Download Alanine Aminotransferase (ALT)

Alanine Aminotransferase (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 in heart 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
Peak ALT
AST:ALT
x ULN
Ratio
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
Viral hepatitis
Peak Bilirubin
Protime
Prolongation
X ULN = times upper limit of normal,
Protime prolongation is number of seconds above ULN
ALT in viral hepatitis
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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.
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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
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Pain relief medications such as: aspirin, acetaminophen, ibuprofen, naproxen,
Nadiclofenac, and phenylbutazone
Anti-seizure medications such as: phenytoin, valproic acid , carbamazepine,
and phenobarbital
Antibiotics such as: tetracyclines, sulfonamides, isoniazid, sulfamethoxazole,
nitrofurantoin, fluconazole and some other anti-fungals, etc.
Cholesterol lowering drugs such as: the statins:
lovastatin, pravastatin, atorvastatin,fluvastatin, rosuvastatin, simvastatin, and niacin
Cardiovascular drugs such 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 than Serum
Hemolysis
Mild OK; Gross reject
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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)
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
Autoantibodies
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.
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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)
Time of day
45% variation during day;
highest in afternoon,
lowest at night
5–10% variation from one 10–30% variation from one
day to next
day to next
Day-to-day
ALT(SGPT)
Comments
Similar in liver disease and
health, and in elderly and
young
Race/gender 15% higher in AfricanNo significant difference
American men
between African-American,
other women
BMI
40–50% higher with high 40–50% higher with high BMI , Direct relationship between
BMI
weight and AST, ALT
Meals
No effect
No effect
Exercise
Threefold increase with 20% lower in those who
Effect of exercise seen
strenuous exercise
exercise at usual levels than in predominantly in men;
those who do not exercise or minimal difference in women
exercise more strenuously
(<10%). Enzymes increase
than usual
more with strength training
Specimen
Stable at room temp for 3 Stable at room temperature
Stability based on serum
storage
days, in refrigerator for 3 for 3 days, in refrigerator for 3 separated from cells; stable
weeks (<10% decrease); weeks (10–15% decrease);
for 24 h in whole blood,
stable for years frozen
marked decrease with
marked increase after 24 h
(10–15% decrease)
freezing/thawing
Hemolysis,
Significant increase
Moderate increase
Dependent on degree of
hemolytic
attributable to release from
hemolysis; usually
anemia
red cell
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 Tests D. Robert
Dufour,John A. Lott,Frederick S. Nolte,David R. Gretch,Raymond S. Koff,and Leonard B. Seeff Clinical
Chemistry 46: 2027-2049, 2000;
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References
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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. Gastroenterology 2002. 1231364–1366
Richard M. Green Steven Flamm AGA technical review on the evaluation of liver
chemistry tests Gastroenterology Volume 123, Issue 4 , Pages 1367-1384
Giannini E G, Testa R, Savarino V. Liver enzyme alteration: a guide for
clinicians. CMAJ 2005.172367–379.379.
Take home message
 Elevated ALT values are seen in liver diseases characterized by a destruction of hepatocytes.
 Twenty to fifty-fold elevations are most frequently encountered.
 In infectious hepatitis the ALT/AST ratio, which normally and in other condition is <1, becomes
greater than unity.
 ALT levels are usually elevated before clinical signs and symptoms of disease appear.
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