Introduction:
The measurement of serum enzyme activity is one of the most valuable tools in diagnosing and managing liver diseases. Enzyme tests help identify tissue injury, evaluate liver function, and monitor disease progression. However, since many enzymes are present in multiple tissues, interpreting their rise or fall requires correlation with clinical findings and other biochemical tests.
The most commonly used enzyme tests for liver function include:
- Alkaline Phosphatase (ALP)
- Aspartate Aminotransferase (AST or GOT)
- Alanine Aminotransferase (ALT or GPT)
In specialized laboratories, additional enzymes like Gamma Glutamyl Transferase (GGT), 5’-Nucleotidase (NTP), Ornithine Carbamoyl Transferase (OCT), and isoenzymes of LDH or ALP are also measured for specific diagnostic purposes.
1. Serum Alkaline Phosphatase (ALP)
Alkaline Phosphatase (ALP) was one of the first enzyme tests used in differentiating types of jaundice and remains a useful test when interpreted with other liver function tests.
Reference Values:
- Normal range: 20 – 105 U/L (adults)
Clinical Significance:
- Increased ALP: Found in liver and bone disorders. Elevated levels are especially high in cholestasis (bile duct obstruction), hepatic tumors, or infiltrative diseases like carcinoma, tuberculosis, and sarcoidosis.
- Moderate Increase: Seen in hepatitis and cirrhosis.
- Marked Increase: (>2.5× ULN) seen in obstructive jaundice.
Since ALP also rises in bone diseases, its value in liver diagnosis increases when correlated with serum protein electrophoresis or other hepatic tests.
2. Aminotransferases: AST (GOT) and ALT (GPT)
The two most important aminotransferases for liver evaluation are:
- AST (Aspartate Aminotransferase): Found in liver, heart, and muscles.
- ALT (Alanine Aminotransferase): Found mainly in the liver; more specific for hepatic injury.
Reference Values:
- AST: 6 – 25 U/L
- ALT: 3 – 30 U/L
Clinical Significance:
- Marked Increase (up to 100× ULN): Severe hepatic cell injury such as viral hepatitis, toxic hepatitis, or chemical poisoning (e.g., chloroform, carbon tetrachloride).
- Moderate Increase: Cirrhosis, chronic hepatitis, cholestasis, or liver tumors.
- AST:ALT Ratio:
- Ratio >2 indicates alcoholic liver disease.
- Ratio <1 suggests viral hepatitis.
ALT is more liver-specific, while AST may also increase in muscle injury or myocardial infarction.
3. γ-Glutamyl Transferase (GGT)
Gamma Glutamyl Transferase (GGT) is an enzyme that transfers the γ-glutamyl group from peptides to amino acids or water. It is highly concentrated in the liver, kidney, and pancreas and serves as a sensitive marker of liver injury.
Reference Values:
- Males: 3 – 35 U/L
- Females: 3 – 30 U/L
Clinical Significance:
- Increased GGT: Seen in hepatocellular and obstructive liver diseases.
- Not elevated in bone diseases (unlike ALP), making it more specific for liver injury.
Diagnostic Uses:
- Alcohol-induced liver injury: GGT is the enzyme of choice for detecting alcoholism-related hepatic damage.
- Hepatic metastasis: GGT often rises before jaundice develops.
- Monitoring hepatitis: A return of GGT to normal indicates recovery, while a secondary rise indicates relapse.
- Chronic bile duct obstruction: Helps differentiate liver disease from bone disorders.
4. 5’-Nucleotidase (NTP)
5’-Nucleotidase (NTP) hydrolyzes phosphate from adenosine mononucleotide (AMP). It is a microsomal enzyme found in the liver and other tissues but is particularly useful in distinguishing hepatic from bone-related ALP elevations.
Reference Values:
- Normal Range: 0.4 – 7.0 U/L
Clinical Significance:
- Increased NTP: Indicates hepatobiliary disease, particularly cholestasis and hepatic metastasis.
- Remains normal in bone disorders — useful for differentiating elevated ALP of liver origin.
- Useful in monitoring infectious hepatitis progression or relapse.
5. Ornithine Carbamoyl Transferase (OCT)
OCT is a mitochondrial enzyme involved in the urea cycle, catalyzing the transfer of a carbamoyl group from carbamoyl phosphate to ornithine. Since it is almost exclusively found in the liver, its rise in serum is highly specific for hepatic injury.
Reference Values:
- Normal Range: Up to 6 U/L
Clinical Significance:
- Highly specific for acute hepatic injury.
- Used to detect intermittent obstruction of the common bile duct.
- Not increased in non-hepatic tissue damage.
6. Isoenzymes
Some enzymes exist in multiple molecular forms called isoenzymes. Each isoenzyme form is associated with a specific tissue, and their separation helps identify the origin of tissue injury.
Examples:
- Alkaline Phosphatase Isoenzymes: Liver isoenzyme moves faster than the bone isoenzyme on electrophoresis, helping distinguish hepatic from bone disease.
- Lactate Dehydrogenase (LDH) Isoenzymes:
- LD5: Predominantly in liver.
- LD2: Found in heart and other tissues.
Summary Table: Common Enzyme Tests in Liver Diseases
| Enzyme | Normal Range (U/L) | Increased In | Clinical Significance |
|---|---|---|---|
| ALP | 20–105 | Cholestasis, bone disorders, liver tumors | Helps distinguish obstructive jaundice and bone disease |
| AST (GOT) | 6–25 | Hepatitis, myocardial infarction, muscle injury | Rises earlier in liver injury; not specific |
| ALT (GPT) | 3–30 | Viral hepatitis, hepatic necrosis | More specific for liver injury |
| GGT | 3–35 (M), 3–30 (F) | Liver disease, alcoholism, bile duct obstruction | Specific for hepatobiliary disorders; unaffected by bone disease |
| 5’-Nucleotidase | 0.4–7.0 | Cholestasis, liver metastasis | Differentiate hepatic vs bone causes of ALP rise |
| OCT | Up to 6 | Hepatic cell damage, bile duct obstruction | Highly specific for hepatic injury |
Detailed Notes:
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