Alanine aminotransferase is an enzyme involved in the transfer of an amino group from the amino acid, alanine, to alpha-ketoglutaric acid to produce glutamate and pyruvate. ALT is located primarily in liver and kidney, with lesser amounts in heart and skeletal muscle. Increased ALT activity is more specific for liver damage than increased aspartate aminotransferase (AST) activity. ALT is seldom increased in patients with heart or muscle disease in the absence of liver involvement. In healthy children, plasma ALT activity is lower than AST until 15 to 20 years of age. Thereafter, plasma ALT activity tends to be higher than AST activity until age 60, when the activities become roughly equal. The half-life of ALT in the circulation is 47 +/- 10 hours.

ALT activity in the liver is 3000 fold higher than in serum. Measurement of serum ALT activity is a good indicator of hepatocyte injury.

Disease

Peak ALTx ULN

AST:ALTRatio

Peak Bilirubin

ProtimeProlongation

Viral hepatitis

10 – 40

<1

<15

<3

Alcoholic hepatitis

2 - 8

>2

<15

1 – 3

Toxic injury

>40

>1 early

<5

>5 transient

Ischemic injury

>40

>1 early

<5

>5 transient

X ULN = times upper limit of normal, Protime prolongation is number of seconds above ULN

  • The best ALT discriminant value for recognizing acute hepatic injury is 300 U/L.
  • ALT increases before & peak near onset of jaundice in viral hepatitis. Activity falls slowly, an avery of 10% per day. ALT remains elevated 27 +/- 16 days.
  • ALT levels fluctuate between normal and abnormal in hepatitis C. 15 to 50% of patients with chronic hepatitis C have persistently normal ALT.
  • In uncomplicated alcoholic hepatitis, ALT values are almost never >10 times the upper reference limit.
  • Extremely elevated ALT levels are common in toxic hepatitis and hepatic ischemia secondary to circulatory collapse and heatstroke. 90% of cases with ALT >3000 U/L are due to toxic or ischemic injury. AST is usually higher than ALT and both enzymes peak in the first 24 hours after admission. After peaking, both levels fall rapidly; AST faster than ALT.
  • Peak ALT levels bear no relationship to prognosis and may fall with worsening of the patients condition. In fulminant hepatic necrosis, decreasing ALT may signify a paucity of viable hepatocytes rather than recovery.

Patients with cirrhosis, non-alcoholic steatohepatitis, cholestatic liver disease, fatty liver and hepatic neoplasm typically have slightly raised serum ALT levels (<120 IU/L). Patients with cirrhosis seldom have ALT levels higher than two times normal. Cirrhotic patients without ongoing liver injury the values may have normal values.

Other causes of elevated ALT include hemochromatosis, Wilson disease, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis and alpha-1 antitrypsin deficiency. The medications most commonly associated with elevated ALT are sulfonamides, statins and isoniazid.

The ratio of AST to ALT in plasma may help in the diagnosis of some liver diseases. Most liver diseases are associated with greater elevation of ALT than AST because of the longer circulating half-life of ALT. Exceptions include alcoholic hepatitis, cirrhosis, Wilson disease and very early liver damage. In these disorders the AST to ALT ratio is generally greater than 2.

Both AST and ALT require vitamin B6 (pyridoxal-5'-phosphate, P5P) as a catalytic cofactor. Pyridoxal-5’-phosphate deficiency is common in alcoholic liver disease and renal failure.  In an attempt to standardize aminotransferase assays, the International Federation of Clinical Chemistry (IFCC) recommended that laboratories add excess P5P to their enzyme reagents so that these assay accurately measure enzyme activity independently of vitamin B6 status. Unfortunately, less than 50% of ALT assays incorporate exogenous 5P5.

In healthy individuals, ALT levels can vary 10 to 30% from one day to the next.  ALT levels can fluctuate 45% during a single day, with highest levels occurring in the afternoon and lowest levels at night.  A high body mass index can increase ALT levels by 40 to 50%. 

Reference range is 14 - 63 IU/L.

Specimen requirement is one SST tube of blood.  ALT is stable at room temperature for 3 days and refrigerated for 3 weeks.  Hemolysis causes moderate increases in ALT levels. 


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