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__NOTOC__
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Elliot Tapper, M.D.
{{Non alcoholic fatty liver disease}}
{{CMG}}; {{AE}} {{VKG}}


{{Editor Help}}
{{See also|Fatty liver}}


==Overview==
'''For the patient information page on this topic, click [[non-alcoholic fatty liver disease (patient information)|here]].'''
{{DiseaseDisorder infobox |
  Name        = Non-alcoholic steatohepatitis |
  Image          = |
  Caption        = |
  DiseasesDB    = 29786|
  ICD10          = {{ICD10|K|76|0|k|70}} |
  ICD9          = {{ICD9|571.8}} |
  ICDO          = |
  OMIM          = |
  MedlinePlus    = |
  eMedicineSubj  = med |
  eMedicineTopic = 775 |
}}
{{SI}}
'''Non-alcoholic fatty liver disease''' ('''[[NAFLD]]''') is fatty [[inflammation]] of the [[liver]] when this is not due to excessive [[alcoholism|alcohol]] use. It is related to [[insulin resistance]] and the [[metabolic syndrome]], and may respond to treatments originally developed for other insulin resistant states (e.g. [[diabetes mellitus type 2]]), such as weight loss, [[metformin]] and [[thiazolidinedione]]s.<ref name=Adams>Adams LA, Angulo P. Treatment of non-alcoholic fatty liver disease. ''Postgrad Med J'' 2006;82:315-22. PMID 16679470.</ref> '''[[Non-alcoholic steatohepatitis]]''' ([[NASH]]) is the most extreme form of NAFLD, which is regarded as a major cause of cryptogenic [[cirrhosis]] of the liver.<ref name=Clark>Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. ''JAMA'' 2003;289:3000-4. PMID 12799409.</ref>


==Signs and symptoms==
{{SK}} NASH, NAFLD, non-alcoholic steatohepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD)
===Symptoms and associations===
Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, [[malaise]] and dull right upper quadrant [[abdominal pain|abdominal discomfort]]. Mild [[jaundice]] can rarely be noticed. More commonly it is diagnosed as a result of abnormal [[liver function tests]] during routine blood tests. By definition, alcohol consumption of over 20 g/day excludes the condition.<ref name=Adams/>


NAFLD is associated with [[insulin resistance]] and the [[metabolic syndrome]] ([[obesity]], [[combined hyperlipidemia]], [[Diabetes mellitus type 2|diabetes mellitus (type II)]] and [[hypertension|high blood pressure]]).<ref name=Clark/><ref name=Adams/>
==[[Non-alcoholic fatty liver disease overview|Overview]]==


===Secondary causes===
==[[Non-alcoholic fatty liver disease historical perspective|Historical Perspective]]==
NAFLD can also be caused by the following medications (termed ''secondary'' NAFLD):
* [[Amiodarone]]
* [[Antiviral drug]]s ([[nucleoside analogues]])
* [[Aspirin]] / [[NSAID]]S
* [[Corticosteroid]]s
* [[Methotrexate]]
* [[Nifedipine]]
* [[Perhexiline]]
* [[Tamoxifen]]
* [[Tetracycline]]
* [[Valproic acid]]


==Diagnosis==
==[[Non-alcoholic fatty liver disease classification|Classification]]==
Disturbed [[liver enzyme]]s are common, and liver [[medical ultrasonography|ultrasound]] may show [[steatosis]]; it may also be used to exclude [[gallstone]] problems ([[cholelithiasis]]). A [[biopsy]] (tissue examination) of the [[liver]] is the only widely accepted test which can distinguish NASH from other forms of liver disease, and can be used to assess the severity of the inflammation and resultant fibrosis.<ref name=Adams/>
 
==[[Non-alcoholic fatty liver disease pathophysiology|Pathophysiology]]==
 
==[[Non-alcoholic fatty liver disease causes|Causes]]==
 
==[[Non-alcoholic fatty liver disease differential diagnosis|Differentiating Non-Alcoholic Fatty Liver Disease from other Diseases]]==
 
==[[Non-alcoholic fatty liver disease epidemiology and demographics|Epidemiology and Demographics]]==
 
==[[Non-alcoholic fatty liver disease risk factors|Risk Factors]]==


Other tests generally performed are other blood tests ([[erythrocyte sedimentation rate]], [[glucose]], [[human serum albumin|albumin]], [[renal function]] etc.) As the liver is important in [[coagulation]], some coagulation studies will generally be done, especially the INR (international normalized ratio). To distinguish this disease from viral [[hepatitis]], blood tests ([[serology]]) are generally done (hepatitis A, B, C, [[Epstein-Barr virus|EBV]], [[CMV]] and [[herpes]] viruses, as well as [[rubella]]) to ensure these are not playing a role. Additionally, autoimmune causes are ruled out with serology. [[Thyroid-stimulating hormone|TSH]] is warranted, as [[hypothyroidism]] is more prevalent in NASH patients.<ref>Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? ''J Clin Gastroenterol'' 2003;37:340-3. PMID 14506393</ref>
==[[Non-alcoholic fatty liver disease screening|Screening]]==


==Pathophysiology==
==[[Non-alcoholic fatty liver disease natural history, complications and prognosis|Natural History, Complications, and Prognosis]]==
NAFLD is considered a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic [[steatosis]]). A fatty liver can remain without disturbing the function of the liver, but by varying mechanisms and possible insults to the liver, may progress to outright [[inflammation]] of the liver.  When inflammation occurs in this setting, the condition is then called NASH. Over time, up to 20 percent of patients with NASH may develop [[cirrhosis]].


The exact cause is still ''unknown''. However both [[obesity]] and [[insulin resistance]] likely play a strong role in this disease process. The exact reasons and mechanisms by which this disease progresses from one entity to the next is a subject of much research and debate.
==Diagnosis==
One such debated mechanisim proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to  [[hepatic]] inflammation. [[Oxidative stress]], hormonal imbalances and [[Mitochondrion|mitochondrial]] abnormalities may be potential causes for this  "second hit" phenomenon.<ref name=Adams/>
[[Non-alcoholic fatty liver disease history and symptoms|History and Symptoms]] | [[Non-alcoholic fatty liver disease physical examination|Physical Examination]] | [[Non-alcoholic fatty liver disease laboratory findings|Laboratory Findings]] | [[Non-alcoholic fatty liver disease electrocardiogram|Electrocardiogram]] | [[Non-alcoholic fatty liver disease x ray|X Ray]] | [[Non-alcoholic fatty liver disease CT|CT]] | [[Non-alcoholic fatty liver disease MRI|MRI]] | [[Non-alcoholic fatty liver disease ultrasound|Ultrasound]] | [[Non-alcoholic fatty liver disease other imaging findings|Other Imaging Findings]] | [[Non-alcoholic fatty liver disease other diagnostic studies|Other Diagnostic Studies]] | [[Non-alcoholic fatty liver disease Noninvasive scores| Noninvasive scores]]


==Treatment==
==Treatment==
Trials are presently being conducted to optimise treatment of NASH. No standard treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.<ref name=Adams/>
[[Non-alcoholic fatty liver disease medical therapy|Medical Therapy]] | [[Non-alcoholic fatty liver disease surgery|Surgery]] | [[Non-alcoholic fatty liver disease primary prevention|Primary Prevention]] | [[Non-alcoholic fatty liver disease secondary prevention|Secondary Prevention]] | [[Non-alcoholic fatty liver disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Non-alcoholic fatty liver disease future or investigational therapies|Future or Investigational Therapies]]


A large number of treatments have been studied for NAFLD. While many may improve biochemical markers, such as [[alanine transaminase]] levels, most have not been shown to reverse the histological abnormalities or reduce clinical endpoints:<ref name=Adams/>
==Case Studies==
* Weight loss: gradual weight loss, and possibly [[bariatric surgery]], may improve the process in obese patients.
* Insulin sensitisers ([[metformin]] and [[rosiglitazone]] but more markedly [[pioglitazone]]) have shown efficacy in some studies.
* [[Antioxidants]] and [[Ursodiol|ursodeoxycholic acid]], as well as lipid-lowering drugs, have little benefit.


==History==
[[Non-alcoholic fatty liver disease case study one|Case #1]]
NASH was described in 1980 in a series of patients of the [[Mayo Clinic]]<ref>Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434-438. PMID 7382552.</ref>. Its relevance and high prevalence were recognized mainly in the 1990s.


== References ==
==External Links==
<references/>
* [http://digestive.niddk.nih.gov/ddiseases/pubs/nash/ NIH] page on Nonalcoholic Steatohepatitis


==External links==
* [http://www.medscape.com/viewarticle/458509_1 Medscape] article on NASH.
* [http://www.medicinenet.com/fatty_liver/article.htm MEDICINENET] article on Steatosis.
* [http://digestive.niddk.nih.gov/ddiseases/pubs/nash/ NIH] page on Nonalcoholic Steatohepatitis


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{{Gastroenterology}}
{{Gastroenterology}}


[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Hepatitis]]
[[Category:Hepatology]]
[[Category:Disease]]


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Latest revision as of 15:59, 27 January 2024

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

For the patient information page on this topic, click here.

Synonyms and keywords: NASH, NAFLD, non-alcoholic steatohepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD)

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Non-Alcoholic Fatty Liver Disease from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies | Noninvasive scores

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

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Case #1

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