Laboratory Workup for New Diagnosis of Cirrhosis
A comprehensive laboratory workup for newly diagnosed cirrhosis should include diagnostic paracentesis for ascites, liver function tests, complete blood count, coagulation studies, and non-invasive fibrosis assessment. 1, 2
Initial Laboratory Assessment
Essential Blood Tests
- Complete blood count (CBC) with platelet count
- Comprehensive metabolic panel including:
- Liver function tests (ALT, AST, alkaline phosphatase, GGT)
- Total and direct bilirubin
- Albumin
- Total protein
- Electrolytes
- Renal function (BUN, creatinine)
- Coagulation studies (PT/INR, PTT)
- Viral hepatitis serologies (HBV, HCV)
- Ferritin and transferrin saturation (to assess for hemochromatosis)
- Alpha-fetoprotein (AFP) for hepatocellular carcinoma screening
Non-invasive Fibrosis Assessment
- APRI score (AST to Platelet Ratio Index)
- APRI > 0.5 suggests significant fibrosis (≥F2)
- APRI > 1.0 suggests cirrhosis (F4) 1
- FIB-4 score
- Transient elastography (FibroScan)
- Values > 7.0 kPa suggest significant fibrosis
- Values > 12.5 kPa suggest cirrhosis 1
Diagnostic Paracentesis for Ascites
A diagnostic paracentesis is strongly recommended for all patients with new-onset ascites due to cirrhosis 1. The ascitic fluid analysis should include:
- Total protein concentration
- Serum ascites albumin gradient (SAAG)
- Cell count with differential (neutrophil count)
- Ascitic fluid culture (bedside inoculation of blood culture bottles)
- Additional tests based on clinical suspicion:
- Cytology
- Amylase
- Brain natriuretic peptide (BNP)
- Adenosine deaminase 1
An ascitic neutrophil count >250/mm³ is diagnostic of spontaneous bacterial peritonitis (SBP) and requires immediate antibiotic therapy 1.
Etiology-Specific Testing
Based on risk factors and initial findings, consider:
Alcohol-related liver disease:
- Gamma-glutamyl transferase (GGT)
- AST/ALT ratio (typically >2 in alcoholic liver disease)
Non-alcoholic fatty liver disease:
- Lipid profile
- Fasting glucose/HbA1c
- NAFLD fibrosis score
Autoimmune hepatitis:
- Antinuclear antibody (ANA)
- Anti-smooth muscle antibody (ASMA)
- Immunoglobulin levels (IgG, IgM, IgA)
Primary biliary cholangitis:
- Anti-mitochondrial antibody (AMA)
Primary sclerosing cholangitis:
- Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)
Wilson's disease:
- Ceruloplasmin
- 24-hour urinary copper
Alpha-1 antitrypsin deficiency:
- Alpha-1 antitrypsin level
Prognostic Scoring and Monitoring
- Calculate Child-Turcotte-Pugh (CTP) score
- Calculate Model for End-Stage Liver Disease (MELD) score
- These scores should be recalculated every 6 months for monitoring 2
Screening for Complications
Hepatocellular carcinoma (HCC):
- Ultrasound every 6 months
- Consider alpha-fetoprotein in combination with ultrasound 2
Esophageal varices:
- Upper endoscopy for screening
Hepatic encephalopathy:
- Ammonia level (though clinical assessment is more important)
- Number connection test or other cognitive assessments
Important Considerations
- Routine measurement of prothrombin time and platelet count before diagnostic paracentesis is not recommended 1
- Liver biopsy is generally not required for diagnosis when clinical, laboratory, and imaging findings are consistent with cirrhosis 1, 3
- Non-invasive tests are most useful in identifying patients with no/minimal fibrosis or advanced fibrosis 3
- Laboratory tests should be repeated every 3-6 months for ongoing monitoring 2
Pitfalls to Avoid
- Do not delay diagnostic paracentesis in patients with new-onset ascites
- Do not withhold paracentesis due to concerns about coagulopathy, as routine correction of INR is not recommended 1
- Avoid relying solely on a single non-invasive test; combining different modalities improves diagnostic accuracy
- Remember that APRI and FIB-4 scores may be less accurate in certain conditions (e.g., acute hepatitis with high transaminases)
- Do not forget to screen for hepatocellular carcinoma at diagnosis and then every 6 months thereafter
Following this comprehensive laboratory workup will help establish the diagnosis, determine the etiology, assess the severity, and guide appropriate management of patients with newly diagnosed cirrhosis.