hepatic steatosis

脂肪肝

WordNet

1. pertaining to or affecting the liver; "hepatic ducts"; "hepatic cirrhosis"

PrepTutorEJDIC

1. 肝臓の;肝臓にきく,肝臓のような色の

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/24 16:45:29」(JST)

wiki en

[Wiki en表示]

Not to be confused with foie gras.

Fatty liver
Classification and external resources
Micrograph showing a fatty liver (macrovesicular steatosis), as seen in non-alcoholic fatty liver disease. Trichrome stain.
ICD-10	K70, K76.0
ICD-9	571.0, 571.8
DiseasesDB	18844
eMedicine	med/775 article/170409
MeSH	C06.552.241

Different stages of liver damage

Fatty liver, also known as fatty liver disease (FLD), is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis (i.e. abnormal retention of lipids within a cell). 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 metabolism. Morphologically, 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 (hepatitis), called steatohepatitis. By considering the contribution by alcohol, fatty liver may be termed alcoholic steatosis or nonalcoholic fatty liver disease (NAFLD), and the more severe forms as alcoholic steatohepatitis (part of alcoholic liver disease) and Non-alcoholic steatohepatitis (NASH).

Causes

Fatty liver is commonly associated with alcohol or metabolic syndrome (diabetes, hypertension, obesity and dyslipidemia), 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 (e.g., phosphorus, mushroom poisoning)

Other

Inflammatory bowel disease, HIV, hepatitis C (especially genotype 3), and alpha 1-antitrypsin deficiency

Pathology

Micrograph of periportal hepatic steatosis, as may be seen due to steroid use, trichrome stain

Fatty change represents the intracytoplasmic accumulation of triglycerides (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 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 (macrovesicular fatty change). 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.

Mechanism leading to hepatic steatosis

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 (PPAR-α, PPAR-γ and SREBP1) 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.

Micrograph of inflamed fatty liver (steatohepatitis)

Severe fatty liver is sometimes accompanied by inflammation, a situation referred to as steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or Non-alcoholic steatohepatitis (NASH) 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 (retention of lipid) 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

Liver steatosis (fatty liver disease) as seen on CT

Flow chart for diagnosis, modified from
Elevated liver enzyme                                 Serology to exclude viral hepatitis                                 Imaging study showing fatty infiltrate                                 Excess alcohol intake                                             Less than two drinks per day‡   More than two drinks per day‡                             Nonalcoholic fatty liver disease likely   Alcoholic liver disease likely
‡ Criteria for nonalcoholic fatty liver disease: consumption of ethanol less than 20g/day for women and 30g/day for men

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 (AST:ALT more than 2:1).

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 (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

The treatment of fatty liver depends on its cause, 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 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 will progress 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
• Non-alcoholic fatty liver disease
• Metabolic syndrome
• Alcoholic liver disease
• Cirrhosis
• Focal fatty liver

References

External links

• American Association for the Study of Liver Diseases
• American Liver Foundation
• [1]
• 00474 at CHORUS
• Photo at Atlas of Pathology

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人における非アルコール性脂肪性肝疾患（NAFLD）の疫学、臨床的特徴、および診断 epidemiology clinical features and diagnosis of nonalcoholic fatty liver disease in adults
• 2. 成人における非アルコール性脂肪肝疾患の自然経過およびマネージメント natural history and management of nonalcoholic fatty liver disease in adults
• 3. アルコール性脂肪性肝炎およびアルコール性肝硬変の臨床症状および診断 clinical manifestations and diagnosis of alcoholic fatty liver disease and alcoholic cirrhosis
• 4. 妊娠時の急性脂肪肝 acute fatty liver of pregnancy
• 5. 非アルコール性脂肪性肝疾患の病因 pathogenesis of nonalcoholic fatty liver disease

English Journal

• The increased activity of liver lysosomal lipase in nonalcoholic Fatty liver disease contributes to the development of hepatic insulin resistance.

• Cahova M, Dankova H, Palenickova E, Papackova Z, Komers R, Zdychova J, Sticova E, Kazdova L.SourceDepartment of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech Republic.
• Biochemistry research international.Biochem Res Int.2012;2012:135723. Epub 2011 Aug 23.
• We tested the hypothesis that TAG accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally linked with the onset of hepatic insulin resistance. We found that L
• PMID 21904679

Japanese Journal

• 肝脂肪化と炎症・インスリン抵抗性をつなぐ分子メカニズム--ヘパトカインセレノプロテインPによるインスリン抵抗性・高血糖の誘導 (特集 NASH/NAFLD発症のメカニズム)

• 御簾 博文
• 消化器内科 52(5), 515-518, 2011-05
• NAID 40018891065

Related Links

• Hepatic steatosis - definition of Hepatic steatosis in the Medical ...

Fatty liver is the collection of excessive amounts of triglycerides and other fats inside liver cells. Description. Also called steatosis, fatty liver can be a temporary or long-term condition, which is not harmful itself, but may indicate some other type ...

Related Pictures

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★リンクテーブル★

リンク元	「脂肪肝」「liver steatosis」
関連記事	「hepatic」

「脂肪肝」

　　[★]

英

fatty liver、steatosis、hepatic steatosis、liver steatosis

関

脂肪過多症、脂肪症、アルコール性肝障害

概念

• 脂肪滴を含んだ肝細胞が、小葉の1/3以上に及んだ病態で、肝臓全体としては脂肪が10%以上蓄積する(正常2-4%)。
• おそらく、脂肪肝(＝？非アルコール性脂肪性肝疾患 nonalcoholic fatty liver disease NAFLD)は高位の概念で、この中に非アルコール性脂肪肝炎 NASHが含まれ、NASHはNASLDの極端な病態(障害が高度という意味か)である。(参考1)

病態生理

see BPT.654 uptodate.2

原因

YN.B-36改変 uptodate.1

• 栄養不良状態：クワシオルコル
• 過剰栄養摂取・状態

• アルコール多飲：大酒家の80%以上で合併
• 肥満：BMI 25以上で30%以上、30以上で80%に合併
• 糖質過剰摂取、糖尿病、過剰高カロリー輸液

• 内分泌・代謝異常

• 甲状腺機能亢進症　　←　　高トリグリセリド血症となるため(uptodate.1)
• クッシング症候群

• 薬剤性

• 副腎皮質ステロイド、テトラサイクリン系抗菌薬

• 妊娠：急性妊娠脂肪肝
• その他

• ペラグラ
• ライ症候群

検査

• 血液検査

• AST・ALT：正常かやや上昇(ALT優位) (YN.B-36)　⇔　アルコール性脂肪肝ではAST優位

思うに、小葉辺縁(門脈域)にはALTが多いが、脂肪滴を蓄えた肝細胞はこの領域に多いのでは？だとすれば、lipid peroxidation productによる肝障害によりALTがleakしてALT優位となる説明がつくのだが。どうなの？

CT

• 脂肪肝：単純CTで肝実質のCT値が脾臓よりも低くなる。正常な肝臓は脈管より高CT値を示すが、脂肪肝の場合はより低CT値を示すようになる

肝臓CT値低下の鑑別診断：肝炎に伴う浮腫、肝臓の線維化、腫瘍浸潤(悪性リンパ腫、びまん性肝細胞癌)、アミロイドーシス

==参考==liver disease - wiki en

http://en.wikipedia.org/wiki/Non-alcoholic_fatty_liver_disease

uptodate

• 1. [charged] 成人における甲状腺機能亢進症の臨床症状の概要 - uptodate [1]
• 2. [charged] 非アルコール性脂肪性肝疾患の病因 - uptodate [2]

「liver steatosis」

　　[★]

• 脂肪肝

• 肝細胞内に多量の中性脂肪が蓄積した状態

関

fatty liver、hepatic steatosis、steatosis

「hepatic」

　　[★]

• adj.

• 肝臓の、肝性の、肝の

関

hepato、hepatogenic、liver