What is the diagnostic workup for liver cirrhosis?

Workup for Liver Cirrhosis

The diagnostic workup for liver cirrhosis should begin with clinical examination for specific signs (ascites, spider angiomas, palmar erythema, splenomegaly), followed by comprehensive laboratory testing, abdominal ultrasound, and transient elastography (FibroScan), reserving liver biopsy only for indeterminate cases or when results would alter management. 1, 2, 3

Initial Clinical and Laboratory Assessment

Clinical examination should specifically assess for:

• Ascites (perform percussion of flanks and test for shifting dullness) 1
• Spider angiomas, palmar erythema, and splenomegaly as signs of portal hypertension 2
• Physical stigmata of chronic liver disease 4

Essential laboratory tests include:

• Complete blood count (CBC) with platelet count 4, 5
• Comprehensive metabolic panel: AST, ALT, GGT, alkaline phosphatase, bilirubin 4
• Hepatic synthetic function: serum albumin, gamma globulins, prothrombin time/INR 4, 5
• Viral hepatitis serologies (HBsAg, anti-HBs, anti-HBc, HCV antibody) 4, 5
• Ferritin and transferrin saturation (to exclude hemochromatosis) 5

Imaging Studies

Abdominal ultrasound is the recommended initial imaging modality and should evaluate: 4, 1, 2

• Liver surface nodularity (most accurate sonographic finding for cirrhosis, with 86% sensitivity on undersurface vs 53% on superior surface) 4
• Right lobe atrophy, caudate lobe hypertrophy, and lateral segment hypertrophy of left lobe 2
• Ascites (detectable from 100 ml) 1, 2
• Portal vein patency and direction of flow 2

Ultrasound has 65-95% sensitivity and 98% positive predictive value for detecting cirrhosis. 4

Non-Invasive Fibrosis Assessment

Transient elastography (FibroScan) is the recommended non-invasive method for assessing liver stiffness: 4, 1, 2

• Values >15 kPa strongly suggest compensated advanced chronic liver disease (cACLD) and cirrhosis 1, 2
• Offers higher diagnostic accuracy than serum biomarkers for detecting cirrhosis 4
• Better at excluding than confirming advanced fibrosis 4

Important caveats for elastography:

• Results may be confounded by severe inflammation with high ALT levels 4
• Reduced accuracy in patients with hepatic iron deposition 2
• Can be affected by recent meals, parenchymal edema, cholestasis, and cardiogenic hepatic congestion 2

Alternative scoring systems for fibrosis assessment include: 5

• AST to platelet ratio index (APRI)
• Fibrosis-4 (FIB-4) score
• These are most useful for identifying patients with no fibrosis or advanced fibrosis 5

Advanced Imaging (When Indicated)

MRI with MRCP should be considered when: 4

• Ultrasound and clinical workup are inconclusive for etiology 4
• Concern exists for primary sclerosing cholangitis or primary biliary cirrhosis 4
• Better visualization of fibrosis bands is needed (superior to CT) 2

MR elastography is currently the most accurate imaging modality for diagnosis and staging of hepatic fibrosis and compares favorably with ultrasound shear wave elastography, particularly in patients with obesity. 2

Contrast-enhanced CT can demonstrate:

• Parenchymal heterogeneity 2
• Enhancement of lattice-like macroscopic bands of fibrosis 2

Etiologic Workup

Systematically exclude co-morbidities and alternative causes: 4

• Alcoholic liver disease (complete history of alcohol consumption) 4
• Autoimmune hepatitis (autoantibodies) 4
• Metabolic liver disease with steatosis/steatohepatitis 4
• Co-infections: HDV, HCV, HIV 4

For hepatitis B patients specifically:

• HBeAg and anti-HBe detection (essential for determining infection phase) 4
• HBV DNA serum level (essential for diagnosis and treatment decisions) 4
• Serum HBsAg quantification (useful in HBeAg-negative infection) 4
• HBV genotype (may be useful for interferon therapy selection) 4

Test for anti-HAV antibodies and vaccinate if negative. 4

When to Perform Liver Biopsy

Liver biopsy remains the reference standard but should be reserved for: 3, 5

• Indeterminate results from non-invasive evaluation 3
• Unknown etiology of liver disease 3
• When results may alter management 3

Avoid biopsy when unnecessary due to:

• Invasive nature and risk of complications 2
• Sampling errors 2
• Limited acceptance for longitudinal monitoring 2

Diagnostic Algorithm Summary

1. Perform clinical examination focusing on signs of cirrhosis and portal hypertension 1, 2
2. Order comprehensive laboratory panel including CBC, liver function tests, viral serologies, ferritin/transferrin saturation 4, 5
3. Obtain abdominal ultrasound to assess liver morphology and detect ascites 1, 2
4. Perform transient elastography (values >15 kPa suggest cirrhosis) 1, 2
5. Consider contrast-enhanced CT or MRI if ultrasound/elastography inconclusive or to better characterize morphology 2
6. Reserve liver biopsy for indeterminate cases or when etiology remains unclear 3, 5

Common Pitfalls

• Morphological changes on conventional imaging may not be apparent until very advanced stages, limiting utility for early detection 2
• Elastography can give false readings if performed after recent meals, during active inflammation, or in hepatic congestion 2
• Progression from fibrosis to compensated to decompensated cirrhosis can be clinically silent, making early diagnosis challenging 2
• Up to 40% of cirrhosis patients are diagnosed only when presenting with complications such as hepatic encephalopathy or ascites, when median survival is already reduced to approximately 1 year 6