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