How to evaluate liver function?

Evaluation of Liver Function

The initial assessment of liver function should include a comprehensive panel of liver chemistry tests including serum levels of bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), prothrombin time expressed as international normalized ratio (INR), albumin, and platelet count. 1

Initial Laboratory Evaluation

Hepatocellular Markers

• Aminotransferases (AST and ALT): Elevated levels indicate hepatocyte injury and necrosis. ALT elevations are more specific for liver injury due to low concentrations in other tissues 1
• Severity classification of aminotransferase elevation:
  • Mild: <5 times the upper reference limit
  • Moderate: 5-10 times the upper reference limit
  • Severe: >10 times the upper reference limit 1
• AST/ALT ratio: Can help distinguish alcoholic liver disease (ratio >2) from non-alcoholic fatty liver disease 1

Cholestatic Markers

• Alkaline Phosphatase (ALP): Elevated in cholestatic liver disease, which can occur with or without elevated bilirubin 1
• Gamma-Glutamyl Transpeptidase (GGT): Should be measured to confirm hepatic origin of ALP elevation 2

Synthetic Function Markers

• Albumin: Reflects the liver's synthetic capacity; decreased levels suggest chronic liver disease 1
• Prothrombin Time/INR: Measures clotting factors synthesized by the liver; prolongation indicates impaired synthetic function 1

Other Essential Tests

• Bilirubin (Total and Direct/Conjugated): Elevated levels may indicate various hepatobiliary disorders 1
• Platelet Count: Surrogate marker for portal hypertension; thrombocytopenia may suggest advanced liver disease 1
• Complete Blood Count: Important for assessing overall health status and potential complications 1
• Blood Urea Nitrogen and Creatinine: To assess kidney function, which is often affected in liver disease 1

Diagnostic Approach Based on Pattern of Abnormalities

Hepatocellular Pattern (Predominant Aminotransferase Elevation)

1. Initial evaluation:

   • Exclude common hepatic diseases with noninvasive serologic tests 1
   • Hepatitis panel (HBsAg, hepatitis B surface antibody, HBcAb, HCV antibodies) 1
   • Confirm viral load in patients who test positive for viral markers 1

2. Further evaluation for persistent or significant elevations:

   • Additional serologic testing for autoimmune markers, iron studies, α1-antitrypsin, ceruloplasmin 1
   • Imaging studies (ultrasound, CT, or MRI depending on clinical scenario) 1
   • Consider liver biopsy for chronic elevations (≥6 months) without clear etiology 1

Cholestatic Pattern (Predominant ALP Elevation)

1. Initial evaluation:

   • Confirm hepatic origin of ALP elevation by measuring GGT 2
   • Abdominal ultrasound to evaluate biliary system and exclude obstruction 2

2. Further evaluation:

   • If extrahepatic obstruction is suspected: Consider MRCP, ERCP, or EUS 1
   • If intrahepatic cholestasis is suspected: Evaluate for primary biliary cholangitis, primary sclerosing cholangitis, drug-induced liver injury 2

Hyperbilirubinemia

1. Determine if unconjugated (indirect) or conjugated (direct):
   • Unconjugated: Evaluate for hemolysis, Gilbert's syndrome, ineffective erythropoiesis 1, 2
   • Conjugated: Evaluate for biliary obstruction, hepatocellular disease, or rare genetic disorders like Dubin-Johnson or Rotor syndromes 1, 2

Advanced Assessment of Liver Function

Non-invasive Assessment of Fibrosis

• Simple fibrosis scores (FIB-4, NAFLD Fibrosis Score): Useful for initial risk stratification 1
• Elastography techniques (FibroScan®, MR elastography): Can quantify degree of fibrosis 1

Liver Function Classification Systems

• Child-Pugh classification: Incorporates laboratory measurements (albumin, bilirubin, prothrombin time) and clinical assessments (encephalopathy, ascites) 1
• MELD score: Uses bilirubin, creatinine, and INR; originally developed for TIPS procedures, now used for liver transplant allocation 1
• Albumin-Bilirubin (ALBI) grade: Considers serum albumin and bilirubin levels; helpful in predicting survival outcomes 1

Common Pitfalls in Liver Function Evaluation

• Normal values do not exclude liver disease: By definition, 2.5% of healthy individuals will have abnormal elevation of a given liver chemistry test 1
• Isolated abnormalities may not indicate liver disease: Many markers are not specific for the liver and can be affected by factors unrelated to liver disease 3
• Liver enzymes measure injury, not function: Tests like AST and ALT indicate liver injury but do not directly measure liver function 3
• Spectrum effect: Non-invasive tests should be applied to populations with risk factors for liver disease rather than unselected populations to minimize false positives 1
• Temporary events may affect assessment: Renal failure, spontaneous bacterial peritonitis, hyponatremia, recurrent encephalopathy, or malnutrition may indicate end-stage liver disease requiring transplant 1

Comprehensive Evaluation Algorithm

1. Initial liver chemistry panel: AST, ALT, ALP, GGT, bilirubin (total and direct), albumin, INR, platelet count 1
2. Determine pattern of abnormality: Hepatocellular, cholestatic, or mixed 1
3. Assess severity: Mild, moderate, or severe elevations; evidence of synthetic dysfunction 1
4. Targeted evaluation based on pattern and severity:
   • Viral hepatitis serology
   • Autoimmune markers
   • Iron studies
   • Abdominal imaging
   • Non-invasive fibrosis assessment 1
5. Consider liver biopsy for persistent unexplained abnormalities or suspected advanced disease 1
6. Assess hepatic functional reserve using Child-Pugh, MELD, or ALBI scores in patients with evidence of chronic liver disease 1