This document discusses liver enzyme tests, what they measure, normal ranges, and their clinical significance in evaluating liver health and disease. It focuses on aminotransferases ALT and AST, which are released when liver cells are damaged and are markers of hepatocellular injury. Elevations in ALT are more specific to the liver, while AST is also found in other tissues. The ratio of AST to ALT and the magnitude of elevation provides clues to different liver diseases.

1. Gary Oh

2.  Blood tests commonly obtained to evaluate the health of the liver include:
 Liver enzyme levels (ALT/AST)
 Hepatic synthetic function (Albumin/PT/PTT)
 Serum bilirubin level (Conjugated and Unconjugated bilirubin).
 Elevated liver enzymes reflect damage to liver or biliary tree obstruction
 Abnormal serum albumin or prothrombin time may be seen in the setting of
impaired hepatic synthetic function.
 Serum bilirubin partly measures liver's ability to detoxify metabolites and
transport organic anions into bile.
 Alanine aminotransferase (ALT):
• Male: 10 to 55 int. unit/L
• Female: 7 to 30 int. unit/L
 Aspartate aminotransferase (AST):
• Male: 10 to 40 int. unit/L
• Female: 9 to 32 int. unit/L

3. Liver Enzymes
Serum aminotransferases:
alanine aminotransferase (ALT, formerly called SGPT)
aspartate aminotransferase (AST, formerly called
SGOT)
Alkaline phosphatase (Alk Phos)
Gamma-glutamyl transpeptidase (GGT)
5'-nucleotidase
Lactate dehydrogenase (LDH)

4. First step is transamination, where amino group is
transferred a-KG
Products are alpha-keto acid (derived from the original
amino acid) and glutamate.
Glutamate produced by transamination can be oxidatively
deaminated, or used as an amino group donor in the
synthesis of nonessential amino acids.
Transaminases are in the cytosol and mitochondria of cells
throughout the body – (esp: liver, kidney, intestine, and
muscle).
All amino acids, with the exception of lysine and
threonine, participate in transamination at some point in
their catabolism.

5.  Substrate specificity of aminotransferases:
 Aminotransferases are named after the specific amino group donor,
 Acceptor of the amino group is almost always a-KG.
 Two most important aminotransferase reactions are catalyzed by alanine
aminotransferase (ALT) and aspartate aminotransferase(AST
 Alanine aminotransferase (ALT) (glutamate-pyruvate transaminase)
 ALT is present in many tissues. HOWEVER IT IS SPECIFIC FOR LIVER (unlike
AST which is present in many tissues including muscle). THUS elevations in
ALT are more specific for liver than AST.
 Catalyzes transfer of the amino group of alanine to a-KG, resulting in the
formation of pyruvate and glutamate.
 Reversible
 During amino acid catabolism, this enzyme functions in the direction of
glutamate synthesis.
 Glutamate, in effect, acts as a “collector” of nitrogen from alanine.
 Transfer of amino group between alanine and alpha keto acid forming
Pyruvate and Glutamate

7. Aspartate aminotransferase (AST):
AST is an exception to the rule that aminotransferases
direct amino groups to form glutamate.
AST transfers amino groups from glutamate to
oxaloacetate (forming aspartate), which is used as a
source of nitrogen in the urea cycle.
Reversible
Transfer of amino group between aspartate and alpha
keto acid forming OA and Glutamate.
Aspartate used in the urea cycle.

9. Liver Disease
Aminotransferases are intracellular enzymes
Low levels found in the plasma represent the release
of cellular contents during normal cell turnover.
Elevated plasma levels of aminotransferases indicates
damage to cells rich in these enzymes.

10. AST:ALT Ratio
Most causes of hepatocellular injury are associated with an AST that is
lower than the ALT.
Normal AST/ALT is 1.3
AST to ALT ratio of 2:1 or greater suggests alcoholic liver disease,
particularly in the setting of an elevated GGT.
Nonalcoholic steatohepatitis - AST to ALT ratio is elevated in an
alcoholic liver disease pattern in patients
Alcoholic liver disease – Elevated
Hepatitis C - Elevated
In addition, patients with Wilson disease or cirrhosis (viral hepatitis)
may have AST>ALT, though in patients with cirrhosis the ratio
typically is not greater than two.

11. Magnitude of AST and ALT elevations
 Magnitude of AST and ALT elevations varies due to cause of hepatocellular
injury
 Alcoholic fatty liver disease: AST <8 times the upper limit of normal; ALT <5
times the upper limit of normal
 Nonalcoholic fatty liver disease: AST and ALT <4 times the upper limit of
normal
 Ischemic hepatopathy (ischemic hepatitis, shock liver): AST and ALT >50
times the upper limit of normal (in addition the lactate dehydrogenase is often
markedly elevated)
 Acute viral hepatitis or toxin-related hepatitis with jaundice: AST and ALT >25
times upper limit of normal
 Chronic hepatitis C: Wide variability, typically normal to less than twice the
upper limit of normal, rarely more than 10 times the upper limit of normal
 Chronic hepatitis B: Levels fluctuate; the AST and ALT may be normal, though
most patients have mild to moderate elevations (approximately twice the
upper limit of normal); with exacerbations, levels are more than 10 times the
upper limit of normal

12. References
 Cohen JA, Kaplan MM. The SGOT/SGPT ratio--an indicator of alcoholic liver disease.
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 Fuchs S, Bogomolski-Yahalom V, Paltiel O, Ackerman Z. Ischemic hepatitis: clinical and
laboratory observations of 34 patients. J Clin Gastroenterol 1998; 26:183
 Gitlin N, Serio KM. Ischemic hepatitis: widening horizons. Am J Gastroenterol 1992;
87:831.
 Henrion J, Schapira M, Luwaert R, et al. Hypoxic hepatitis: clinical and hemodynamic
study in 142 consecutive cases. Medicine (Baltimore) 2003; 82:392.
 Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45:507
 Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the
United States population. Hepatology 2012; 55:447.