FT in diagnostic of HBV1 FibroTest in the diagnosis of HBV Publications on diagnostic performance.
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Transcript of FT in diagnostic of HBV1 FibroTest in the diagnosis of HBV Publications on diagnostic performance.
FT in diagnostic of HBV 1
FibroTest in the FibroTest in the diagnosisdiagnosis of of HBVHBV
Publications on diagnostic performance
FT in diagnostic of HBV 2
1.1. Diagnosis and clinical optionsDiagnosis and clinical options
2.2. First validation of FibroTest-ActiTest in HBVFirst validation of FibroTest-ActiTest in HBV
3.3. FibroTest in histological changesFibroTest in histological changes
4.4. FibroTest, combinations and comparisonFibroTest, combinations and comparison with other non invasive methods with other non invasive methods
5.5. Meta-analysisMeta-analysis
In this PresentationIn this Presentation
FT in diagnostic of HBV 3
Results interpretable no risk of false positive/negative
Not interpretable Risk of false
positive/negative*
Repeat Test or perform
elastography/ biopsyNo biopsy mandatory
Treatment TreatmentOr follow-up**
Follow-up** with FibroTest
Treatment Or follow-up
95% 5%
(For liver injuries Assessment)
Diagnosis and clinical optionsDiagnosis and clinical options
Positive serologyPositive serology
Poynard et al, Comp Hepatol 2004
FT in diagnostic of HBV 4
First HBV validationFirst HBV validation
FT in diagnostic of HBV 5
Myers RP et al, J Hepatol 2003 Myers RP et al, J Hepatol 2003 – First Validation in HBV– 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 0,79AST 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 changesFibroTest in Histological changes
FT in diagnostic of HBV 7
Poynard et al, Am J of hepatology 2005Poynard et al, Am J of hepatology 2005
Longitudinal Assessment of Histology Surrogate Markers (FibroTest–Longitudinal Assessment of Histology Surrogate Markers (FibroTest–ActiTest) During Lamivudine Therapy in Patients with Chronic Hepatitis B ActiTest) During Lamivudine Therapy in Patients with Chronic Hepatitis B
InfectionInfection
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
F0F1 NS
0.00
0.25
0.50
0.75
1.00
Baseline 6 mo 12 mo 24 mo
FibroTest
0.73
0.52
Poynard et al Am J G 2005Poynard et al Am J G 2005
Kinetics of fibrosis according to baseline stages in HBV patients Kinetics of fibrosis according to baseline stages in HBV patients treated with lamivudine 2 years (n=283)treated with lamivudine 2 years (n=283)
Conclusion
- 44 Cirrhosis: 42 (95%) improvement at 24 months
- Significant regression (>0.30) in 14/44 (32%)
F2F3F4 P=0.01
FT in diagnostic of HBV 9
Poynard et al, AASLD 2007Poynard et al, AASLD 2007
Impact of adefovir dipivoxil on liver fibrosis and activity assessed with Impact of adefovir dipivoxil on liver fibrosis and activity assessed with biochemical markers (FibroTest-ActiTest) in patients infected by biochemical markers (FibroTest-ActiTest) in patients infected by
Hepatitis B VirusHepatitis B Virus
Poynard et al, AASLD 2007
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 10
Poynard et al, AASLD 2007 - ResultsPoynard et al, AASLD 2007 - Results
• FibroTest and Fibrosis StagesFibroTest and Fibrosis Stages
Ishak Stages METAVIR stage
FT in diagnostic of HBV 11
Poynard et al, AASLD 2007 - ResultsPoynard et al, AASLD 2007 - Results
• ActiTest and Necro-Inflammatory FeaturesActiTest and Necro-Inflammatory Features
Peri Portal NecrosisKnodell Score
Lobular necrosis Knodell Score
Portal InflammationKnodell Score
FT in diagnostic of HBV 12
Poynard et al, AASLD 2007 - ResultsPoynard et al, AASLD 2007 - Results
• ActiTest and Necro-Inflammatory Scoring SystemActiTest and Necro-Inflammatory Scoring System
Ishak Activity grade METAVIR Activity grade
FT in diagnostic of HBV 13
,4400 ,4500
,4000,4200
Adefovir PlaceboBaseline 48 weeks
P<0.00011,5800
1,7800
1,4100
1,8000
Adefovir Placebo
Baseline
48 weeks
P<0.0001
Biopsy FibroTest
• Impact of HBV treatment on fibrosis: Biopsy versus FibroTest48 weeks with adefovir (n=304) or placebo (n=158)
Poynard et al, AASLD 2007 - ResultsPoynard et al, AASLD 2007 - Results
FT in diagnostic of HBV 14
Biopsy FibroTest
• Impact of HBV treatment on fibrosis in HBV Virological Responders with advanced baseline fibrosis97 treated with adefovir, 9 treated with placebo (spontaneous clearance)
Poynard et al, AASLD 2007 - ResultsPoynard et al, AASLD 2007 - Results
1,9300
2,4400
1,6300
2,4400
Adefovir Biopsy Placebo Biopsy
Baseline
48 weeks
P<0.0001,7000 ,6500
,5800
,4500
Adefovir FibroTest Placebo FibroTest
Baseline
48 weeks
P<0.0001 P=0.02
FT in diagnostic of HBV 15
Poynard et al, AASLD 2007 - ConclusionsPoynard 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 Combination and comparison with other non invasive methodswith other non invasive methods
FibroScan, APRI, Mp3
FT in diagnostic of HBV 17
Sebastiani et al, J Hepatol 2006Sebastiani et al, J Hepatol 2006
HEPATITIS B (AUC)
APRI FIBROTEST
0.72 0.85
0.64 0.76
• Diagnostic performance of non-invasive biomarkers of liver fibrosis in chronic hepatitis B (n=110)
>F2
F4
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
FT in diagnostic of HBV 18
Sebastiani et al, J Hepatol 2006 Sebastiani et al, J Hepatol 2006 – Safe Biopsy– Safe Biopsy
• Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY) Stepwise modelling aimed to achive accuracy> 95%
For significant fibrosis For cirrhosis
APRI
No Fibrosis(low accuracy)
Significant fibrosis(high accuracy)
Unclassified
FIBROTEST
F2-F3-F4(high accuracy)F0-F1
(low accuracy)
>94% accuracy Liver biopsy not needed
Liver biopsy needed
APRI
Cirrhosis(low accuracy)Unclassified
FIBROTEST
F4(high accuracy)
F0-F1(high accuracy)
>95% accuracy Liver biopsy not needed
LiverLiver biopsybiopsy neededneeded
F2-F3 (low accuracy)
No cirrhosis(high accuracy)
FT in diagnostic of HBV 19
Sebastiani et al, J Hepatol 2006 Sebastiani et al, J Hepatol 2006 – Safe Biopsy– 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 90Saved biopsies (%)
45 77
Saved cost (%) 44 75
FT in diagnostic of HBV 20
Castera L. et al, J Hepatol 2006Castera 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 2006Hilleret 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 F3F4HA 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 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 analysisMeta analysis
FT in diagnostic of HBV 23
Poynard et al, clin chem 2007Poynard et al, clin chem 2007
FibroTest Meta-Analysis
30 Published Studies
6.378 Patients
2001-2006
AUROC=0.84 (0.83-0.86)
for F2F3F4
The best you can obtain with 20mm biopsy is 0.90 Bedossa 2003