Is Prothrombin Time/International Normalized Ratio (PT/INR) still needed or useful in patients undergoing Hepatitis C Virus (HCV) treatment if Fibrosure and Fib-4 have been calculated to assess liver fibrosis?

PT/INR is Not Needed for Routine Fibrosis Assessment When FibroSure and FIB-4 Are Calculated Prior to HCV Treatment

PT/INR is not routinely necessary or useful for fibrosis staging when FibroSure and FIB-4 have already been calculated prior to HCV treatment, as these non-invasive tests are sufficient to rule out advanced fibrosis and guide clinical management without requiring coagulation parameters. 1

Rationale for Non-Invasive Testing Sufficiency

The 2024 EASL position paper explicitly states that blood-based scores like FIB-4 and proprietary tests (such as FibroSure) are sufficient to rule out compensated advanced chronic liver disease (cACLD) in patients with HCV prior to treatment. 1 These non-invasive tests perform well in identifying patients without advanced fibrosis, allowing most patients to be correctly classified without additional testing. 1

FIB-4 Performance Characteristics

• FIB-4 demonstrates excellent diagnostic accuracy for HCV fibrosis staging, with an FIB-4 <1.45 having a negative predictive value of 94.7% to exclude severe fibrosis with 74.3% sensitivity. 2
• For advanced fibrosis (F3-F4) in HCV, FIB-4 thresholds of 1.45 (lower) and 3.25 (upper) show high sensitivities of 82-86% and specificities of 85-90%, respectively. 1
• The 2020 EASL HCV treatment guidelines recommend FIB-4 as an inexpensive and reliable biomarker panel for initial fibrosis assessment. 1

When PT/INR Actually Matters

PT/INR becomes clinically relevant in specific contexts unrelated to initial fibrosis staging:

• Synthetic liver function assessment: PT/INR is a component of the MELD score and Child-Pugh classification, which assess hepatic synthetic function rather than fibrosis stage. 1
• Suspected decompensated cirrhosis: When clinical signs suggest hepatic decompensation (ascites, variceal bleeding, hepatic encephalopathy), PT/INR helps assess coagulopathy severity. 1
• Pre-procedural evaluation: PT/INR is needed before liver biopsy or other invasive procedures to assess bleeding risk, but this is separate from fibrosis staging itself. 1

Algorithmic Approach to Fibrosis Assessment

Step 1: Calculate FIB-4 and obtain FibroSure results 1, 3

Step 2: Interpret based on disease-specific cutoffs:

• FIB-4 <1.45: Advanced fibrosis excluded, no additional testing needed 1, 3
• FIB-4 1.45-3.25: Indeterminate zone, use FibroSure or add imaging (transient elastography) 1
• FIB-4 >3.25: Advanced fibrosis likely present 1, 2

Step 3: If discordant results between FIB-4 and FibroSure:

• Add a third non-invasive method (preferably transient elastography/FibroScan) 1
• Consider abdominal ultrasound to identify signs of cirrhosis (nodular surface, splenomegaly) 1

Step 4: Reserve PT/INR for:

• Calculating MELD score if cirrhosis is confirmed and transplant evaluation is considered 1
• Assessing synthetic function if clinical decompensation is suspected 1
• Pre-procedural assessment if liver biopsy is ultimately needed 1

Important Caveats

Combination Testing Improves Accuracy

The 2024 EASL guidelines emphasize that combining two non-invasive tests improves accuracy for identifying advanced fibrosis and cirrhosis. 1 When FibroSure and FIB-4 are both available, they provide complementary information without requiring PT/INR. 1

PT/INR is Not a Fibrosis Marker

A critical distinction: PT/INR reflects hepatic synthetic function, not fibrosis stage. 1 While PT/INR may be abnormal in advanced cirrhosis, it can be normal in significant fibrosis (F2-F3) and is not designed to stage fibrosis. 1 The GUCI score (which incorporates PT/INR) has been studied but is not widely validated or recommended in current guidelines. 4

Post-Treatment Considerations

Non-invasive test cutoffs used before HCV therapy should not be used after achieving sustained virological response (SVR). 1 Early post-SVR decreases in FIB-4 and other markers reflect decreased inflammation rather than true fibrosis regression. 1 This further supports that PT/INR adds no value to pre-treatment fibrosis assessment, as the goal is staging for treatment prioritization and post-treatment surveillance planning. 1

Age Adjustments for FIB-4

For patients ≥65 years, consider using a higher lower cutoff (2.0 instead of 1.3) to avoid false positives, as FIB-4 is affected by age. 3 This age-related limitation applies regardless of whether PT/INR is measured. 3

Clinical Bottom Line

PT/INR measurement is redundant when FibroSure and FIB-4 are already calculated for pre-treatment fibrosis assessment in HCV patients. 1 These non-invasive tests provide sufficient information to stratify patients, determine treatment urgency, and plan post-treatment surveillance without requiring coagulation studies. 1 Reserve PT/INR for situations where hepatic synthetic function assessment or procedural bleeding risk evaluation is specifically indicated. 1