Alanine Aminotransferase (ALT) Is Also Known As Serum Glutamic Pyruvic Transaminase (SGPT)

AlanineAminotransferase(ALT) (SGPT)

Alanine aminotransferase (ALT) is also known as serum glutamic pyruvic transaminase (SGPT).

• 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 (SGPT) activity is more specific for liver damage than increased AST or SGOT activity as ALT is seldom increased inheart or muscle disease.
• Until 15 to 20 years of age plasma ALT activity is lower than AST. Thereafter, plasma ALT activity tends to be higher than AST activity until age 60. After that 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 / PeakALT
x ULN / AST:ALT
Ratio / Peak Bilirubin / Protime
Prolongation
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.

ALT in viral hepatitis

• The best ALT discriminant value for recognizing acute hepatic injury is 300 U/L.
• ALT increases before appearance of jaundice & peak near onset of jaundice in viral hepatitis. Activity falls slowly, an average of 10% per day. ALT remains elevated for 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 patient’s condition. In fulminant hepatic necrosis, decreasing ALT may signify a paucity of viable hepatocytes rather than recovery.

Slightly raised serum ALT levels

Patients with cirrhosis, non-alcoholic steatohepatitis, cholestatic liver disease, fatty liver and hepatic neoplasm 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.

Medications cause abnormal aminotransferase levels

• Pain relief medicationssuch as: aspirin,acetaminophen,ibuprofen, naproxen, Nadiclofenac, andphenylbutazone
• Anti-seizure medicationssuch as: phenytoin,valproic acid, carbamazepine,andPhenobarbital
• Antibioticssuch as: tetracyclines, sulfonamides,isoniazid, sulfamethoxazole,nitrofurantoin,fluconazole and some other anti-fungals, etc.
• Cholesterollowering drugssuch as: thestatins: lovastatin,pravastatin,atorvastatin,fluvastatin, rosuvastatin, simvastatin, and niacin
• Cardiovascular drugssuch as:amiodarone, hydralazine,quinidine, etc.
• Other drugs Anti-depressant drugs of the tricyclic type

With drug-induced liver enzyme abnormalities, the enzymes usually normalize weeks to months after stopping the medications.

The medications most commonly associated with elevated ALT are *sulfonamides, *statins and *isoniazid.

In most types of liver disease, AST activity is lower than ALT.Exceptions include alcoholic hepatitis and Reye syndrome.

The ratio of AST to ALT in diagnosis of some liver diseases.

• In most patients with acute liver injury the ratio is 1 or less.
• In alcoholic hepatitis it is generally about 2. Deficiency of pyridoxal-5'-phosphate, a necessary coenzyme for both aminotransferases, is common in alcoholic liver disease. This deficiency decreases ALT to a greater extent than AST.
• In renal failure, AST and ALT are significantly lower than in healthy individuals, because of reduced availability of pyridoxal-5'-phosphate.

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%.

Specimen Required

Container/Tube:Plain, red-top tube(s) or serum gel tube(s)

Reject Due To

Specimens other thanSerum

HemolysisMild OK; Gross reject

Reference range is 20 - 60 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.

Investigations in asymptomatic patients with increased liver enzyme level

Level I

Test / Abnormality / Interpretation
Full blood count / Macrocytosis / Suggests alcohol excess if GGT also raised
Thrombocytopenia / Possible hypersplenism (portal hypertension)
Autoantibodies / AMA positive, IgM / Probable primary biliary cirrhosis
ASM/ANA positive, IgG / Strongly suggestive of autoimmune hepatitis
Ferritin / Elevated / Possible haemochromatosis, investigate further
Hepatitis B surface antigen / Positive / Implies chronic infection
Hepatitis C antibody / Positive / Suggests chronic infection

Level II

Test / Abnormality / Interpretation
Liver ultrasound / Mass/dilated ducts / Tumour/stones
Anti‐endomysial antibodies / Positive / Suggests coeliac disease
α1‐Antitrypsin level / Low / Suggests deficiency. Phenotype required (PiZZ or PiM implicated)
Others: for example, caeruloplasmin, urine copper as dictated by clinical context / Low / Wilson's disease

Adapted from the American Gastroenterology Association.

Level 1 suggested first investigation set;

Level 2, if no diagnosis obtained after Level 1.

AMA, antimitochondrial antibody; ANA, antinuclear antibody; ASM, anti‐smooth muscle actin monoclonal antibody; IgM, immunoglobulin M.J Clin Pathol.2006 December;59(12): 1229–1237.

Factors affecting AST and ALT activity, other than liver injury.

Factor / AST(SGOT) / ALT(SGPT) / Comments
Time of day / 45% variation during day; highest in afternoon,
lowest at night
Day-to-day / 5–10% variation from one day to next / 10–30% variation from one day to next / Similar in liver disease and health, and in elderly and young
Race/gender / 15% higher in African- American men / No significant difference between African-American, other women
BMI / 40–50% higher with high BMI / 40–50% higher with high BMI / , / Direct relationship between weight and AST, ALT
Meals / No effect / No effect
Exercise / Threefold increase with strenuous exercise / 20% lower in those who exercise at usual levels than in those who do not exercise or exercise more strenuously than usual / Effect of exercise seen predominantly in men; minimal difference in women (<10%). Enzymes increase more with strength training
Specimen storage / Stable at room temp for 3 days, in refrigerator for 3 weeks (<10% decrease); stable for years frozen (10–15% decrease) / Stable at room temperature for 3 days, in refrigerator for 3 weeks (10–15% decrease); marked decrease with freezing/thawing / Stability based on serum separated from cells; stable for 24 h in whole blood, marked increase after 24 h
Hemolysis, hemolytic anemia / Significant increase / Moderate increase attributable to release from red cell / Dependent on degree of hemolysis; usually severalfold lower than increases in LDH
Muscle injury / Significant increase / Moderate increase / Related to amount of increase in CK

Diagnosis and Monitoring of Hepatic Injury. I.Performance Characteristics of Laboratory TestsD. Robert Dufour,John A. Lott,Frederick S. Nolte,David R. Gretch,Raymond S. Koff,and Leonard B. Seeff Clinical Chemistry46: 2027-2049, 2000;

References

• W S A Smellie, J Forth, S Ryder, M J Galloway, A C Wood, and I D Watson Best practice in primary care pathology: review 5 J Clin Pathol. 2006 December; 59(12): 1229–1237.
• DAVID E. JOHNSTON, M.D.Special Considerations in Interpreting Liver Function Tests AAFP April 15 1999 2223-2233
• D. Robert Dufour,John A. Lott, Frederick S. Nolte,David R. Gretch,Raymond S. Koff,and Leonard B. Seeff Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests Clinical Chemistry 46:12 2027–2049 (2000)
• American Gastroenterological Association Medical position statement: evaluation of liver chemistry tests.Gastroenterology2002.1231364–1366
• Richard M.GreenStevenFlammAGA technical review on the evaluation of liver chemistry testsGastroenterology Volume 123, Issue 4, Pages 1367-1384
• Giannini E G, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians.CMAJ2005.172367–379.379.

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