Chemistry, toxicology & urinalysis

• Liver function tests (LFTs)
• Hepatic function panel
• Liver profile

• Alanine aminotransferase (ALT)
  • Synonym
    • Serum glutamic pyruvic transaminase (SGPT)
  • Indications
    • Diagnosis and monitoring of liver disease associated with hepatic necrosis
  • Test methodology
    • Photometric rate, L-alanine with pyridoxal-5-phosphate
  • Example of reference ranges:
    • Males
      • ≥ 1 year: 7 - 55 U/L
      • Not established for patients < 12 months of age
    • Females
      • ≥ 1 year: 7 - 45 U/L
      • Not established for patients < 12 months of age
  • Interpretation
    • Present primarily in liver cells and elevated even prior to clinical signs and symptoms appearing in viral hepatitis and other liver diseases with hepatic necrosis
    • A more liver specific enzyme than aspartate aminotransferase (AST), even though both are elevated in liver disease; however, the elevation of ALT activity persists longer than AST
    • Elevated values seen in parenchymal liver diseases with destruction of hepatocytes; 20 - 50 times elevations are mostly seen and may reach as high as 100 times the upper limit
    • ALT is as high as or higher than AST in infections and inflammatory conditions of the liver; the ALT:AST ratio, normally less than 1, becomes greater than 1
    • Elevated ALT levels persist longer than AST
  • Preanalytic considerations
    • Pyridoxal phosphate is a cofactor in the reaction and is required for enzyme activity

• Aspartate aminotransferase (AST)
  • Synonym
    • Serum glutamic oxaloacetic transaminase (SGOT)
  • Indications
    • Diagnosing and monitoring of liver disease that results in destruction of hepatocytes
  • Test methodology
    • Photometric rate, L-aspartate with pyridoxyl-5-phosphate
  • Example of reference ranges:
    • Males
      • 0 - 11 months: not established
      • 1 - 13 years: 8 - 60 U/L
      • ≥ 14 years: 8 - 48 U/L
    • Females
      • 0 - 11 months: not established
      • 1 - 13 years: 8 - 50 U/L
      • ≥ 14 years: 8 - 43 U/L
  • Interpretation
    • Elevated in alcoholism, cirrhosis, hepatitis, drug therapy and biliary disease
    • Depressed in uremia, B6 deficiency and drug therapy
    • Typically lower than ALT in infections and inflammatory conditions of the liver; the ALT:AST ratio, normally less than 1, becomes greater than 1
    • Elevated before clinical signs and symptoms of disease appear
    • In primary or metastatic carcinoma of the liver, 5 - 10 times elevations of both AST and ALT occur, with AST being higher than ALT but levels are usually normal in early malignancy
    • Elevations more short lived than ALT
    • May also be elevated in disorders of the heart, skeletal muscle and kidney
  • Preanalytic considerations
    • Pyridoxal phosphate is a cofactor in the reaction and is required for enzyme activity

• Alkaline phosphatase (ALP)
  • Indications
    • Diagnosing and monitoring treatment of liver, bone, intestinal and parathyroid diseases
  • Test methodology
    • Colorimetric
  • Example of reference ranges:
    • Males
      • 0 - 14 days: 83 - 248 U/L
      • 15 days - < 1 year: 122 - 469 U/L
      • 1 - < 10 years: 142 - 335 U/L
      • 10 - < 13 years: 129 - 417 U/L
      • 13 - < 15 years: 116 - 468 U/L
      • 15 - < 17 years: 82 - 331 U/L
      • 17 - < 19 years: 55 - 149 U/L
      • ≥ 19 years: 40 - 129 U/L
    • Females
      • 0 - 14 days: 83 - 248 U/L
      • 15 days - < 1 year: 122 - 469 U/L
      • 1 - < 10 years: 142 - 335 U/L
      • 10 - < 13 years: 129 - 417 U/L
      • 13 - < 15 years: 57 - 254 U/L
      • 15 - < 17 years: 50 - 117 U/L
      • ≥ 17 years: 35 - 104 U/L
  • Interpretation
    • Increase in ALP greater than 4 times the upper reference value is seen in extrahepatic obstruction, for example by stones or cancer of the head of the pancreas
    • Greater than 4 times the upper reference value increase is seen in advanced primary liver cancer or widespread hepatic metastases
    • Greater than 2 times the upper reference value can predict transplant free survival rates of patients with primary biliary cholangitis
    • Normal to moderately increased (less than 3 times) in hepatic parenchymal diseases, e.g. infectious hepatitis
    • Reaction to drug therapy may also lead to elevated ALP levels; an ALT / ALP based criterion can be used to distinguish the type of liver injury in drug induced hepatic toxicity
    • Liver cirrhosis also causes elevations in intestinal ALP isoenzyme as it is an asialoglycoprotein that is cleared by the hepatic asialoglycoprotein receptors
    • Hepatic versus bone elevations can be distinguished by isoenzyme electrophoresis
  • Postanalytic considerations
    • Age specific reference values should be used as values are higher in children and adolescents with bone growth

• Albumin
  • Indications
    • Diagnosis and monitoring of nutritional diseases, liver function and renal function
  • Test methodology
    • Photometric, bromocresol green
  • Example of reference ranges:
    • ≥ 12 months: 3.5 - 5.0 g/dL
    • Not established for patients < 12 months of age
  • Interpretation
    • Hyperalbuminemia occurs in dehydration
    • Hypoalbuminemia (below 2.0 g/dL) occurs in edema
    • Decreased serum albumin levels can be seen with reduced intake in malnutrition; increased turnover associated with glucocorticoid use and excessive loss in protein losing enteropathy, nephrotic syndrome or burn injury
  • Postanalytic considerations
    • Albumin values measured by the bromocresol green method may be different from those measured by electrophoresis

• Total protein (TP)
  • Indications
    • Diagnosis of diseases involving the liver, kidneys, bone marrow and other metabolic or nutritional disorders
  • Test methodology
    • Colorimetric, biuret
  • Example of reference range:
    • ≥ 1 year: 6.3 - 7.9 g/dL
    • Not established for patients < 12 months of age
  • Interpretation
    • Inflammation, infection and late stage liver disease cause increase in acute phase reactants and polyclonal immunoglobulins, leading to mild hyperproteinemia
    • Multiple myeloma and other malignant paraproteinemias often cause moderate to marked hyperproteinemia
    • Hypogammaglobulinemia, nephrotic syndrome and protein losing enteropathy lead to hypoproteinemia
  • Preanalytic considerations
    • If the patient is in the recumbent position at the time of collection, total protein concentration is characteristically 0.4 - 0.8 mg/dL lower

• Total bilirubin
  • Synonym
    • Neonatal bilirubin
  • Indications
    • Diagnosis of liver, hemolytic, hematologic and metabolic disorders, including hepatitis and gallbladder obstructive disease
    • Monitoring the efficacy of neonatal phototherapy
  • Test methodology
    • Photometric, diazonium salt (DPD)
  • Example of reference ranges:
    • 0 - 6 days: refer to BiliTool for information on age specific (postnatal hour of life) serum bilirubin values
    • 7 - 14 days: < 15.0 mg/dL
    • 15 days - 17 years: ≤ 1.0 mg/dL
    • ≥ 18 years: ≤ 1.2 mg/ dL
    • Critical values above 16.0 mg/dL only for patients under the age of 1
  • Interpretation
    • Sum of direct bilirubin (associated with liver) and indirect bilirubin (bound to albumin in circulation)
    • Less than 20 mg/dL of total serum bilirubin (TSB) typically poses no risk of kernicterus (central nervous system damage caused by hyperbilirubinemia); however, premature infants may be affected at lower levels
    • TSB guides decision to start phototherapy
    • Phototherapy is stopped when TSB reaches 14 - 15 mg/dL
  • Preanalytic considerations
    • Ship specimen in amber vial or wrapped in aluminum foil to protect from light which causes photoisomerization of bilirubin in samples and falsely increases measured direct bilirubin
    • Hemolyzed specimens should be rejected as hemoglobin interferes with the diazo reaction, resulting in falsely low levels
    • Compounds, e.g. penicillin, sulfisoxazole and acetylsalicylic acid, compete for binding sites on serum albumin and lead to lower serum bilirubin levels

• Direct bilirubin
  • Synonym
    • Bilirubin, conjugated
  • Indications
    • Used in the diagnosis and treatment of liver, hemolytic, hematologic and metabolic disorders, including hepatitis and gallbladder obstruction
  • Test methodology
    • Photometric, diazotized sulfanilic acid
  • Example of reference ranges:
    • < 31 days: 0 - 0.6 mg/dL
    • ≥ 31 days: 0 - 0.3 mg/dL
  • Interpretation
    • Both direct and indirect bilirubin are increased in hepatic diseases, such as hepatitis and tumors or obstructive lesions, such as carcinomas of the pancreas, common bile duct and ampulla of Vater
    • Should be assessed in conjunction with total and indirect levels and the clinical setting
  • Preanalytic considerations
    • Ship specimen in amber vial or wrapped in aluminum foil to protect from light which can cause falsely elevated values (see discussion above for total bilirubin)
    • Hemolyzed specimens should be rejected as hemoglobin interferes with the diazo reaction, resulting in falsely low levels
• Reference: Med Clin North Am 2014;98:1

• Postgrad Med J 2000;76:129, Curr Opin Crit Care 2010;16:136, Clin Lab Med 2002;22:377, Clin Liver Dis 2009;13:167

Which of the following is true about AST and ALT?

1. ALT levels help to guide neonatal phototherapy
2. ALT:AST ratio is normally greater than 1
3. AST levels may also be elevated in disorders of the heart, skeletal muscle and kidney
4. AST levels persist longer than ALT levels

C. AST levels may also be elevated in disorders of the heart, skeletal muscle and kidney. Since AST is widely expressed in tissues other than the liver, it is less specific for liver disease.

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Reference: Liver function test panel

Which of the following is true regarding serum alkaline phosphatase (ALP) levels?

1. Markedly increased in hepatic parenchymal diseases, such as infectious hepatitis
2. Measured using the photometric, diazonium salt method
3. Measured using the same reference values for children, adolescents and adults
4. Used in the diagnosis of liver, bone, intestinal and parathyroid diseases

D. Used in the diagnosis of liver, bone, intestinal and parathyroid diseases. ALP can be normal to moderately increased (less than 3 times) in hepatic parenchymal diseases, such as infectious hepatitis. Serum ALP level is measured using the colorimetric method. There should be separate reference values for children and adolescents than adults due to bone growth in the pediatric population.

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Reference: Liver function test panel