1. FibroTest in the diagnosis of HBV
Publications on diagnostic performance
FT in diagnostic of HBV

2. In this Presentation 1. Diagnosis and clinical options 2.
First validation of FibroTest-ActiTest in HBV 3.
FibroTest in histological changes 4.
FibroTest, combinations and comparison with other non invasive methods 5.
Meta-analysis
FT in diagnostic of HBV

3. Diagnosis and clinical options
Positive serology
FT in diagnostic of HBV
Poynard et al, Comp Hepatol 2004

4. First HBV validation
FT in diagnostic of HBV

5. Myers RP et al, J Hepatol 2003 – First Validation in HBV
Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B (n=209)
Conclusions
Sensibility analyse: markers nt affected by ethnicity, HBV DNA or HBV status
In AgHbe positive patients: FT more accurate than AST (AUROC: 0,89 vs 0,79
AST vs METAVIR Inflammation grade
ActiTest vs METAVIR Inflammation grade
FibroTest : useful for identification of HBV-related fibrosis
ActiTest: useful for excluding significant necroinflammation
AST vs METAVIR Fibrosis stage
ActiTest vs METAVIR Fibrosis stage
FT in diagnostic of HBV

6. FibroTest in Histological changes
FT in diagnostic of HBV

7. Poynard et al, Am J of hepatology 2005
Longitudinal Assessment of Histology Surrogate Markers (FibroTest–ActiTest) During Lamivudine Therapy in Patients with Chronic Hepatitis B Infection
Conclusion
In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics.
FT–AT should be useful in the noninvasive follow-up of lamivudine treatment.
AUROC of FirboTest ActiTest =: 0,74-077, similar as the one observed in patients with HCV
FT in diagnostic of HBV

8. Poynard et al Am J G 2005 0.73 0.52 Conclusion
Kinetics of fibrosis according to baseline stages in HBV patients
treated with lamivudine 2 years (n=283)
0.00
0.25
0.50
0.75
1.00
Baseline
6 mo
12 mo
24 mo
FibroTest
0.73
0.52
Conclusion
44 Cirrhosis: 42 (95%) improvement at 24 months
Significant regression (>0.30) in 14/44 (32%)
F2F3F4 P=0.01
F0F1 NS
FT in diagnostic of HBV

9. Poynard et al, AASLD 2007
Impact of adefovir dipivoxil on liver fibrosis and activity assessed with biochemical markers (FibroTest-ActiTest) in patients infected by Hepatitis B Virus
Study group
Chronic hepatitis B (HBeAg+ and HBeAg-)
Randomized in two placebo-controlled trials of ADV
Available paired liver biopsies and FibroTest-ActiTest at baseline and after 48 weeks of treatment
Liver biopsies scored for fibrosis and inflammation, utilizing Knodell, Ishak and METAVIR scoring systems, one blinded central pathologist
Methods
AUROCs for the diagnosis of advanced fibrosis, cirrhosis, and moderate-severe activity
Sensitivity analyses: ethnicity, biopsy size, HBeAg status
Impact of treatment assessed on liver injury (biopsy and FibroTest-ActiTest) according to baseline stage, and virological response
Analysis of discordance between biopsy and FibroTest
FT in diagnostic of HBV
Poynard et al, AASLD 2007

10. Poynard et al, AASLD 2007 - Results
FibroTest and Fibrosis Stages
Ishak Stages
METAVIR stage
FT in diagnostic of HBV

11. Poynard et al, AASLD 2007 - Results
ActiTest and Necro-Inflammatory Features
Peri Portal Necrosis Knodell Score
Lobular necrosis Knodell Score
Portal Inflammation Knodell Score
FT in diagnostic of HBV

12. Poynard et al, AASLD 2007 - Results
ActiTest and Necro-Inflammatory Scoring System
Ishak Activity grade
METAVIR Activity grade
FT in diagnostic of HBV

13. Poynard et al, AASLD 2007 - Results
Impact of HBV treatment on fibrosis: Biopsy versus FibroTest
48 weeks with adefovir (n=304) or placebo (n=158)
Biopsy
FibroTest
P<0.0001
P<0.0001
FT in diagnostic of HBV

14. Poynard et al, AASLD 2007 - Results
Impact of HBV treatment on fibrosis in HBV Virological Responders with advanced baseline fibrosis
97 treated with adefovir, 9 treated with placebo (spontaneous clearance)
Biopsy
FibroTest
P<0.0001
P<0.0001
P=0.02
FT in diagnostic of HBV

15. Poynard et al, AASLD 2007 - Conclusions
Discordance analysis
29% discordances estimated by the classical analysis considering biopsy as the gold standard
29 discordant cases had incoherence between virological response and histological response
Failure attributable to biopsy 66% (19/29) false positive median 11mm, false negative median 7-mm
Failure attributable to FT-AT 34% (10/29)
If these estimates are true the real rates of patients misclassified using FT-AT is 10% (34% of 29%)
Conclusions
Provides an accurate quantitative estimate of liver fibrosis and necro-inflammatory activity
Is effective and very sensitive as noninvasive marker of histological changes during treatment or followup without treatment
FT in diagnostic of HBV

16. Combination and comparison with other non invasive methods
FibroScan, APRI, Mp3
FT in diagnostic of HBV

17. Sebastiani et al, J Hepatol 2006
Diagnostic performance of non-invasive biomarkers of liver fibrosis in chronic hepatitis B (n=110)
Results
Diagnosis of F2F3F4 & F4
Se: 89,5% & 62,5%
Sp: 78,8% & 98,4%
NPV: 64,7% & 95,4%
PPV (for F4): 83%
FibroTest correctly classfied all patients
Conclusions
Fibrotest presents with the best accuracy in all the subgroups of patients with chronic liver disease
Combination of markers should reduce the need for liver biopsy
HEPATITIS B (AUC)
APRI
FIBROTEST
0.72
0.85
0.64
0.76
>F2 F4
FT in diagnostic of HBV

18. Sebastiani et al, J Hepatol 2006 – Safe Biopsy
Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY) Stepwise modelling aimed to achive accuracy> 95%
For significant fibrosis
For cirrhosis
FT in diagnostic of HBV

19. Sebastiani et al, J Hepatol 2006 – Safe Biopsy
Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY) INTERIM ANALYSIS ON 210 HBV CASES
SAFE BIOPSY for
SIGNIFICANT FIBROSIS
SAFE BIOPSY for CIRRHOSIS
Accuracy (%) 96 90
Saved biopsies (%) 45 77
Saved cost (%) 44 75
FT in diagnostic of HBV

20. Castera L. et al, J Hepatol 2006
Prospective comparison in FibroScan (FS) and FibroTest (FT) in inactive hepatitis B carriers
Study Group
Cohort of 154 HBV patients, among these 40 inactive carriers
Method
FibroTest and FibroScan given the same day
Results
Fibroscan Failure: 6
Median value (FS and FT) significantly lower in inactive carriers than in other patients
Agreement of FS and FT for the absence of significant fibrosis in 83% of the patients
Conclusion
Non invasive assessment of fibrosis in HBV inactive carriers per FT and FS could be useful
FT in diagnostic of HBV

21. Hilleret et al, J Hepatol 2006
Diagnostic accuracy of mp3 score compared to hyaluronate and FibroTest for evaluating liver fibrosis in chronic hepatitis B
Diagnostic accuracy evaluated by AUROC for discriminating F0F1F2 vs F3F4 HA
MP3 FT
Comments
MP3 score greater than 0.50 had a PPV for extensive fibrosis of 82%, while score lower than 0.30 had a NPV of 88%.
When combining MP3 (0.40) and HA (80), the PPV increased to 92% for F3F4
0.82
0.81
Conclusions
MP3, HA and FT have a good accuracy in HBV infection in predicting extensive fibrosis, especially when used in combination.
Especially useful for of inactive carriers who might have cirrhosis.
FT in diagnostic of HBV

22. Meta analysis
FT in diagnostic of HBV

23. FibroTest Meta-Analysis
Poynard et al, clin chem 2007
FibroTest Meta-Analysis
30 Published Studies
6.378 Patients
AUROC=0.84 ( )
for F2F3F4
The best you can obtain with 20mm biopsy is Bedossa 2003
FT in diagnostic of HBV