Laboratory Evaluation of Cirrhosis
Core Initial Laboratory Panel
All patients being evaluated for cirrhosis should undergo a comprehensive hepatic function panel including bilirubin, AST, ALT, alkaline phosphatase, albumin, PT/INR, platelet count, complete blood count, and renal function tests (BUN and creatinine). 1
Essential Baseline Tests
- Bilirubin (total and conjugated): Elevated conjugated bilirubin indicates advanced disease or biliary obstruction; critical for Child-Pugh and MELD scoring 2, 1
- AST and ALT: Typically elevated in active liver injury, with AST/ALT ratio often >1 in cirrhosis 2, 1
- Alkaline phosphatase: May be elevated, particularly in cholestatic liver disease 2, 1
- GGT: Useful for detecting hepatobiliary involvement and calculating fibrosis indices 2, 1
- Albumin: Decreased levels indicate impaired synthetic function and are essential for Child-Pugh scoring 2, 1
- PT/INR: Prolonged values reflect impaired hepatic synthetic function and are critical for both Child-Pugh and MELD scoring 2, 1
- Platelet count: Thrombocytopenia suggests portal hypertension and is a surrogate marker for advanced disease; also used to calculate APRI and FIB-4 scores 2, 1
- Creatinine and BUN: Essential for MELD score calculation and detecting hepatorenal syndrome; creatinine is an established prognostic marker 2, 1
Etiologic Workup
Once cirrhosis is suspected, determine the underlying cause through targeted serologic testing. 2, 1
Mandatory Screening Tests
- Hepatitis B panel: HBsAg, hepatitis B surface antibody, HBcAb, HBcAb IgM (only in acute hepatitis) 2, 1
- Hepatitis C antibody: Confirm viral load in all positive cases to guide antiviral therapy 2, 1
- Ferritin and transferrin saturation: Screen for hemochromatosis 2, 1
Additional Tests Based on Clinical Context
- Autoimmune markers: Consider if etiology remains unclear despite negative viral and metabolic workup 2, 1
- Alpha-1 antitrypsin level: Screen for alpha-1 antitrypsin deficiency 2, 1
- Ceruloplasmin: Consider for Wilson disease, particularly in younger patients 2, 1
Non-Invasive Fibrosis Assessment
Calculate fibrosis indices using readily available laboratory values to assess disease severity without biopsy. 1
- FIB-4 score: Uses age, AST, ALT, and platelet count 1
- APRI (AST to Platelet Ratio Index): Uses AST and platelet count 1
- GPR (GGT to Platelet Ratio): Uses GGT and platelet count 1
These scores help stratify patients for further evaluation with elastography or specialist referral. 2
Prognostic Scoring Systems
Perform Child-Pugh and MELD score calculations every 6 months for patients with established cirrhosis. 2, 1
Child-Pugh Score Components
- Serum albumin
- Bilirubin
- PT/INR
- Clinical assessment of ascites and encephalopathy 2
MELD Score Components
- Serum bilirubin
- Creatinine
- INR 2
The MELD score ranges from 6 (less ill) to 40 (gravely ill) and was originally designed to assess mortality risk; scores ≥15 warrant liver transplantation evaluation. 2, 3
Albumin-Bilirubin (ALBI) Grade
- Uses serum albumin and bilirubin levels
- Particularly helpful in predicting survival in patients with stable decompensated cirrhosis 2
Portal Hypertension Assessment
Evaluate for clinical signs of portal hypertension through laboratory surrogates. 2
- Thrombocytopenia: Platelet count <150,000 suggests clinically significant portal hypertension 2
- White blood cell count: May be decreased due to hypersplenism 2
- Splenomegaly on imaging: Correlates with portal hypertension 2
Ascites-Specific Testing
When ascites is present or develops, perform diagnostic paracentesis immediately without delay to rule out spontaneous bacterial peritonitis (SBP). 1
Mandatory Ascitic Fluid Tests
- Cell count with differential: Absolute neutrophil count ≥250 cells/mm³ indicates SBP 1
- Ascitic fluid total protein: Helps classify ascites type 1
- Serum-ascites albumin gradient (SAAG): SAAG ≥1.1 g/dL indicates portal hypertension 1
- Ascitic fluid culture: Inoculate blood culture bottles at bedside 1
Additional Tests Based on Clinical Suspicion
- Cytology (if malignancy suspected)
- Amylase (if pancreatic ascites suspected)
- BNP (if cardiac ascites suspected)
- Adenosine deaminase (if tuberculous peritonitis suspected) 1
Monitoring Schedule
For patients with established cirrhosis, perform clinical assessment with laboratory tests every 6 months. 1, 3
This includes:
- Complete hepatic function panel
- Child-Pugh score calculation
- MELD score calculation
- Albumin-bilirubin grade
- Ultrasound surveillance for hepatocellular carcinoma 1
Critical Pitfalls to Avoid
Do not use high thresholds for liver enzyme abnormalities; delayed diagnosis occurs when waiting for values >1.5-2× upper limit of normal. 1
- Use age and sex-normative values for interpretation 1
- Persistent abnormalities over 3-6 months warrant further evaluation even if mildly elevated 1
- Perform screening during clinical stability to avoid transient elevations from acute illness 1
- Normal liver blood tests do not rule out advanced fibrosis or cirrhosis—consider elastography in high-risk patients even with normal labs 2
Limitations of Standard Coagulation Tests
Traditional coagulation tests (PT, INR, aPTT) are inadequate and often misleading in cirrhosis because they only partially evaluate hemostasis and neglect counterbalanced factors. 2
- These tests systematically underestimate coagulation capacity in cirrhosis 2
- Global tests like thromboelastography (TEG) or rotational thromboelastometry (ROTEM) show that patients with cirrhosis often have normal to elevated thrombin-generating capacity 2
- Do not use PT/INR alone to assess bleeding risk before procedures 2
When to Consider Liver Biopsy
Liver biopsy is not generally recommended for all patients with suspected cirrhosis but should be considered when non-invasive test results are inconclusive or when suspicion exists for competing liver disease. 2
Approximately 20% of patients with alcohol use disorder and abnormal liver tests have a co-existing etiology of liver disease. 2 Biopsy carries approximately 2% risk of severe complications including intrahepatic bleeding and pneumothorax. 2