Non-Invasive Testing for Liver Fibrosis and Cirrhosis
Transient elastography (FibroScan) is the most accurate non-invasive method for detecting cirrhosis and should be the primary choice when available, while serum biomarkers (APRI, FIB-4) serve as acceptable alternatives in resource-limited settings or when elastography is unavailable. 1
Primary Recommendation: Transient Elastography (FibroScan)
FibroScan outperforms all serum biomarkers for detecting both significant fibrosis and cirrhosis and should be prioritized as first-line testing. 1
Diagnostic Thresholds for FibroScan
- For significant fibrosis (≥F2): Use >7.0 kPa cutoff (sensitivity 75.1%, specificity 79.3%) 1, 2
- For advanced fibrosis (≥F3): Use >9.5 kPa cutoff (sensitivity 80.4%, specificity 85.2%) 1
- For cirrhosis (F4): Use >12.5 kPa cutoff (sensitivity 82.6%, specificity 89.0%) 1, 2
Clinical Interpretation Algorithm
- <7.0 kPa: Low probability of significant fibrosis; discharge to primary care with lifestyle counseling and repeat testing every 1-3 years in at-risk populations 1, 2
- 7.0-12.5 kPa: Significant fibrosis present; prioritize for antiviral treatment to prevent progression 2
- >12.5 kPa: Cirrhosis likely; immediate antiviral treatment plus screening for varices and hepatocellular carcinoma 2
Technical Considerations
- FibroScan fails in approximately 5% of cases, predominantly in obese patients (BMI >25 kg/m²) 3
- Success rate <60% occurs in 16% of cases, again primarily related to obesity 3
- The technique is rapid, reproducible (ICC 0.982), and provides immediate results 3, 4
Alternative Serum Biomarkers
When to Use Serum Markers
Use serum biomarkers when FibroScan is unavailable, fails due to obesity, or in resource-limited settings where elastography is not accessible. 1
APRI (Aspartate Aminotransferase-to-Platelet Ratio Index)
For chronic hepatitis B:
- Significant fibrosis (≥F2): Use >0.5 cutoff (sensitivity 72.9%, specificity 64.7%) 1
- Cirrhosis (F4): Use >1.0 cutoff (sensitivity 59.4%, specificity 73.9%) 1
The WHO 2024 guidelines specifically lowered the APRI threshold from >2.0 to >0.5 for significant fibrosis to minimize false negatives, accepting that 26.2% of treated patients may not have significant fibrosis but ensuring only 6.8% with disease are missed. 1
FIB-4 Index
For NAFLD and general chronic liver disease:
- Low risk: <1.3 (or <2.0 if age >65 years) rules out advanced fibrosis 1
- High risk: >2.67 (or >3.25 if age >65 years) indicates likely advanced fibrosis 1
- Indeterminate: 1.3-2.67 requires second-tier testing 1
Important caveat: FIB-4 and NFS are not validated in patients under 35 years of age and should be interpreted with extreme caution in this population. 1
FibroTest
FibroTest demonstrates superior performance to APRI and FIB-4 but requires multiple specialized laboratory tests:
- Chronic hepatitis B: AUROC 0.90 for significant fibrosis (sensitivity 79%, specificity 93%) and AUROC 0.87 for cirrhosis (sensitivity 80%, specificity 84%) 1, 5
- Chronic hepatitis C: AUROC 0.87 for significant fibrosis with cutoff 0.48 (sensitivity 75%, specificity 85%) 5
FibroTest is more expensive and time-consuming than simple serum markers but provides better diagnostic accuracy by incorporating direct markers of extracellular matrix turnover. 1, 5
Dual Testing Strategy for Maximum Accuracy
Combining two non-invasive tests significantly improves diagnostic accuracy and should be implemented when feasible. 1
Recommended Algorithm for Indeterminate Results
- Initial screening: Use FIB-4 or APRI in all patients 1
- Low-risk results: Discharge to primary care with lifestyle modification 1
- Indeterminate results: Perform second-tier testing with either:
- High-risk results: Refer to hepatology regardless of second test 1
Managing Discordant Results
When two non-invasive tests disagree:
- Perform abdominal ultrasound to identify cirrhosis signs (nodular surface, splenomegaly, portosystemic collaterals) 1
- Consider upper endoscopy to assess for varices 1
- Liver biopsy may be necessary in select cases with persistent discordance 1
Alternative Elastography Techniques
Point Shear Wave Elastography (pSWE/ARFI)
- Performance equivalent to FibroScan for detecting significant fibrosis and cirrhosis (AUROC 0.87 for both significant fibrosis and cirrhosis) 1
- Better validated in chronic hepatitis C than hepatitis B, HIV-HCV coinfection, or NAFLD 1
- Performs better for cirrhosis detection than significant fibrosis 1
2D Shear Wave Elastography (2D-SWE)
- May outperform FibroScan in some studies, particularly for significant fibrosis in chronic hepatitis B (AUROC 0.88-0.97 vs. 0.78-0.84) 1
- Cutoff values: 7.1-8.2 kPa for significant fibrosis, 8.0-21.4 kPa for cirrhosis 1
- Currently under investigation but appears at least equivalent to FibroScan and pSWE/ARFI 1
MR Elastography
- Conflicting data on superiority over FibroScan; further validation needed 1
- Not recommended as first-line due to cost, availability, and lack of clear superiority 1
Disease-Specific Considerations
Chronic Hepatitis C
- FibroScan and serum biomarkers have equivalent performance for detecting significant fibrosis 1
- FibroScan is superior for detecting cirrhosis 1
- Post-SVR caveat: Pre-treatment cutoffs cannot be used after achieving sustained virologic response; NITs decline due to reduced inflammation, not necessarily fibrosis regression 1
Chronic Hepatitis B
- FibroScan cutoffs: >7.0 kPa (≥F2), >9.5 kPa (≥F3), >12.5 kPa (F4) 1, 2
- Both pSWE and FibroScan are influenced by ALT levels; higher cutoffs needed when ALT is elevated 1
NAFLD
- Use FIB-4 as initial screening tool 1
- FibroScan LSM <8 kPa allows discharge to primary care 1
- Patients with FIB-4 1.3-2.67 or LSM 8-10 kPa require specialized follow-up if MASLD or harmful alcohol intake present 1
Common Pitfalls to Avoid
- Do not use pre-treatment cutoffs post-SVR in hepatitis C patients; serum markers decline with reduced inflammation independent of fibrosis changes 1
- Do not rely on FIB-4 or NFS in patients <35 years; these scores are not validated in younger populations 1
- Do not ignore obesity as a cause of FibroScan failure; consider serum markers as primary testing in BMI >30 kg/m² 3
- Do not use single high APRI cutoffs alone (>1.5-2.0); this misses >50% of cirrhosis cases 1
- Do not discharge patients with indeterminate results without second-tier testing or specialist evaluation 1