Comprehensive Liver Function Evaluation
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, 2
Initial Laboratory Evaluation
Core Laboratory Tests
- Serum aminotransferases (AST and ALT) - indicate hepatocellular injury and necrosis, with ALT being more specific for liver injury 2, 1
- Alkaline phosphatase (ALP) - elevated in cholestatic liver disease 2, 1
- Bilirubin (total and direct) - elevated in various hepatobiliary disorders 1, 3
- Albumin - reflects the liver's synthetic capacity 2, 1
- Prothrombin time/INR - measures clotting factors synthesized by the liver 2, 1
- Platelet count - low count may suggest portal hypertension in advanced liver disease 2, 1
- Gamma-glutamyl transpeptidase (GGT) - can help confirm hepatic origin of ALP elevation 4
Pattern Recognition
- Hepatocellular pattern: Predominant elevation of aminotransferases (AST, ALT) 2, 3
- Cholestatic pattern: Predominant elevation of alkaline phosphatase and/or bilirubin 2, 3
- Mixed pattern: Elevations in both aminotransferases and alkaline phosphatase 3, 5
Secondary Evaluation Based on Initial Findings
For Hepatocellular Pattern (Elevated Aminotransferases)
- Mild: <5 times upper limit of normal
- Moderate: 5-10 times upper limit of normal
- Severe: >10 times upper limit of normal
Additional testing should include 1, 3:
- Viral hepatitis panel (HBsAg, hepatitis B surface antibody, HBcAb, HCV antibodies)
- Autoimmune markers (ANA, ASMA, ANCA)
- Iron studies (ferritin, transferrin saturation)
- Ceruloplasmin (for Wilson's disease)
- α1-antitrypsin levels
- Alcohol use assessment
For Cholestatic Pattern (Elevated Alkaline Phosphatase)
- Additional testing should include 2, 3:
- GGT to confirm hepatic origin of ALP elevation
- Antimitochondrial antibodies (for primary biliary cholangitis)
- Imaging studies (ultrasound, CT, or MRI)
- MRCP or ERCP if biliary obstruction is suspected
Advanced Assessment of Liver Function
Non-invasive Fibrosis Assessment
- FIB-4 (uses age, AST, ALT, platelet count)
- NAFLD Fibrosis Score (for non-alcoholic fatty liver disease)
- Transient elastography (FibroScan®)
- MR elastography
Liver Synthetic Function Assessment
- Child-Pugh classification - incorporates laboratory measurements (albumin, bilirubin, prothrombin time) and clinical assessments (encephalopathy, ascites) 2, 1
- MELD score - uses bilirubin, creatinine, and INR 2, 1
- Albumin-Bilirubin (ALBI) grade - considers serum albumin and bilirubin levels 2, 1
Imaging Studies in Liver Function Assessment
- Ultrasound - first-line imaging modality for liver assessment; can detect fatty infiltration, cirrhosis, and biliary dilatation 2, 6
- CT scan - useful for evaluating liver masses and vascular structures 2
- MRI/MRCP - superior for characterizing focal lesions and evaluating biliary anatomy 2
- Elastography - quantifies liver stiffness as a surrogate for fibrosis 2, 1
Liver Biopsy Considerations
- Consider liver biopsy when 3, 6:
- Serologic testing and imaging fail to establish a diagnosis
- Staging of known liver disease is needed
- Multiple diagnoses are possible
- Unexplained persistent elevation of liver enzymes
Common Pitfalls in Liver Function Evaluation
- Normal values do not exclude liver disease - 2.5% of healthy individuals may have abnormal elevation of a given liver chemistry test 1
- The AST/ALT ratio can be misleading - while a ratio >2 suggests alcoholic liver disease, exceptions exist 1
- Isolated ALP elevation may be of non-hepatic origin (bone disease) - confirm with GGT 2, 4
- Medications can cause abnormal liver tests - always obtain a complete medication history 2, 3
- Spectrum effect - non-invasive tests may perform differently in populations with different disease prevalence 2
Monitoring Recommendations
- Frequency of monitoring depends on the underlying condition and severity 2
- For mild abnormalities without identified cause, repeat testing in 2-3 months 3
- For patients on hepatotoxic medications, monitor according to medication-specific guidelines 7, 2
- For chronic liver diseases, monitoring intervals should be determined based on disease activity and treatment status 2