Gary Oh

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

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'-nucleotidaseLactate dehydrogenase (LDH)

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.  

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

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.

Liver DiseaseAminotransferases are intracellular enzymesLow 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.

AST:ALT RatioMost causes of hepatocellular injury are associated with an

AST that is lower than the ALT. Normal AST/ALT is 1.3AST 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 patientsAlcoholic liver disease – ElevatedHepatitis 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.

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

References Cohen JA, Kaplan MM. The SGOT/SGPT ratio--an indicator of alcoholic liver

disease. Dig Dis Sci 1979; 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.