What is the diagnostic workup for a patient with suspected cirrhosis (scarring of the liver)?

Diagnostic Workup for Cirrhosis

Begin with a comprehensive hepatic function panel including bilirubin, AST, ALT, alkaline phosphatase, albumin, PT/INR, platelet count, complete blood count, and renal function tests, followed by abdominal ultrasound and etiologic workup to identify the underlying cause. 1

Initial Laboratory Assessment

The diagnostic workup requires a systematic approach starting with laboratory evaluation:

Core Hepatic Function Panel

• AST and ALT are typically elevated in active liver injury, with AST/ALT ratio often >1 in cirrhosis 1
• Alkaline phosphatase may be elevated, particularly in cholestatic liver disease 1
• GGT is useful for detecting hepatobiliary involvement and calculating fibrosis indices 1
• Bilirubin (total and direct): elevated conjugated bilirubin indicates advanced disease or biliary obstruction 1
• Albumin levels are decreased in impaired synthetic function and are part of prognostic scoring 1
• PT/INR values are prolonged in impaired hepatic synthetic function and are critical for Child-Pugh and MELD scoring 1
• Platelet count is specifically important as thrombocytopenia suggests portal hypertension and is a surrogate marker for advanced disease 1
• Creatinine and BUN are essential for MELD score calculation and detecting hepatorenal syndrome 1

Etiologic Workup

Once cirrhosis is suspected, determine the underlying cause:

• Hepatitis B panel (HBsAg, anti-HBc) and hepatitis C antibody with viral load confirmation in all positive cases 1, 2
• Ferritin and transferrin saturation to screen for hemochromatosis 1
• Autoimmune markers (ANA, ASMA, anti-LKM) if etiology is unclear 1, 2
• Alpha-1 antitrypsin level to screen for alpha-1 antitrypsin deficiency 1
• Ceruloplasmin for Wilson disease, particularly in younger patients 1
• Assess alcohol intake history and metabolic syndrome components (obesity, diabetes) 2, 3

Initial Imaging Studies

Abdominal Ultrasound (First-Line)

Abdominal ultrasound is the initial imaging modality with 65% to 95% sensitivity and 98% positive predictive value for detecting cirrhosis. 1

Look for specific morphological features:

• Nodular liver surface (most accurate finding: 86% sensitivity on undersurface vs 53% on superior surface) 1
• Right lobe atrophy with caudate lobe and lateral segment hypertrophy 2, 4
• Increased caudate-to-right lobe ratio (modified ratio >0.90) 4
• Ascites (can detect as little as 100 mL) 4
• Splenomegaly and other signs of portal hypertension 2

Important caveat: Morphological changes may not be apparent until very advanced stages, and ultrasound evaluation is operator-dependent with significant overlap between steatosis and cirrhosis appearance. 4

Non-Invasive Fibrosis Assessment

Transient Elastography (FibroScan)

• Values >15 kPa strongly suggest compensated advanced chronic liver disease 2, 4
• For hepatitis C specifically, a cutoff of 12.5 kPa has 86% sensitivity and 91% specificity for cirrhosis diagnosis 2, 4
• For alcoholic liver disease, use 12.5 kPa cutoff prioritizing sensitivity to avoid missing cases 1

Critical pitfalls: Results can be affected by recent meals, inflammation, hepatic congestion, and reduced accuracy with hepatic iron deposition. 4

Serum Fibrosis Indices

Calculate non-invasive markers using laboratory values:

• APRI (AST-to-platelet ratio index) 1, 3
• FIB-4 score 1, 3
• GPR (GGT-to-platelet ratio) 1

These are most useful for identifying patients with no to minimal fibrosis or advanced fibrosis. 3

Advanced Imaging When Indicated

MR Elastography

MR elastography is currently the most accurate imaging modality for diagnosis and staging of hepatic fibrosis and should be performed when available, particularly in obese patients where ultrasound has limited penetration. 2, 4

Multiphasic CT or MRI

Perform when:

• Hepatocellular carcinoma is suspected (both have similar diagnostic performance) 1
• Better characterization of liver morphology is needed 2
• Evaluating vascular anatomy and extent of disease 2

MRI is superior to CT for visualizing bands of fibrosis on both noncontrast and contrast-enhanced sequences. 2, 4

Clinical Assessment

Identify specific signs of cirrhosis and portal hypertension:

• Jaundice, ascites, hepatic encephalopathy 2
• Spider angiomas, palmar erythema 2, 4
• Splenomegaly 2, 4
• Variceal bleeding history 2
• Performance status and nutritional state 5

Assessment for Portal Hypertension

• Upper endoscopy should be performed to evaluate for esophageal varices and hypertensive gastropathy in all patients with newly diagnosed cirrhosis unless low-risk criteria are met (platelets >150,000 and liver stiffness <20 kPa) 1, 2
• Transjugular measurement of hepatic-venous pressure gradient may be considered in select cases 2

Hepatocellular Carcinoma Surveillance

All patients with confirmed cirrhosis should undergo HCC surveillance with ultrasound every 6 months, combined with serum AFP estimation. 2

High-risk populations requiring surveillance include:

• Males and females with HBV or HCV cirrhosis 2
• Genetic hemochromatosis cirrhosis 2
• Males with alcohol-related cirrhosis who are abstinent or likely to comply with treatment 2
• Males with primary biliary cirrhosis 2

Liver Biopsy Considerations

Avoid liver biopsy when unnecessary due to its invasive nature, risk of complications, sampling errors, and limited acceptance for longitudinal monitoring. 2, 4

Reserve biopsy for:

• Non-invasive evaluation results are indeterminate 2, 4, 6
• Etiology of liver disease remains unknown 6, 7
• Results may alter management 2, 4, 6
• Never biopsy potentially operable lesions due to risk of tumor seeding 2

Prognostic Scoring

Calculate at initial diagnosis:

• Child-Pugh score (using bilirubin, albumin, PT/INR, ascites, encephalopathy) 1
• MELD-Na score (incorporates bilirubin, INR, creatinine, and sodium for improved prognostic accuracy) 1

Ascites-Specific Testing (If Present)

Perform diagnostic paracentesis immediately in all patients with new-onset grade 2 or 3 ascites or any hospitalized patient with cirrhosis: 1, 2

• Ascitic fluid cell count with differential 1
• Ascitic fluid total protein 1
• Serum-ascites albumin gradient (SAAG) to confirm portal hypertension (≥1.1 g/dL indicates portal hypertension) 1, 2
• Ascitic fluid culture (bedside inoculation of 10 mL into blood culture bottles) 2

Common Diagnostic Pitfalls

• Do not wait for liver enzymes to reach >1.5-2× upper limit of normal before pursuing workup; use age and sex-normative values as persistent abnormalities over 3-6 months warrant evaluation even if mildly elevated 1
• Perform screening during clinical stability to avoid transient elevations from acute illness 1
• Do not delay diagnostic paracentesis to rule out spontaneous bacterial peritonitis in hospitalized patients with ascites 1
• Recognize that cirrhosis can be clinically silent until decompensation occurs, making proactive screening essential in at-risk populations 4, 7, 8