• GOT (Glutamyl oxaloacetic transaminase)

• GPT (Glutamyl pyruvic transaminase)

• AST (Aspartate aminotransferase)

• ALT (Alanine aminotransferase)

• One of the thousands kinds of liver enzymes, and a kind of transferase.

• Having the function of transfering amino group of amino acids from alpha-amino acids to alpha-keto acids, therefore, named transaminase.

• L-Aspartic Acid + Ketoglutaric Acid ¡÷ Oxaloacetic Acid + L-Glutaric Acid

• L-Alanine + Ketoglutaric ¡÷ Pyruvic Acid + Glutaric Acid

• Storage mostly in liver etc.

• Low serum concentration.

• Large amount of transaminase is released into blood mostly on liver cell damages.

• Thus, detection of serum level tells the existence of liver cell damage.

• mainly due to damages of liver, myocardium, striated muscle and red blood cells.

  Table: Concentration in organs and tissues.

  Organs	GOT	GPT
  Myocardium	156,000	7,100
  Liver	142,000	44,000
  Kidney	99,000	4,800
  Pancreas	28,000	2,000
  Spleen	14,000	1,200
  Lung	10,000	720
  Red blood cell	300	110
  Serum	20	16

  According to Wroblewski and La Due (Karmen unit/1 gm wet weight)

  • In 1954, La Due first reported the elevation of serum GOT in acute myocardial infarction.

  • In 1955, De Ritis reported the elevation of serum GOT and GPT in hepatitis.

  • It has been used as the marker of liver damage since then until now.

  • GOT exist maily in liver and myocardium, and in less amount in kidney and pancreas.

  • The concentration of GOT and GPT are 1,000 ~ 10,000 times of serum.

  • In liver or cardiac damages large amount of transamionase are released into serum, therefore, it shows very high sensitivity in the detection of liver and cardiac damages.

  • GPT is more sensitive and specific than GOT in the detection of liver disease.

  • Injuries with myocardium is localized and with liver diffuse and massive, thus the extent of elevation of serum transaminase is quite different, moreover, the cardiac disease usually has more specific and remarkable symptoms that it will be of little difficulty in differential diagnosis between liver and cardiac diseases in case of elevated serum transaminase.

Objects and usefulness

• Of use in detection of asymptomatic stage in liver disease as: preicteric stage of hepatitis.

• Of use in detection of anicteric liver disease.

• Useful in evaluation of the course of liver disease.

• Determining factors of serum levels:
  • Tissue concentration of transaminase.

  • Extent of tissue damages.

  • Capability of release of enzyme from the tissues.

  • Half life of the transaminase in the blood.

• GOT:
  • Karmen method: 10 ~ 26 KU

  • Reitman-Frankel method: 7 ~ 20 KU

  • JSCC, IFCC: 15 ~ 40 IU/L

• GPT:
  • Karmen method: 3 ~ 18 KU

  • Reitman-Frankel method: 2 ~ 17 KU

  • JSCC, IFCC: 8 ~ 30 IU/L

• GOTm:
  • Immuno-absorption method: < 4 KU

• (The result may be expressed with IU, international unit)

• KU/IU: 1.35 ~ 1.58 (depend on methods)

• As serum GOT is below 30 KU and GPT 25 in 90 % of healthy persons, we usually assume 40 IU for GOT and 35 IU for GPT as their upper limits of normal.
• GOT/GPT: (depends on method, 0.7 ~ 1.4):1 by Karmen method, 0.87 by JSCC.
• Age influence:

• GOT: lowest under the age of 20 years for both sexes, thereafter, increases with the increase in age.
• GPT: highest at the ages of 30 ~ 40 years for male, and 50 ~ 60 years for female.
• No influenced by food.
• Increase after exercise.
• Increase in hemodialysis, and GOT > GPT.
• Preservation of specimens:

• Rather stable with GOT.
• At 4¢J, with little change for one week.
• Under freezing, no change for one month.
• GPT is somewhat unstable than GOT.
• At 4¢J, stable for only 3 ~ 4 days.
• Under freezing: without change for 2 weeks.
• With higher concentration of the serum level, it shows rather unstable effect, thus it is advised to make the test on the day when the blood is drawn, and even the serum is kept frozen , the test should be done within 5 days after blood is obtained.

A) Hepatobiliary diseases:

1) Acute hepatitis:

• Whatever the etiological factors is, when there is liver cell injuries, there will be of increase in serum transaminase levels.

• At the onset, the serum level may increase up to as high as 300 ~ 3,000 units.

• Sometimes, the level may as high as over 3,000 units, however, it is around 500 ~ 1,500 units in most of the cases.

• Even in the absence of jaundice, the level may rise high up to over 1,000 units.

• When a test is done immediately after the onset, the level of GOT is usually higher than GPT.

• After the peak stage (usually, one week after the onset of symptoms), the level of GPT will be greater than GOT (GPT > GOT).

• In general practice, the serum GPT level is usually greater than GOT and below 1,000 units at the first test on consultation, because the patients usually consult with the physician more than one week after the onset of symptoms.

• Moreover, the serum transaminase level might have lowered to the level of within normal range, thus the physician often hesitate to make the diagnosis of hepatitis.

• Histopathological change of acute hepatitis will be observed on the liver biopsy examination in spite of the normal serum transaminase level for these cases.

• In typical course of acute hepatitis cases, the serum transaminase will recover to the normal range within 6 ~ 10 weeks.

• In cases with serum transaminase level rises and falls between 100 ~ 300 units for more than three months, chronic hepatitis should be considered.

• In acute hepatitis, change of serum GOT and GPT is great and rapid during the first 10 days after the onset of symptoms. At the time of onset of jaundice, the levels of serum GOT and GPT have already begun to decrease, therefore, when the patient presenting with the symptoms suspicious of the possibility of hepatitis, you should test the blood for serum transaminase, because if you draw blood a few days later, the serum transaminase might have decreased and be difficult to be used as the marker for diagnosis of hepatitis.

• For instance, it is not uncommon that the patient consults the physician on Saturday, however, the drawing of blood is delayed until next Monday because of weekend, and as a result the serum transaminase level may have dropped to the level of below 200 units, which confuses you to make a differential diagnosis between hepatitis and obstructive jaundice.

• At times, in a case of fulminant hepatitis, the serum transaminase level may have already dropped to the level of normal range on presentation, which may mislead physician to the diagnosis of ordinary acute hepatitis but not a fulminant hepatitis.

• The large amount of transaminase released to the blood stream in a case of fulminant hepatitis is removed from blood in a few days, and the massive necrosis caused few intact liver cells remained to supply as the source of serum transamninase.

• In the cases of mild chronic hepatitis (chronic persistent hepatitis), serum transaminase usually fluctuates below the level of 100 units.

• In the cases of moderate to severe chronic hepatitis (chronic active hepatitis), serum transaminase fluctuates between 100 ~ 300 units.

• Normal serum transaminase level does not always mean no active inflammation of the liver cells. It is not uncommon that active chronic hepatitis will be observed on histopathlogical examination.

• It is common that when a case of chronic hepatitis without subjective symptoms presenting himself with symptoms, serum transaminase level could be as high as over 1,000 units, thus it is impossible to differentiate between an acute hepatitis and an acute exacerbation of chronic hepatitis by the extent of rise in the level of serum transaminase.

• Serum transaminase usually fluctuates persistently in the range of below 100 IU.

• In cases of cirrhosis associated with the active chronic hepatitis, the serum transaminase level will be higher than those without active chronic hepatitis. Its range is the same as that of active chronic hepatitis.

• Usually, the serum GOT level is 5 ~ 6 times greater than serum GPT in cirrhosis patients. Therefore, it is often difficult to make differential diagnosis with a case of acute myocardial infarction without typical symptoms.

• The dissociation between GOT and GPT is explained as due to more highly differentiated GPT than GOT, which caused the more difficulty in synthesis of GPT than GOT owing to the circulatory failure in cirrhosis of the liver.

• The degree of elevation of GOT and GPT is unrelated to the extent of cirrhosis but related to the degree of the active inflammation of the liver.

• In the presence of active piecemeal necrosis in the periportal area and progressive infiltration of chronic inflammatory cells and liver cell damages in the hepatic lobules, the elevation of serum transaminase keep mild to moderate degree of elevation.

• In alcoholic fatty liver and cirrhosis of the liver, there will be of 75 % of the cases with elevation of serum GOT and GPT. In cases of fatty liver, the degree of elevation is usually below 100 IU, and in cases of cirrhosis, usually resembles to that of the cases of viral origin.

• In the cases of acute alcoholic hepatitis, around 95 % of the cases will show higher elevation of GOT and GPT, and it may be high up to 300 IU.

• In alcoholic liver disease, the ratio of GOT/GPT ratio is usually higher than 2, therefore in case with GOT/GPT ratio greater than 2, we should consider the possibility of alcoholic liver disease.

• It is explained as the result of decrease in pyridoxal-5'-phosphate, which is depressed in alcoholic liver disease, because pyridoxal plays an important role in the aminoacids metablolism (i.e. synthesis of transaminase), and GPT depends more on pyridoxal than GOT for its synthesis.

• It is also explained as the result of release of GOTm (mitochondrial GOT) from the liver cells around the central vein. In alcoholic liver disease, more liver cells around the central vein than peripheral region of the hepatic lobules are damaged, and more GOTm is present in the cells of this region.

• In my experience, among 32 cases of chronic alcoholics, the average serum GOT level is 134 IU, and GPT 50 IU, the highest values are 900 and 200 IU for GOT and GPT, respectively.

• All tumor lesions including malignancy of the liver (primary and metastatic) and localized liver lesion such as liver abscess show non-specific elevation of serum transaminase.

• May elevate up to 300 IU and usually GOT is greater than GPT.

• The elevation of serum GOT and GPT is mostly owing to the release of the enzymes from the surrounding liver cells due to the increasing pressure from the growing mass, and partly released from the malignant cell itself.

• In Taiwan, 80 % of the hepato-cellular carcinomas are arising on the basis of cirrhosis, therefore the elevated serum GOT and GPT reflect the active inflammatory process of the underlying cirrhotic change.

• In the cases with lesions limited in the gall bladder and without the involvement of bile ducts such as: cholecystitis, gall bladder stone and tumor of the gall bladder, not only serum GOT and GPT, but also the other liver related enzyme tests will be in the range of normal.

• In cases with involvement of bile ducts such as: cholangitis, obstruction due to stone, tumor or parasite, the serum GOT and GPT will be of mild to moderate degree of elevation, rarely over 300 IU, and GOT is usually greater than GPT. The elevation above 300 IU is exceptional.

• Except for in the cases of hepato-biliary diseases, the elevation of serum GOT will be observed in the diseases of heart and striated muscle, however, no concomitant elevation of GPT will be noted.

• Myocardium contains the same concentration of GOT as that of the liver, therefore, in case of injury to the myocardium as in the acute myocardial infarction, the GOT released from the damaged myocardium makes serum GOT elevated. The ratio of GOT concentration in the serum and myocardium is 1: 7,800, and the volume of serum in an adult is about 2,000 cc, thus even only 0.25 gm of myocardium had the damage, it would double the serum concentration of GOT but not GPT.

• In typical case of acute myocardial infarction, serum GOT would rise 6 ~ 12 hours after the onset of attack, and reaches the highest level in 24 ~ 48 hours after the onset. This elevation would recover to within normal range in 3 ~ 5 days after.

• In acute myocardial infarction, the serum GOT rarely exceed the level of 500 IU.

• In patients with cardiac symptom associated with elevation of GOT more than 500 IU and also accompanied by elevation of GPT, a right heart failure or shock state should be considered.

• Because, the cardiac disease has quite distinct clinical symptoms, the differential diagnosis seldom becomes a problem.

• In striated muscular diseases as: polymyositis, progressive muscular dystrophy and dermatomyositis, increase in serum GOT is observed.

• Only increase in serum GOT is observed, but not associated with concurrent increase in serum GPT.

• Serum creatine phosphokinse (CPK) increases markedly in striated muscular diseases, but no increase of CPK is observed in liver diseases, this observation usually makes the differential diagnosis easy.

• In shock state, a large amounts of GOT and GPT are released to the blood stream due to the central necrosis of the hepatic acinus.

• Elevation of serum GOT may be induced from hemolytic diseases and hemolysis due to any causes.
  

• GPT is contained only in cytosol of cells, but GOT present in both cytosol and mitochondria of the cells, therefore, there are two sorts of GOT, i.e. GOTm (mitochondrial) and GOTs (supernatant).

• Only GOTs is released, when only degeneration or changes in permeability of the liver cell membrane occur, however, when massive necrosis of the liver occur, there will be of release of a large amount of GOTm into the blood stream from the destructed liver cells, therefore, by determination of ratio of serum GOTm and GOTs, the degree of liver cell injuries will be estimated.

• In alcoholic liver disease, the liver cell necrosis occurs mostly in the perivenular region where GOTm is abundant, therefore, a remarkable increase of GOTm will be noted in alcoholic liver disease.

(Dr. Wu's Liver D) Since Jan. 01, 2008

(Olddoc)Since Jan. 01, 2008

(TMN) Since Jan. 01, 2008