ultrasound 002.jpg
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| </gallery>
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| '''Patient #4: Fatty liver on ultrasound. Note that liver is very echogenic when compared to right kidney'''
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| <gallery>
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| Fatty infiltration of liver ultrasound 101.jpg
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| Fatty infiltration of liver ultrasound 102.jpg
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| Fatty infiltration of liver ultrasound 103.jpg
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| </gallery>
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| == Differential Diagnosis == | |
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| {|align="right"
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| |-
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| !align="center"|Flow chart for diagnosis, modified from<ref name="bayard">{{cite journal |author=Bayard M, Holt J, Boroughs E |title=Nonalcoholic fatty liver disease |journal=American family physician |volume=73 |issue=11 |pages=1961-8 |year=2006 |pmid=16770927 |doi=}}</ref>
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| |{{familytree/start}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | A01| | | |A01=Elevated liver enzyme}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | |!| | | | |}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | B01| | | |B01=Serology to exclude viral hepatitis}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | |!| | | | |}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | C01| | | |C01=Imaging study showing<br />fatty infiltrate}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | |!| | | | |}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | | | D01| | | |D01=Assess alcohol intake}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | |,|-|^|-|.| | |}}
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| {{familytree |border=1|boxstyle=background:#dfd; | |E01| |E02| | |E01=Less than 2 drinks per day‡|E02=More than 2 drinks per day‡}}
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| {{familytree |border=1|boxstyle=background:#dfd; | | |!| | | |!| | |}}
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| {{familytree |border=1|boxstyle=background:#dfd; | |F01| |F02| | |F01=Non alcoholic fatty liver disease likely|F02=Alcoholic fatty liver disease likely}}
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| {{familytree/end}}
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| |-
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| |‡ <small>''Criteria for nonalcoholic fatty liver disease:<br /> consumption of ethanol less than 20g/day for woman and 30g/day for man<ref>{{cite journal |author=Adams LA, Angulo P, Lindor KD |title=Nonalcoholic fatty liver disease |journal=CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne |volume=172 |issue=7 |pages=899-905 |year=2005 |pmid=15795412 |doi=10.1503/cmaj.045232}}</ref>''</small>
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| |}
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| * [[Abetalipoproteinemia]]
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| * Aryl-dehydrogenase deficiency
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| * [[Cystic Fibrosis]]
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| * [[Diabetes Mellitus]]
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| * Disorders of lipid metabolism
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| * Drugs, toxins
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| * Fructose intolerance
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| * Galactose metabolism
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| * Glycogen metabolism
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| * Homocystine metabolism
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| * [[Inflammatory Bowel Disease]]
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| * Intestinal bypass surgery
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| * [[Obesity]]
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| * Parenteral nutrition
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| * [[Pregnancy]]
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| * Protein malnutrition, deficiency
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| * Refsum's Disease
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| * [[Reye's Syndrome]]
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| * Starvation, rapid weight loss
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| * Tyrosine metabolism
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| * [[Weber-Christian Disease]]
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| * [[Wilson's Disease]]<ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:142 isbn=1591032016</ref>
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| ==Treatment and prevention==
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| 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.
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| == Complication ==
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| Up to 10% of cirrhotic alcoholic FLD will develop [[hepatocellular carcinoma]]. Overall incidence of liver cancer in non-alcoholic FLD has not been assessed yet but the association is well established<ref>{{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=}}</ref>.
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| == Epidemiology==
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| FLD is prevalent among 10%- 24% of general population in various countries<ref name="angulo"/>. However among obese individuals the condition is observed in up to 75% of people, 35% of whom, despite no evidence of excessive alcohol consumption, will lead to [[Non-alcoholic fatty liver disease|non alcoholic FLD]]<ref>{{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=}}</ref>. It is the commonest cause of abnormal [[liver function test]] in the US<ref name="angulo">{{cite 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}}</ref>. African Americans and Mexican Americans have higher frequencies of unexplained serum [[Transaminase|aminotransferase]] elevations than those reported in whites but prevalence of FLD among different racial groups is not known.
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| == See also==
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| *[[Steatosis]] | | *[[Steatosis]] |
| *[[Steatohepatitis]]
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| *[[Non-alcoholic fatty liver disease]] | | *[[Non-alcoholic fatty liver disease]] |
| *[[Metabolic syndrome]] | | *[[Metabolic syndrome]] |
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| *[[Cirrhosis]] | | *[[Cirrhosis]] |
| *[[Focal fatty liver]] | | *[[Focal fatty liver]] |
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| == Reference==
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| {{Reflist|2}}
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| ==External links==
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| * [http://www.aasld.org American Association for the Study of Liver Disease]
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| * [http://www.liverfoundation.org '''American Liver Foundation''']
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| * {{MerckManual|4|39|a}}
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| * Photo at: [http://www.pathologyatlas.ro/Liver%20Steatosis.html Atlas of Pathology]
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| * {{Chorus|00474}}
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| {{Gastroenterology}} | | {{Gastroenterology}} |
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| [[Category:Hepatology]] | | [[Category:Hepatology]] |
| [[Category:Medical conditions related to obesity]]
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| [[Category:Histopathology]]
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| [[Category:Gastroenterology]] | | [[Category:Gastroenterology]] |
| | [[Category:Disease]] |
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| [[de:Fettleber]] | | [[de:Fettleber]] |
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