What laboratory tests are typically abnormal in patients with liver cancer?

Laboratory Abnormalities in Liver Cancer

In patients with liver cancer (hepatocellular carcinoma), approximately 90% will have abnormal alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and albumin levels, making these the most consistently abnormal laboratory tests. 1

Primary Laboratory Abnormalities

Hepatocellular Injury Markers

• ALT and AST elevations occur in approximately 90% of hepatocellular carcinoma patients, though the degree of elevation varies widely 1
• The pattern is typically hepatocellular (ALT/AST predominant) rather than cholestatic, though mixed patterns can occur 2
• ALT is more liver-specific than AST, as AST can be elevated from cardiac muscle, skeletal muscle, kidney, or red blood cell disorders 2, 3
• In oncology patients with liver metastases, baseline ALT >1× ULN occurs in 31% of cases, though ALT ≥3× ULN occurs in <5% 2

Cholestatic Markers

• Alkaline phosphatase (ALP) elevation is present in approximately 90% of HCC cases 1
• ALP elevation ranges from 37.2% in patients without detectable hepatic metastases to 67% in patients with hepatic metastases 2
• Raised ALP in the presence of normal bilirubin is more often a feature of HCC than benign liver disease, though this relationship is not always statistically significant 1
• Gamma-glutamyltransferase (GGT) is abnormal in approximately 90% of HCC cases 1

Synthetic Function Markers

• Albumin is abnormal in approximately 90% of hepatocellular carcinoma patients 1
• Bilirubin elevations are less frequent than aminotransferase elevations in liver cancer 2
• In patients with liver metastases, the prevalence of total bilirubin >1× ULN is only 5%, and exceeding 2× ULN occurs in just 0.6% of cases 2
• Prothrombin time/INR may be prolonged, reflecting impaired hepatic synthetic function 2

Tumor-Specific Markers

Alpha-Fetoprotein (AFP)

• AFP levels >200 ng/mL have a positive predictive value >90% for hepatocellular carcinoma 4
• Persistently elevated AFP levels in the setting of focal hepatic lesions have high diagnostic value 4
• Other less commonly measured biomarkers include glycosylated AFP-L3 and des-gamma-carboxy prothrombin (vitamin K-deficiency induced) 4

Additional Laboratory Findings

Hematologic Abnormalities

• Quickly deteriorating blood counts may indicate illness progression 4
• Haemostatic disorders can occur in severe cases 4

Metabolic Derangements

• Hypoglycemia may occur occasionally in advanced disease 4
• Hypercalcemia can develop in some cases 4

Important Clinical Considerations

Distinguishing Primary vs. Metastatic Disease

• The type of primary tumor influences baseline biochemistry based on propensity to spread to the liver 2
• Colorectal cancer metastatic to the liver shows baseline ALT >3× ULN in 30% of patients, compared to only 4% in chronic lymphocytic leukemia 2
• Liver metastases are more common in colorectal adenocarcinoma (14%) and malignant melanoma (13%) compared to lung (8%) and breast adenocarcinomas (6%) 2

Diagnostic Limitations

• With the exception of bilirubin, liver function tests are abnormal more frequently in HCC than in chronic hepatitis and cirrhosis (the conditions which precede it) 1
• However, liver function tests alone have limited utility for definitively diagnosing HCC, as they lack specificity 1
• Normal liver function tests do not exclude significant liver disease, as up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds 3

Competing Causes to Consider

• Patients with malignant tumors may have elevated liver enzymes due to hepatic metastases, biliary obstruction, hepatic vein thrombosis, congestive heart failure, or systemic infections 2
• Drug-induced liver injury from chemotherapy or other medications must be differentiated from tumor-related changes 2, 5
• Viral hepatitis B, C, and Delta, metabolic disorders, and non-alcoholic steatohepatitis should be evaluated to clarify etiology 4