What baseline and follow‑up laboratory tests should be ordered for a patient with suspected or known chronic liver disease?

Laboratory Parameters in Chronic Liver Disease

Initial Core Laboratory Panel

All patients with suspected or known chronic liver disease should undergo a standardized initial laboratory assessment including bilirubin, albumin, ALT, alkaline phosphatase (ALP), and GGT, together with a complete blood count if not performed within the previous 12 months 1. This core panel provides essential information about hepatocellular injury, cholestasis, synthetic function, and portal hypertension risk 1.

Baseline Tests for All Patients

• Hepatocellular injury markers: ALT and AST serve as primary indicators of liver cell damage 1, 2
• Cholestatic markers: ALP and GGT detect biliary obstruction and cholestatic disease 1, 2
• Synthetic function: Albumin reflects hepatic synthetic capacity and disease chronicity 1, 2
• Excretory function: Total and direct bilirubin assess hepatic excretory capacity 1, 2
• Coagulation status: Prothrombin time/INR evaluates synthetic function and coagulation 1, 2
• Portal hypertension surrogate: Platelet count serves as a marker for advanced fibrosis and portal hypertension 1, 2

Standard Etiologic Screen (Core Panel)

Once abnormal liver tests are identified, a comprehensive etiologic workup must be performed regardless of the degree or duration of abnormality 1. The standard liver aetiology screen should include 1:

Viral Hepatitis Serologies

• Hepatitis B surface antigen (HBsAg) to detect active HBV infection 1, 2
• Hepatitis C antibody with reflex PCR if positive to confirm active HCV 1, 2
• For marked elevations (ALT >1000 U/L): Add hepatitis A IgM, hepatitis E IgM, and cytomegalovirus serologies 1, 3

Autoimmune Markers

• Anti-mitochondrial antibody (AMA) for primary biliary cholangitis 1, 2
• Anti-smooth muscle antibody (ASMA) for autoimmune hepatitis 1, 2
• Antinuclear antibody (ANA) for autoimmune conditions 1, 2
• Serum immunoglobulins (elevated IgG suggests autoimmune hepatitis) 1, 2

Metabolic Screening

• Simultaneous serum ferritin and transferrin saturation to evaluate for hemochromatosis (transferrin saturation >45% is significant) 1, 2
• Fasting glucose or HbA1c for metabolic dysfunction-associated steatotic liver disease (MASLD) 2
• Lipid panel for MASLD evaluation 2

Imaging

• Abdominal ultrasound is mandatory as part of the initial workup to assess liver architecture, detect steatosis, identify masses, and evaluate for biliary obstruction 1, 2

Non-Invasive Fibrosis Assessment

Patients with confirmed chronic liver disease require fibrosis staging using non-invasive tests to identify those with compensated advanced chronic liver disease (cACLD) 1.

First-Line Fibrosis Scores

• FIB-4 score ≥1.30 (or ≥1.75 for higher specificity) identifies patients who may benefit from liver stiffness measurement 1
• FIB-4 ≥1.75 corresponds to liver stiffness ≥10 kPa and identifies patients at risk for hepatic decompensation 4
• NAFLD Fibrosis Score (NFS) can be used as an alternative first-line test 1

Second-Line Assessment

• Transient elastography (FibroScan): LSM ≥10 kPa suggests cACLD; ≥15 kPa is highly suggestive of cACLD 1
• LSM 10-15 kPa with platelet count >150,000/μL helps rule out cACLD 1
• LSM ≥8 kPa with FIB-4 ≥1.30 warrants hepatology referral 1

Follow-Up Laboratory Monitoring

For Patients with cACLD

Patients with established cACLD require laboratory monitoring every 6-12 months 1:

• Platelet count as a surrogate for clinically significant portal hypertension (CSPH) 1
• Bilirubin and albumin as surrogates for hepatic function 1
• AST and ALT to monitor disease activity 1
• GGT and ALP for cholestatic component 1

Advanced Risk Stratification

• Von Willebrand factor/platelet ratio (VITRO) <1.0 rules out CSPH with 100% sensitivity 4
• VITRO ≥2.5 rules in CSPH with 92.4% specificity 4
• Post-SVR patients with LSM <12 kPa and platelets >150,000/μL do not need endoscopy for varices 1

Hepatocellular Carcinoma Surveillance

Patients with cACLD, previous portal hypertension complications, or HCC history require ongoing surveillance even after successful etiologic therapy 1:

• Alpha-fetoprotein (AFP) every 6 months, though it has limited specificity 2
• Abdominal ultrasound every 6 months for HCC screening 1

Critical Pitfalls to Avoid

• Do not simply repeat abnormal liver tests without investigating the underlying cause: 84% of abnormal tests remain abnormal at 1 month, and 75% remain abnormal at 2 years without intervention 5
• Isolated elevated ferritin does not indicate hemochromatosis: It is commonly elevated in dysmetabolic iron overload syndrome, alcohol excess, NAFLD, and other chronic liver diseases 1
• Country of origin (not ethnic group) is the strongest predictor of viral hepatitis: Tailor screening accordingly 1
• In patients with metabolic risk factors never exposed to HBV/HCV: Use FIB-4 ≥1.30 as the first diagnostic tool before proceeding to liver stiffness measurement 1

Referral Criteria

Immediate hepatology referral is indicated for 1, 2:

• Positive HBsAg or HCV antibody with detectable viral load
• Positive AMA (primary biliary cholangitis)
• Elevated IgG with positive autoantibodies (autoimmune hepatitis)
• Transferrin saturation >45% with elevated ferritin (hemochromatosis)
• FIB-4 and LSM suggesting cACLD (FIB-4 ≥1.30 with LSM ≥8 kPa)
• Evidence of hepatic decompensation (thrombocytopenia, AST>ALT ratio, hypoalbuminemia, elevated INR)
• Dilated bile ducts on imaging