Elevated Liver Function Tests (LFT’s)


Specific Liver Function Tests (LFT’s) (see Liver Function Tests)

Transaminases (Aminotransferases) (see Serum Transaminases)

  • Transaminases (Aminotransferases)
    • Aspartate Aminotransferase (AST) (see Serum Transaminases)
      • Formerly Called Serum Glutamate-Oxaloacetate Transaminase (SGOT)
    • Alanine Aminotransferase (ALT) (see Serum Transaminases)
      • Formerly Called Serum Glutamate-Pyruvate Transaminase (SGPT)
  • Origin of Transaminases (Aminotransferases)
    • Liver: AST and ALT
    • Cardiac and Skeletal Muscle: AST only
    • Thyroid: AST only
  • Sensitivity/Specificity of Transaminases (Especially ALT) for the Differentiation of Liver Disease from Other Disorders Depends on the Cutoff Value Chosen to Define an Abnormal Result
    • ALT Levels Correlate with the Degree of Abdominal Adiposity Vary Between the Sexes
    • AST and ALT Upper Limits of Normal Vary Between Laboratories: due to differing reference standards used
    • Optimal ALT Cutoff Value (Male): 29 IU/L (Hepatology, 2012) [MEDLINE]
    • Optimal ALT Cutoff Value (Female): 22 IU/L (Hepatology, 2012) [MEDLINE]

Alkaline Phosphatase (see Serum Alkaline Phosphatase)

  • Origin of Alkaline Phosphatase
    • Bone
    • Intestine
    • Kidney
    • Liver
    • Third Trimester Placenta
  • Determination of Origin
    • Elevated Alkaline Phosphatase Associated with a Normal Gamma-Glutamyl Transpeptidase or 5′-Nucleotidase Suggests a Non-Hepatic Source of the Alkaline Phosphatase
    • Fractionation of Alkaline Phosphatase: may also be used to determine origin
      • Heat-Labile Alkaline Phosphatase: suggests bone origin (“bone burns”)
      • Heat-Stable Alkaline Phosphatase: suggests liver origin
  • Alkaline Phosphatase Levels are Age-Dependent
    • Alkaline Phosphatase Levels are Higher (Up to 3x Adult Levels) in Children and Adolescents: due to physiologic osteoblastic activity
    • Normal Alkaline Phosphatase Level Increases from 40 to 65 y/o: especially in women

Gamma-Glutamyl Transpeptidase (GGT) (see Serum Gamma-Glutamyl Transpeptidase)

  • General Comments
    • Gamma-Glutamyl Transpeptidase is Elevated in Normal Neonates: levels decrease and reach adult levels by 5-7 mo of age
    • Although GGT Has High Sensitivity for Liver Disease, Due to its Low Specificity, it Should Only Be Used to Evaluate Other LFT Abnormalities
  • Origin of Gamma-Glutamyl Transpeptidase
    • Biliary Epithelial Cells
    • Brain
    • Heart
    • Hepatocytes
    • Kidney
    • Pancreas
    • Seminal Vesicle
    • Spleen

Bilirubin (see Serum Bilirubin)

5′-Nucleotidase (see Serum 5′-Nucleotidase)

  • General Comments
    • Physiologic Function of 5′-Nucleotidase is Unknown
  • Origin of 5′-Nucleotidase
    • Blood Vessels
    • Brain
    • Endocrine Pancreas
    • Heart
    • Liver: liver is the only organ which releases 5′-nucleotidase into the serum

Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase)

  • General Comments
    • LDH is a Cytoplasmic Enzyme Found in Many Organs
    • There are 5 LDH Isoenzymes of LDH Present in the Serum: isoenzymes can be separated by electrophoresis
    • Slowest Migrating Isoenzyme is the Predominant Form Present in the Liver
  • Origin of Lactate Dehydrogenase Isoenzymes
    • LDH-1 (4H) Isoenzyme
      • Brain
      • Heart
      • Red Blood Cell (RBC)
    • LDH-2 (3H1M) Isoenzyme
      • Reticuloendothelial System
    • LDH-3 (2H2M) Isoenzyme
      • Lung
    • LDH-4 (1H3M) Isoenzyme
      • Kidney
      • Pancreas
      • Placenta
    • LDH-5 (4M) Isoenzyme
      • Liver
      • Striated Muscle

Patterns of Liver Function Test Abnormalities

General Patterns

Magnitude of AST and ALT Elevation


Etiology of Mildly-Moderately Elevated Transaminases (Transaminitis <15x Upper Limit of Normal)

Hepatic Disease

AST-Predominant (AST/ALT Ratio ≥1)

ALT-Predominant (AST/ALT Ratio <1)

Non-Hepatic Disease

Clinical Evaluation of Mildly-Moderately Elevated Transaminases (Transaminitis <15x Upper Limit of Normal)


Etiology of Markedly Elevated Transaminases (Transaminitis >15x Upper Limit of Normal)

Fulminant Hepatic Failure (Acute Liver Failure) (see Fulminant Hepatic Failure)

Other Liver Disease (without Fulminant Hepatic Failure)

Other Disorders

Clinical Evaluation of Markedly Elevated Transaminases (Transaminitis >15x Upper Limit of Normal)


Etiology of Moderately Elevated Alkaline Phosphatase Elevation (<4x Upper Limit of Normal) (see Serum Alkaline Phosphatase)

Hepatic

Non-Hepatic

Clinical Evaluation of Elevated Alkaline Phosphatase (of Hepatic Origin) (see Serum Alkaline Phosphatase)


Etiology of Markedly Elevated Alkaline Phosphatase Elevation (≥4x Upper Limit of Normal) (see Serum Alkaline Phosphatase)

Intrahepatic Cholestasis

Extrahepatic Cholestasis (Biliary Obstruction)

Non-Hepatic

Clinical Evaluation of Elevated Alkaline Phosphatase (of Hepatic Origin) (see Serum Alkaline Phosphatase)


Etiology of Isolated Gamma-Glutamyl Transpeptidase Elevation (see Serum Gamma-Glutamyl Transpeptidase)


Etiology of Isolated Hyperbilirubinemia (see Hyperbilirubinemia)

Unconjugated (Indirect) Hyperbilirubinemia

Increased Bilirubin Production

Impaired Hepatic Bilirubin Uptake

Impaired Bilirubin Conjugation

Conjugated (Direct) Hyperbilirubinemia

Inherited Disorders

Intrahepatic Cholestasis

Extrahepatic Cholestasis (Biliary Obstruction)


References