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(Established in March 1996)
Dr. Wu's Liver diseases
|Fatty liver and Nonalcoholic Steatohepatitis (NASH)/Nonalcoholic Fatty Liver Disease|
for professionals (medical students and residents)
(Posted Sep. 16, 1996; Updated May 14, 2009)
Fatty Liver, NASH, NAFLD
(Key words: fatty liver; hepatic steatosis; lipid; faty metamorphosis; triglycerides; steatohepatitis; nonalcoholic steatohepatitis (NASH); nonalcoholic fatty liver disease (NAFLD)
- A condition of an accumulation of excess fat in the liver.
- When the fat amount exceeds 5 % of the total weight or more than 30% of liver cells in a liver lobule are with fat deposit, it is diagnosed as fatty liver.
- Fatty liver is frequently observed in alcoholics, obese persons, and diabetic patients. It also occurs with certain drugs (such as: corticosteroids), viral hepatitis, chemical intoxication, pregnancy, intestinal bypass surgery and malnutrition etc.
- Eating fatty food by itself does not produce a fatty liver.
- It usually does not present symptoms. Rarely, it causes jaundice, nausea, vomiting, pain, and abdominal tenderness.
- It is usually diagnosed clinically by ultrasonographic (ultrasound) examination of the liver, for more detail examination it needs to be identified by taking a sample of liver tissue (liver biopsy) and examining it under a microscope.
- The mere presence of excessive fat in the liver is usually not a serious problem. However, fatty liver with inflammation (steatohepatitis) may eventually progress to cirrhosis and finally hepatocellualar carcinoma.
- Fatty liver induced due to excess alcohol intake (Alcoholism) could result in inflammation of the liver (alcoholic hepatitis) and scarring (alcoholic cirrhosis), and it is called "Alcoholic liver disease" .
- A condition of fatty liver with inflammation occurs in individuals without a history of excessive alcohol intake is called "Nonalcoholic steatohepatitis (NASH)". And the diagnosis of "Nonalcoholic fatty liver disease (NAFLD)" referrs to fatty liver, NASH and cirrhosis which ocurrs in an individual who has no history of excssive alcohol intake and withoout any identifiable cause of liver diseases mentioned above.
- In the past, the typical NASH patient was described as a middle-aged, obese persons (Female>Male) with excess sugar in the blood, which may have been caused by diabetes mellitus. The patient may have had excess fat in the blood.
- However, it has recently been reported that patients with NASH do not always fit this description. One study included men, as well as women, who were not overweight, did not suffer from diabetes mellitus, and did not have excess lipids (fat) in their blood.
- Recent studies indicate that NASH can result in the development of fibrous tissue in the liver (fibrosis) in up to 40% of
patients or cirrhosis in 5-10% of patients. It is not certain why some NASH patients will progress to this serious form of chronic liver disease while others do not.
- Treatment aims at elimination of the cause or treatment of the underlying disorders.
- Refer to "fatty liver" in Merck Manual - Home editioon".
- Refer to "Anatomical drawings - Digestive system - Merck Manual - Home edition" in Merck manual-Home editioon".
- Refer to "What is NAFLD/NASH? " in American liver foundation website.
- Fatty liver means a condition of accumulation of fat (lipid) inside liver cells in excess.
- Fat accounts around 5% of the total weight of normal liver, and when it exceeds 5 % of the total weight or more than 30% of liver cells in a liver lobule are with fat deposit, it is diagnosed as fatty liver.
- Fat accumulating in the liver is mainly in the form of triglycerides and fatty acids, and also is present in small amounts in the form of cholesterol, cholesterol ester and phospholipids.
- Fatty liver is designated pathologically as "fatty degeneration of the liver", and is also called as "fatty change, fat infiltration, fat metamorphosis or steatosis of the liver". These terminology may have precisely their own specific meaning, but generally they are used to mean fat accumulation in the liver.
- Histologic findings of fat deposit in the liver is different by the size and distribution of the fat in hepatic cells.
- In macrovesicular type, hepatocytes contain a large fat droplet with eccentric displacement of nucleus.
- In microvesicular type, hepatocytes contain multiple small droplets with nuleus at the center.
- Many microvesicular droplets with swelling of the cytoplasm is called foamy fatty degeneration.
- Fig: 1 (Hepatic pathology, University of Utah); Fig: 2(Hepatic pathology, University of Utah).
- Type and etiology of fatty liver:
- In alcoholic fatty liver, mixed type of macrovesicular and foamy fatty degeneration in the perivenular region is the usual histological finding.
- Microvesicular type is observed in acute fatty liver of pregnancy, tetracycline intoxication and Rey's syndrome.
- Macrovesicular type is frequently seen in fatty liver in metabolic syndrome.
- Fatty liver is noticed in a multitude of condition such as: obesity, alchoholic liver disease, diabetes mellitus, congestive heart failure, drug intoxication, pregnancy, Rey's syndrome, malnutrition (Kwashiorkor), chronic hepatitis, metabolic syndrome and cirrhosis of different etiology.
- Fatty liver is also called hepatic steatosis, and fatty liver with liver inflammation is called steatohepatitis. Steatohepatitis not caused by alcohol and any identifiable cause mentioned above is referred to as non-alcoholic steatohepatitis or "NASH.".
- The diagnosis was made by pathological examination of the biopsied liver tissue before the introduction of non-invasive image diagnostic means.
- It becomes easy and non-invasive after the practical use of image diagnosis, especially abdominal ultrasonographic examination.
- Therefore, the liver biopsy is usually avoided in the diagnosis of fatty liver in recent years.
- At present, the diagnosis is usually made by non-invasive means of ultrasonographic examination and CT of the abdomen if needed.
- For detail examination and exact diagnosis, the pathological examination of the biopsied liver tissue is necessary.
- Serum transaminase in fatty liver:
- In most frequently seen fatty liver due to obesity, the serum biochemical examination shows only mild elevation of GPT and GOT, usually GPT > GOT, and no other remarkable biochemical changes will be observed.
- The elevation of GPT is usually below 80 IU, but occasionally higher value may be observed, even up to higher than 150 IU. In this occasion, steatohepatitis should be taken into consideration.
- However in fatty liver of alcoholic origin and cirrhosis of any origins, GOT > GPT is common.
- In the obesity related fatty liver, the serum gamma-glutamyl transpeptidase (GGTP) is usually within the normal limits, and the elevation of GGTP is rather indicative of alcoholic origin in nature.
- If there are any other biochemical changes, a specific cause of fatty liver should be studied.
- The fatty liver due to obesity, and alcoholic origin is a reversible change, and for the treatment, the specific cause should be eliminated first.
- Obesity is a complex disease which results from the interaction of multiple genes and the environment. The recently discovered gene (ob gene) for secretion of leptin, regulating inhibition of appetite and promoting energy consumption, and the leptin receptor appear to play a major regulatory role in body energy balance and adipose tissue deposition.
- Leptin, a cytokine secreted by fat cells, is a product of obese gene, being concerned in the inhibition of eating and promotion of energy consumption through the mediation of receptor in the hypothalamus. It is worthwhile to observe the effects of leptin administration to patients with fatty liver caused by hyperalimentation. (Obesity and Leptin.)
- A Yale University researcher M. Rocio Sierra-Honigmann reported in "Science" the first time that leptin has been shown to have a function outside the brain, where it acts to suppress appetite. The report shows fat cells secrete the appetite-suppressing hormone leptin to promote development of the blood vessels they need to get oxygen and nutrients. Many cancers secrete other hormones that cause blood vessels to grow, and the research suggests the possibility of leptin among one of them. (Science, 281:1683~1686, 1998)
- The fatty liver can be classified by the type of distribution of fat depositted hepatocytes in the liver.
- 1. Diffuse type fatty liver:
Fat deposit is seen diffusely all over the liver.
- 2. Non-diffuse type fatty liver:
- Type I: Focal spared type:
Localized area with low fat deposit is seen in diffusely fat-depositted area.
- Type II: Segmental type or Geographic type:
Localized fat deposit areas are seen here and there with map-like appearance.
- Type III: Focal fatty change:
Some fat deposit areas are seen in non-fat-depositted region, looking like tumor lesions.
- Ultrasonographic findings:
- 1. Bright liver. (increased echo level)
- 2. Liver-kidney contrast. (increase liver echo level as compared to kidney)
- 3. Vascular blurring. (blurring of hepatic vein)
- 4. Deep attenuation. (attenuation of echo level in deep region)
- Rrefer to "Fatty liver" in Merck manual
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(By Jau-Shin Wu, M.D.; Posted Sep. 16, 1996; Revised May 12, 2009)
(TMN) Since June 09, 2002
(Dr. Wu's Liver D) Since Jan. 01, 2008
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