Alanine Aminotransferase (ALT)

Alanine aminotransferase (ALT) 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 the 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 3,000 fold higher than in plasma. Measurement of plasma ALT activity is a good indicator of hepatocyte injury. 

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 and peaks near the onset of jaundice in viral hepatitis. Activity falls slowly, an average of 10% per day.  ALT remains elevated 27 +/- 16 days. 
• ALT levels fluctuate between normal and abnormal in hepatitis C. Between 15 and 50% of patients with chronic hepatitis C have persistently normal levels of 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. Ninety percent of cases with ALT >3,000 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 plasma 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.

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%.  

In 2021, the upper reference limits for ALT were redefined as 42 U/L in men and 30 U/L in women. For children, the reference ranges were 30-38 U/L for boys and 24-32 U/L for girls. 

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. 

References

Leung KK Hirschfield GM, Elevated Serum Aminotransferases, JAMA, Feb 8, 2022;327:580-581.

Kwo Py, et al. clinical Guideline: evaluation of abnormal liver chemistries. Am J Gastroenterologist. 2017;112:18-35.