Transcript Diapositive 1

FibroTest in the diagnosis of HBV
Publications on diagnostic performance
FT in diagnostic of HBV
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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
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Diagnosis and clinical options
Positive serology
(For liver injuries
Assessment)
95%
Results interpretable
 no risk of false
positive/negative
5%
Repeat Test or
perform
elastography/ biopsy
No biopsy mandatory
Treatment
Poynard et al, Comp Hepatol 2004
Treatment
Or follow-up**
Not interpretable
Risk of false
positive/negative*
Follow-up** with
FibroTest
FT in diagnostic of HBV
Treatment
Or follow-up
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First HBV validation
FT in diagnostic of HBV
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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
AST vs METAVIR Inflammation grade
ActiTest vs METAVIR Inflammation grade
 In AgHbe positive patients: FT
more accurate than AST
(AUROC: 0,89 vs 0,79
 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
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FibroTest in Histological changes
FT in diagnostic of HBV
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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
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Poynard et al Am J G 2005
Kinetics of fibrosis according to baseline stages in HBV patients
treated with lamivudine 2 years (n=283)
FibroTest
1.00
Conclusion
0.73
0.52
0.75
0.50
F2F3F4 P=0.01
0.25
F0F1 NS
0.00
Baseline
6 mo
12 mo
- 44 Cirrhosis: 42 (95%)
improvement at 24
months
- Significant regression
(>0.30) in 14/44 (32%)
24 mo
FT in diagnostic of HBV
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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 moderatesevere 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
Poynard et al, AASLD 2007
FT in diagnostic of HBV
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Poynard et al, AASLD 2007 - Results
• FibroTest and Fibrosis Stages
Ishak Stages
METAVIR stage
FT in diagnostic of HBV
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Poynard et al, AASLD 2007 - Results
• ActiTest and Necro-Inflammatory Features
Peri Portal Necrosis
Knodell Score
Lobular necrosis
Knodell Score
FT in diagnostic of HBV
Portal Inflammation
Knodell Score
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Poynard et al, AASLD 2007 - Results
• ActiTest and Necro-Inflammatory Scoring System
Ishak Activity grade
METAVIR Activity grade
FT in diagnostic of HBV
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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
1,7800 1,8000
,4400
Baseline
FibroTest
P<0.0001
,4500
,4200
,4000
1,5800
48 weeks
1,4100
P<0.0001
Adefovir
Placebo
Placebo
Adefovir
Baseline
FT in diagnostic of HBV
48 weeks
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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)
FibroTest
Biopsy
P<0.0001
,7000
,5800
P<0.0001
Baseline
48 weeks
2,4400
2,4400
P=0.02
,6500
Baseline
48 weeks
,4500
1,9300
1,6300
Adefovir Biopsy
Placebo Biopsy
Adefovir FibroTest
FT in diagnostic of HBV
Placebo FibroTest
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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 FTAT is 10% (34% of 29%)
Conclusions
 Provides an accurate quantitative estimate of liver fibrosis and necroinflammatory activity
 Is effective and very sensitive as noninvasive marker of histological
changes during treatment or followup without treatment
FT in diagnostic of HBV
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Combination and comparison
with other non invasive methods
FibroScan, APRI, Mp3
FT in diagnostic of HBV
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Sebastiani et al, J Hepatol 2006
• Diagnostic performance of non-invasive biomarkers of liver
fibrosis in chronic hepatitis B (n=110)
Results
HEPATITIS B
(AUC)
APRI
FIBROTEST
 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
>F2
F4
0.72
0.64
0.85
0.76
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
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Sebastiani et al, J Hepatol 2006
– Safe Biopsy
• Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY)
Stepwise modelling aimed to achive accuracy> 95%
APRI
APRI
No Fibrosis
(low accuracy)
Significant fibrosis
(high accuracy)
Unclassified
No cirrhosis
(high accuracy)
FIBROTEST
FIBROTEST
F0-F1
(low accuracy)
Cirrhosis
(low accuracy)
Unclassified
F2-F3-F4
(high accuracy)
F0-F1
(high accuracy)
F2-F3 (low
accuracy)
F4
(high accuracy)
Liver biopsy needed
Liver biopsy needed
>94% accuracy
Liver biopsy not needed
>95% accuracy Liver
biopsy not needed
For significant fibrosis
For cirrhosis
FT in diagnostic of HBV
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Sebastiani et al, J Hepatol 2006
– Safe Biopsy
• Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY)
INTERIM ANALYSIS ON 210 HBV CASES
SAFE BIOPSY for
SAFE BIOPSY for
CIRRHOSIS
SIGNIFICANT FIBROSIS
Accuracy (%)
96
90
Saved biopsies
(%)
Saved cost (%)
45
77
44
75
FT in diagnostic of HBV
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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
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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
0.82
0.81
0.81
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
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
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Meta analysis
FT in diagnostic of HBV
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Poynard 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
FT in diagnostic of HBV
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