26 janv. 2012                             Measurement of Fibrosis       Serum markers of fibrosis: improvement of methods  ...
26 janv. 2012     But: Savoir répondre à ce QCM:                                      2jeudi 26 janvier 2012
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012                                       Nash                 Viral necrosis                         Alcohol   ...
26 janv. 2012 Too many subjects at risk of chronic liver disease (1.5 billions)                        Serious adverse eve...
26 janv. 2012     FibroMAX: HCV-HBV-ALD-NAFLD                         5jeudi 26 janvier 2012
26 janv. 2012     FibroMAX: HCV-HBV-ALD-NAFLD                                    NashTest                   ActiTest      ...
26 janv. 2012                        Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
26 janv. 2012                    In Situ                              Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
26 janv. 2012                    In Situ             In Serum: FibroTest                              Imbert-Bismut, Lance...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012                    In Situ                In Serum: FibroTest                  Liver Injury                 ...
26 janv. 2012     Rational of FibroTest:                        Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010j...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:            key protein for Collagenase metabolism   ...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:              key protein for Collagenase metabolism ...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:               key protein for Collagenase metabolism...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:               key protein for Collagenase metabolism...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:               key protein for Collagenase metabolism...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:               key protein for Collagenase metabolism...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:               key protein for Collagenase metabolism...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:                key protein for Collagenase metabolis...
26 janv. 2012     Rational of FibroTest:     • Alpha 2 macroglobulin:                key protein for Collagenase metabolis...
26 janv. 2012      In Situ events: Fibrosis and serum ApoA1 decrease                                                      ...
26 janv. 2012                   Haptoglobin   Hemopexinjeudi 26 janvier 2012
26 janv. 2012                   Haptoglobin   Hemopexinjeudi 26 janvier 2012
26 janv. 2012  Fibrosis biomarkers: 20 years history                                          SJG 2008jeudi 26 janvier 2012
26 janv. 2012  Fibrosis biomarkers: 20 years history                                          SJG 2008                    ...
26 janv. 2012  Fibrosis biomarkers: 20 years history                                          SJG 2008                    ...
26 janv. 2012  Fibrosis biomarkers: 20 years history                                          Poynard SJG 2008jeudi 26 jan...
26 janv. 2012Period 1: 1991-2004 OptimisticLooking for a fibrosis biomarker with accuracy > 90%jeudi 26 janvier 2012
26 janv. 2012                            Biopsy                               =                         Gold Standard     ...
26 janv. 2012                            Biopsy                               =                        0% False Positive  ...
26 janv. 2012                         Liver                        Injury     Serum biomarker             Imaging biomarke...
26 janv. 2012                         Liver                        Injury     Serum biomarker             Imaging biomarke...
Fibrotic Liver                                                Disease        FibroTest OK        AUROC >80%               ...
26 janv. 2012     Period 2: 2005-2009: Sceptic     Standard statistical methods were inappropriatejeudi 26 janvier 2012
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard                             1...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
26 janv. 2012     7 Key methodological issues:     Biopsy is no more a perfect gold standard• Sampling error 		     	   	 ...
Sampling error:             AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length                                ...
Sampling error:             AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length                                ...
Sampling error:             AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length   AUROC 15 mm = 0.82   AUROC 25...
Sampling error:             AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length   AUROC 15 mm = 0.82   AUROC 25...
26 janv. 2012                               Inter-Observers variability:    Biopsy has lower inter-observers concordance f...
26 janv. 2012     Discordances studies: independent endpoints     • 537 prospective cases     • 154 (29%) discordances Fib...
26 janv. 2012     Meta-analysis of prognostic studies: 6 publications and 21 assessments     FibroTest (4 studies, 2396 pa...
Meta-analysis of the prognostic value of biomarkers vs biopsy                                      Survival without liver ...
5 years prognostic value in chronic hepatitis C                  Liver stiffness      FibroTest                           ...
26 janv. 2012     3/7 key methodological issues not well understood     Biopsy is no more a perfect gold standard• Samplin...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
DANA=Difference between Advanced and non-advanced fibrosis stages                                      Fibrotic Liver      ...
26 janv. 2012     Hazardous Tables due to Spectrum Effect (1)                    *Sebastiani CCLM 2011, Bedossa Hepatology...
26 janv. 2012     Hazardous Tables due to Spectrum Effect (1)                Interpretation of Area Under ROC Curves      ...
26 janv. 2012     Hazardous Tables due to Spectrum Effect (1)                Interpretation of Area Under ROC Curves      ...
26 janv. 2012     Hazardous Tables due to Spectrum Effect (1)                Interpretation of Area Under ROC Curves      ...
26 janv. 2012     Hazardous Tables due to Spectrum Effect (1)                Interpretation of Area Under ROC Curves      ...
Using 25 mm liver biopsy a perfect market cannot be validated                                                             ...
26 janv. 2012     Exceeding limits of biopsy:     >90% accuracy is impossible for advanced fibrosis      Comparison of 8 di...
26 janv. 2012Misleading presentation using biopsy as Gold-Standard                              Boursier Hepatology 2012je...
26 janv. 2012Misleading presentation using biopsy as Gold-Standard            Mathematically impossible with biopsy as «Go...
26 janv. 2012     Review of tests by Gebo, Hepatology 2002               « These panels of tests may have the greatest    ...
FibroTest/FibroSure has a Gray Zonejeudi 26 janvier 2012
Biopsy has a Gray Zonejeudi 26 janvier 2012
jeudi 26 janvier 2012
26 janv. 2012     Review of tests by Nguyen, Hepatology 2011                            37jeudi 26 janvier 2012
26 janv. 2012  The gray zone of liver biopsy (1)                               Inter-Observers variability:    Biopsy has ...
26 janv. 2012     Liver Biopsy Analysis Has a Low Level of     Performance for Diagnosis of Intermediate     Stages of Fib...
26 janv. 2012The gray zone of liver biopsy: 27,864 virtual biopsies                              Poynard Clin Gastro Hepat...
The gray zone of liver biopsy: 27,864 virtual biopsies                                   Poynard Clin Gastro Hepatol 2012j...
The gray zone of FibroTest: 6,500 patients with biopsy                                  Poynard Clin Gastro Hepatol 2012je...
Lower gray zone of FibroTest relative to biopsy                                                       Biopsy              ...
26 janv. 2012                        Biopsy is no more a perfect gold standard          FibroTest and Elastography have si...
26 janv. 2012     Period 3: 2010-----     Welcome in a world without perfect Gold Standardjeudi 26 janvier 2012
26 janv. 2012                         Truth in the                         Absence of                        Gold Standard...
26 janv. 2012    Area of fibrosis estimated by biopsy according to its length (mm) in subjects    scoring METAVIR F0 (no fib...
26 janv. 2012    Area of fibrosis estimated by biopsy according to its length (mm) in subjects    scoring METAVIR F0 (no fib...
26 janv. 2012                          5-30 mm Biopsy              FibroTest                              FibroScan       ...
26 janv. 2012     Distribution of 1893 subjects according to the 16 possible combinations of     the 4 tests results: pres...
26 janv. 2012     Distribution of 1893 subjects according to the 16 possible combinations of     the 4 tests results: pres...
26 janv. 2012     Performance for Advanced Fibrosis: Sensitivity                        FibroTest Se               LSM Se ...
26 janv. 2012     Performance for Advanced Fibrosis: Sensitivity                        FibroTest Se                   LSM...
26 janv. 2012     Performance for Advanced Fibrosis: Specificity                        FibroTest Sp               LSM Sp  ...
26 janv. 2012     Performance for Advanced Fibrosis: Specificity                        FibroTest Sp                 LSM Sp...
26 janv. 2012     Performance for Cirrhosis: Sensitivity                         FibroTest Se               LSM Se        ...
26 janv. 2012     Performance for Cirrhosis: Specificity                          FibroTest Sp                   LSM Sp    ...
26 janv. 2012     Biopsy vs Serum marker     Main advantages/disadvantages                         Serum Marker           ...
Geno-FibroTest                               GP                FibroScan                           Hepatologist           ...
FibroTest             ActiTest                          Prevalence                                    A la Parisienne     ...
Elasto-FibroTest               FibroTest                          FibroScan    Serum biomarker                           I...
26 janv. 2012     Elasto-FibroTest® • 1289 patients with CHC and 604 healthy volunteers • Appropriate methods       • Obuc...
26 janv. 2012     Elasto-FibroTest®       • For the diagnosis of cirrhosis Elasto-FibroTest         has significantly highe...
26 janv. 2012     FibroTest validation in “difficult to diagnose patients”     • HIV-HCV: 	         Myers 2003, Cacoub 2008...
26 janv. 2012                   ActiTest vs ALT accuracy for the diagnosis                of necro-Inflammatory histologica...
26 janv. 2012                   ActiTest vs ALT accuracy for the diagnosis                of necro-Inflammatory histologica...
26 janv. 2012                   ActiTest vs ALT accuracy for the diagnosis                of necro-Inflammatory histologica...
26 janv. 2012                   ActiTest vs ALT accuracy for the diagnosis                of necro-Inflammatory histologica...
26 janv. 2012                   ActiTest vs ALT accuracy for the diagnosis                of necro-Inflammatory histologica...
FibroTest Global Quality Estimates                         High Risk                   High Risk                  False Po...
Benefit/Risk must be evaluated for each change in the formula:     It takes time for one stable formula: the example of 360...
One Test, One formula     360,000 FibroTest for Quality Control                        Risk of False positive/negative of ...
26 janv. 2012   3 major pitfalls of Fibrometers’ family     1. Transaminases in a fibrosis biomarker                  • Too...
26 janv. 2012     Which Fibrometer for patients with Hepatitis C ?     Too many variants = Risk of false positive         ...
jeudi 26 janvier 2012
26 janv. 2012     Elastography     • 11 Published studies     • n=2,260     • Standardized AUROC     • Advanced Fibrosis  ...
26 janv. 2012                        Oliveri WJG 2008jeudi 26 janvier 2012
26 janv. 2012                            Pitfalls of Fibroscan                 3.1% Failures and Unreliable results 15.8%j...
26 janv. 2012                                                              Choice of FibroScan Cutoffs    F4 0.73         ...
26 janv. 2012   HCV n=92   Mean Fibrotest and Actitest                 Baseline               12 weeks   24 weeks         ...
26 janv. 2012     HCV n=416     Median % changes Fibrosis estimates (12-24 month)                                     Fibr...
26 janv. 2012     HCV n=416     Mean FibroTest (range 0.00-1.00)                        Baseline              12mo/EOT    ...
26 janv. 2012   HCV n=416   Mean Liver Stiffness Measurements (range 0-75 kPa )                        Baseline           ...
HCV Geno-FibroTest                                                                                                Ref #123...
26 janv. 2012     HCV-GenoFibroTest: Liver injury, Virus Resistance, Host     Genes for treatment Response and Tolerance  ...
26 janv. 2012     Conclusion for Biomarkers (1) • Accept than a 25 mm biopsy can have 25% false positive/negative and that...
26 janv. 2012     Conclusion for Biomarkers (2)       • Finally guidelines for the indications of fibrosis tests         sh...
26 janv. 2012     Summary: Responses to Questionsjeudi 26 janvier 2012
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?jeudi 26 janvier 2012
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?       • No as 25 mm has 25%...
26 janv. 2012     Summary: Responses to Questionsjeudi 26 janvier 2012
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?jeudi 26 janvier 2...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Summary: Responses to Questions • Performance of Fibrotest according to liver disease?       • Similar d...
26 janv. 2012     Anticipated Frequently Asked Questionsjeudi 26 janvier 2012
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of inter...
26 janv. 2012     But: Savoir répondre à ce QCM:                                      84jeudi 26 janvier 2012
26 janv. 2012     But: Savoir répondre à ce QCM:         Parmi les 5 propositions suivantes concernant les performances re...
26 janv. 2012     But: Savoir répondre à ce QCM:          Parmi les 5 propositions suivantes concernant les performances r...
26 janv. 2012     But: Savoir répondre à ce QCM:          Parmi les 5 propositions suivantes concernant les performances r...
26 janv. 2012     But: Savoir répondre à ce QCM:          Parmi les 5 propositions suivantes concernant les performances r...
26 janv. 2012     But: Savoir répondre à ce QCM:          Parmi les 5 propositions suivantes concernant les performances r...
26 janv. 2012     But: Savoir répondre à ce QCM:          Parmi les 5 propositions suivantes concernant les performances r...
Du 2012 tp biomarkers
Du 2012 tp biomarkers
Du 2012 tp biomarkers
Du 2012 tp biomarkers
Du 2012 tp biomarkers
Du 2012 tp biomarkers
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Du 2012 tp biomarkers

  1. 1. 26 janv. 2012 Measurement of Fibrosis Serum markers of fibrosis: improvement of methods Truth without A Gold Standard Thierry Poynard + AP-HP Groupe Hospitalier Pitié Salpêtrière, UPMC Liver Center, Université Paris 6, INSERM U680, Biopredictive France LiverCenterjeudi 26 janvier 2012
  2. 2. 26 janv. 2012 But: Savoir répondre à ce QCM: 2jeudi 26 janvier 2012
  3. 3. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 2jeudi 26 janvier 2012
  4. 4. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 2jeudi 26 janvier 2012
  5. 5. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 2jeudi 26 janvier 2012
  6. 6. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 3. Une biopsie de 25 mm peut avoir des faux négatifs pour le diagnostic de fibrose avancée (stades F2F3F4) mais très rarement des faux positifs. 2jeudi 26 janvier 2012
  7. 7. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 3. Une biopsie de 25 mm peut avoir des faux négatifs pour le diagnostic de fibrose avancée (stades F2F3F4) mais très rarement des faux positifs. 4. Le FibroTest a une meilleure valeur diagnostique pour le stade de cirrhose (F4) que pour le stade intermédiaire F2 2jeudi 26 janvier 2012
  8. 8. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont vraies ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 3. Une biopsie de 25 mm peut avoir des faux négatifs pour le diagnostic de fibrose avancée (stades F2F3F4) mais très rarement des faux positifs. 4. Le FibroTest a une meilleure valeur diagnostique pour le stade de cirrhose (F4) que pour le stade intermédiaire F2 5. Pour une bonne estimation des performance d’un test il faut calculer les valeurs diagnostiques non seulement pour le diagnostic de cirrhose (F4) vs F0/F1/F2/F), mais aussi pour le diagnostic de F3/F4 vs F2/F1/F0, F2/F3/F4 vs F0/F1, et F1/F2/F3/F4 vs F0. 2jeudi 26 janvier 2012
  9. 9. 26 janv. 2012 Nash Viral necrosis Alcohol Activity Ash Liver Injury Fibrosis Steatosisjeudi 26 janvier 2012
  10. 10. 26 janv. 2012 Too many subjects at risk of chronic liver disease (1.5 billions) Serious adverse events of biopsy Non-invasive alternatives to biopsy for stagingjeudi 26 janvier 2012
  11. 11. 26 janv. 2012 FibroMAX: HCV-HBV-ALD-NAFLD 5jeudi 26 janvier 2012
  12. 12. 26 janv. 2012 FibroMAX: HCV-HBV-ALD-NAFLD NashTest ActiTest AshTest FibroMAX FibroTest SteatoTest 5jeudi 26 janvier 2012
  13. 13. 26 janv. 2012 Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  14. 14. 26 janv. 2012 In Situ Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  15. 15. 26 janv. 2012 In Situ In Serum: FibroTest Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  16. 16. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Fibrotic Matrix Activated Stellate Cells Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  17. 17. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Fibrotic Matrix Activated Stellate Cells Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  18. 18. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Fibrotic Matrix Activated Stellate Cells Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  19. 19. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Fibrotic Matrix Activated Stellate Cells Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  20. 20. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Fibrotic Matrix Activated Stellate Cells Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  21. 21. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Fibrotic Matrix Activated Stellate Cells Haptoglobin Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  22. 22. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Apolipoprotein A1 Fibrotic Matrix Activated Stellate Cells Haptoglobin Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  23. 23. 26 janv. 2012 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Apolipoprotein A1 Fibrotic Matrix Activated Stellate Cells Haptoglobin Imbert-Bismut, Lancet 2001jeudi 26 janvier 2012
  24. 24. 26 janv. 2012 Rational of FibroTest: Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  25. 25. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  26. 26. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  27. 27. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  28. 28. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  29. 29. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis • Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  30. 30. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis • Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis • No transaminases: to prevent inflammatory necrosis confusion (ActiTest) Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  31. 31. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis • Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis • No transaminases: to prevent inflammatory necrosis confusion (ActiTest) • Proteomic has blindly proved the major diagnostic value of Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  32. 32. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis • Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis • No transaminases: to prevent inflammatory necrosis confusion (ActiTest) • Proteomic has blindly proved the major diagnostic value of • Apolipoprotein A, A2M Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  33. 33. 26 janv. 2012 Rational of FibroTest: • Alpha 2 macroglobulin: key protein for Collagenase metabolism • Apolipoprotein A1 key protein for Collagen trapping • Haptoglobin: key protein for binding Free Hemoglobin oxidant • Total Bilirubin: specific marker of severe late Fibrosis • Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis • No transaminases: to prevent inflammatory necrosis confusion (ActiTest) • Proteomic has blindly proved the major diagnostic value of • Apolipoprotein A, A2M • Haptoglobin Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010jeudi 26 janvier 2012
  34. 34. 26 janv. 2012 In Situ events: Fibrosis and serum ApoA1 decrease Trapping Apo A1 Down Regulation Paradis Cell Mol Biol 1996, Paradis Hepatology 1996, Mathurin Hepatology 1996.jeudi 26 janvier 2012
  35. 35. 26 janv. 2012 Haptoglobin Hemopexinjeudi 26 janvier 2012
  36. 36. 26 janv. 2012 Haptoglobin Hemopexinjeudi 26 janvier 2012
  37. 37. 26 janv. 2012 Fibrosis biomarkers: 20 years history SJG 2008jeudi 26 janvier 2012
  38. 38. 26 janv. 2012 Fibrosis biomarkers: 20 years history SJG 2008 n=100jeudi 26 janvier 2012
  39. 39. 26 janv. 2012 Fibrosis biomarkers: 20 years history SJG 2008 n=100 n=600,000jeudi 26 janvier 2012
  40. 40. 26 janv. 2012 Fibrosis biomarkers: 20 years history Poynard SJG 2008jeudi 26 janvier 2012
  41. 41. 26 janv. 2012Period 1: 1991-2004 OptimisticLooking for a fibrosis biomarker with accuracy > 90%jeudi 26 janvier 2012
  42. 42. 26 janv. 2012 Biopsy = Gold Standard Biopsy = 0% False Positive 0% False Negativejeudi 26 janvier 2012
  43. 43. 26 janv. 2012 Biopsy = 0% False Positive 0% False Negativejeudi 26 janvier 2012
  44. 44. 26 janv. 2012 Liver Injury Serum biomarker Imaging biomarkerjeudi 26 janvier 2012
  45. 45. 26 janv. 2012 Liver Injury Serum biomarker Imaging biomarkerjeudi 26 janvier 2012
  46. 46. Fibrotic Liver Disease FibroTest OK AUROC >80% F0 F1 «Gray Zone»: Biopsy F2 F3 FibroTest OK F4 FibroScan OK AUROC >80% Hemorrhage Liver failure Cancer Imbert Bismut 2001, Castera 2005jeudi 26 janvier 2012
  47. 47. 26 janv. 2012 Period 2: 2005-2009: Sceptic Standard statistical methods were inappropriatejeudi 26 janvier 2012
  48. 48. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard 18jeudi 26 janvier 2012
  49. 49. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003 18jeudi 26 janvier 2012
  50. 50. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005 18jeudi 26 janvier 2012
  51. 51. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006 18jeudi 26 janvier 2012
  52. 52. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006• Prognostic studies Ngo 2006, Vergniol 2011 18jeudi 26 janvier 2012
  53. 53. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006• Prognostic studies Ngo 2006, Vergniol 2011• Spectrum effect Poynard 2007, Lambert 2008 18jeudi 26 janvier 2012
  54. 54. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006• Prognostic studies Ngo 2006, Vergniol 2011• Spectrum effect Poynard 2007, Lambert 2008• Exceeding limits of biopsy Metha 2009 18jeudi 26 janvier 2012
  55. 55. 26 janv. 2012 7 Key methodological issues: Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006• Prognostic studies Ngo 2006, Vergniol 2011• Spectrum effect Poynard 2007, Lambert 2008• Exceeding limits of biopsy Metha 2009• Biopsy has a gray zone Poynard 2012 18jeudi 26 janvier 2012
  56. 56. Sampling error: AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length Bedossa Hepatology 2003jeudi 26 janvier 2012
  57. 57. Sampling error: AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length Bedossa Hepatology 2003jeudi 26 janvier 2012
  58. 58. Sampling error: AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length AUROC 15 mm = 0.82 AUROC 25 mm = 0.89 Bedossa Hepatology 2003jeudi 26 janvier 2012
  59. 59. Sampling error: AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length AUROC 15 mm = 0.82 AUROC 25 mm = 0.89«We showed that with 25-mmlong biopsy specimens, only75% were scored correctly» Bedossa Hepatology 2003jeudi 26 janvier 2012
  60. 60. 26 janv. 2012 Inter-Observers variability: Biopsy has lower inter-observers concordance for intermediate stages F0 F1 F2 F3 F4 0,90 0,87 0,60 0,52 0,39 0,38 0,35 0,30 0 Kappa Rousselet, Hepatology 2005jeudi 26 janvier 2012
  61. 61. 26 janv. 2012 Discordances studies: independent endpoints • 537 prospective cases • 154 (29%) discordances FibroTest/Biopsy • Error attributable • To FibroTest: 2% • To Biopsy: 18% Poynard Clin Chem 2004, Halfon AJG 2006 21jeudi 26 janvier 2012
  62. 62. 26 janv. 2012 Meta-analysis of prognostic studies: 6 publications and 21 assessments FibroTest (4 studies, 2396 patients), APRI (5 studies, 2422 patients), FIB4 (3 studies,1184 patients) First author, year Disease Biomarker assessed with area under the ROC curve Ngo, 2006 HCV FibroTest, APRI, Biopsy Ngo, 2008 HBV FibroTest, APRI, Biopsy Naveau, 2009 ALD FibroTest, APRI, FIB4, HepaScore, FibroMeter, Biopsy Nunes, 2010 HCV APRI, FIB4 Parkes, 2010 Mixed ELF, Biopsy Vergniol, 2011 HCV FibroTest, APRI, FibroScan, FIB4, Biopsy Poynard Gastroenterol Hepatol 2011jeudi 26 janvier 2012
  63. 63. Meta-analysis of the prognostic value of biomarkers vs biopsy Survival without liver deaths Only FibroTest has same prognostic value than biopsy Poynard Gastroenterol Hepatol 2011jeudi 26 janvier 2012
  64. 64. 5 years prognostic value in chronic hepatitis C Liver stiffness FibroTest Vergniol Gastroenterology 2011jeudi 26 janvier 2012
  65. 65. 26 janv. 2012 3/7 key methodological issues not well understood Biopsy is no more a perfect gold standard• Sampling error Bedossa 2003• Inter-observers variability Rousselet 2005• Discordance studies Poynard 2004, Halfon 2006• Prognostic studies Ngo 2006, Vergniol 2011• Spectrum effect Poynard 2007, Lambert 2008• Exceeding limits of biopsy Metha 2009• Biopsy has a gray zone Poynard 2012 25jeudi 26 janvier 2012
  66. 66. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Black and White Spectrum F1 F2 FibroTest AUROC=0.98 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  67. 67. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Black and White Spectrum F1 F2 FibroTest AUROC=0.98 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  68. 68. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Black and White Spectrum F1 F2 FibroTest AUROC=0.98 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  69. 69. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Black and White Spectrum F1 DANA=4 F2 FibroTest AUROC=0.98 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  70. 70. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Gray Spectrum F1 F2 FibroTest AUROC=0.67 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  71. 71. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Gray Spectrum F1 F2 FibroTest AUROC=0.67 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  72. 72. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Gray Spectrum F1 F2 FibroTest AUROC=0.67 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  73. 73. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Gray Spectrum F1 DANA=1 F2 FibroTest AUROC=0.67 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  74. 74. DANA=Difference between Advanced and non-advanced fibrosis stages Fibrotic Liver Disease F0 Standard Spectrum F1 DANA=2.5 F2 FibroTest AUROC=0.85 F3 F4Obuchowski measure=AUROCs Pair-wise comparison between all stagesjeudi 26 janvier 2012
  75. 75. 26 janv. 2012 Hazardous Tables due to Spectrum Effect (1) *Sebastiani CCLM 2011, Bedossa Hepatology 2003, Poynard Clin Chem 2007jeudi 26 janvier 2012
  76. 76. 26 janv. 2012 Hazardous Tables due to Spectrum Effect (1) Interpretation of Area Under ROC Curves AUROC Score* Biopsy FibroTest 0.90-1 Excellent F0 vs F4 0.80-0.90 Good 25 mm F1 vs F2 F01 vs F234 0.70-0.80 Fair 5 mm F1 vs F2 F0 vs F2 0.60-0.70 Poor 5 mm F0 vs F1 F1 vs F2 0.50-0.60 Fail *Sebastiani CCLM 2011, Bedossa Hepatology 2003, Poynard Clin Chem 2007jeudi 26 janvier 2012
  77. 77. 26 janv. 2012 Hazardous Tables due to Spectrum Effect (1) Interpretation of Area Under ROC Curves AUROC Score* Biopsy FibroTest 0.90-1 Excellent F0 vs F4 0.80-0.90 Good 25 mm F1 vs F2 F01 vs F234 0.70-0.80 Fair 5 mm F1 vs F2 F0 vs F2 0.60-0.70 Poor 5 mm F0 vs F1 F1 vs F2 0.50-0.60 Fail *Sebastiani CCLM 2011, Bedossa Hepatology 2003, Poynard Clin Chem 2007jeudi 26 janvier 2012
  78. 78. 26 janv. 2012 Hazardous Tables due to Spectrum Effect (1) Interpretation of Area Under ROC Curves AUROC Score* Biopsy FibroTest 0.90-1 Excellent F0 vs F4 0.80-0.90 Good 25 mm F1 vs F2 F01 vs F234 0.70-0.80 Fair 5 mm F1 vs F2 F0 vs F2 0.60-0.70 Poor 5 mm F0 vs F1 F1 vs F2 0.50-0.60 Fail *Sebastiani CCLM 2011, Bedossa Hepatology 2003, Poynard Clin Chem 2007jeudi 26 janvier 2012
  79. 79. 26 janv. 2012 Hazardous Tables due to Spectrum Effect (1) Interpretation of Area Under ROC Curves AUROC Score* Biopsy FibroTest 0.90-1 Excellent F0 vs F4 0.80-0.90 Good 25 mm F1 vs F2 F01 vs F234 0.70-0.80 Fair 5 mm F1 vs F2 F0 vs F2 0.60-0.70 Poor 5 mm F0 vs F1 F1 vs F2 0.50-0.60 Fail *Sebastiani CCLM 2011, Bedossa Hepatology 2003, Poynard Clin Chem 2007jeudi 26 janvier 2012
  80. 80. Using 25 mm liver biopsy a perfect market cannot be validated Metha J Hepatol 2009 Black shading represents the set of conditions under which the AUROC values exceed what has already been observedjeudi 26 janvier 2012
  81. 81. 26 janv. 2012 Exceeding limits of biopsy: >90% accuracy is impossible for advanced fibrosis Comparison of 8 diagnostic algorithms for liver fibrosis in hepatitis C: New algorithms are more precise and entirely non-invasive. Boursier et al, Hepatology 2012 31jeudi 26 janvier 2012
  82. 82. 26 janv. 2012Misleading presentation using biopsy as Gold-Standard Boursier Hepatology 2012jeudi 26 janvier 2012
  83. 83. 26 janv. 2012Misleading presentation using biopsy as Gold-Standard Mathematically impossible with biopsy as «Gold Standard Boursier Hepatology 2012jeudi 26 janvier 2012
  84. 84. 26 janv. 2012 Review of tests by Gebo, Hepatology 2002 « These panels of tests may have the greatest value in predicting fibrosis or cirrhosis » «  Biochemical tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis/cirrhosis, and were poor at predicting intermediate levels of fibrosis » 33jeudi 26 janvier 2012
  85. 85. FibroTest/FibroSure has a Gray Zonejeudi 26 janvier 2012
  86. 86. Biopsy has a Gray Zonejeudi 26 janvier 2012
  87. 87. jeudi 26 janvier 2012
  88. 88. 26 janv. 2012 Review of tests by Nguyen, Hepatology 2011 37jeudi 26 janvier 2012
  89. 89. 26 janv. 2012 The gray zone of liver biopsy (1) Inter-Observers variability: Biopsy has lower inter-observers concordance for intermediate stages F0 F1 F2 F3 F4 0,90 0,87 0,60 0,52 0,39 0,38 0,35 0,30 0 Kappa Rousselet, Hepatology 2005jeudi 26 janvier 2012
  90. 90. 26 janv. 2012 Liver Biopsy Analysis Has a Low Level of Performance for Diagnosis of Intermediate Stages of Fibrosis The gray anatomy of 27,869 virtual biopsies and 6,500 patients Poynard Clin Gastro Hepatol 2012 in press Poynard, BMC 2005, J Hepatol 2011jeudi 26 janvier 2012
  91. 91. 26 janv. 2012The gray zone of liver biopsy: 27,864 virtual biopsies Poynard Clin Gastro Hepatol 2012jeudi 26 janvier 2012
  92. 92. The gray zone of liver biopsy: 27,864 virtual biopsies Poynard Clin Gastro Hepatol 2012jeudi 26 janvier 2012
  93. 93. The gray zone of FibroTest: 6,500 patients with biopsy Poynard Clin Gastro Hepatol 2012jeudi 26 janvier 2012
  94. 94. Lower gray zone of FibroTest relative to biopsy Biopsy TexteDecrease FibroTest F2vsF1 58% lower compared with F1vsF0 41% lower compared with 4vsF3. Fibrotest Poynard Clin Gastro Hepatol 2012jeudi 26 janvier 2012
  95. 95. 26 janv. 2012 Biopsy is no more a perfect gold standard FibroTest and Elastography have similar performance 2006: Approval Markers French Health Authorities HCV 2011: Guidelines EASL 2011jeudi 26 janvier 2012
  96. 96. 26 janv. 2012 Period 3: 2010----- Welcome in a world without perfect Gold Standardjeudi 26 janvier 2012
  97. 97. 26 janv. 2012 Truth in the Absence of Gold Standard 25 mm Biopsy 25% False Positive False Negativejeudi 26 janvier 2012
  98. 98. 26 janv. 2012 Area of fibrosis estimated by biopsy according to its length (mm) in subjects scoring METAVIR F0 (no fibrosis) on large surgical section. Poynard J Hepatol 2012jeudi 26 janvier 2012
  99. 99. 26 janv. 2012 Area of fibrosis estimated by biopsy according to its length (mm) in subjects scoring METAVIR F0 (no fibrosis) on large surgical section. Cirrhosis Advanced fibrosisArea of fibrosis >5.3%: 16.3% false positives 20mm biopsy for diagnosis of advanced fibrosis >16.5%: 0.3% false positives 20mm biopsy for diagnosis of cirrhosis. Poynard J Hepatol 2012jeudi 26 janvier 2012
  100. 100. 26 janv. 2012 5-30 mm Biopsy FibroTest FibroScan Truth ALT Poynard J Hepatol 2011jeudi 26 janvier 2012
  101. 101. 26 janv. 2012 Distribution of 1893 subjects according to the 16 possible combinations of the 4 tests results: presumed advanced fibrosis (present=1) or not (=0) 16 combinations of 4 tests results Number of subjects FibroTest LSM ALT Biopsy Observed Expected by model 0 0 0 0 621 615.5 0 0 0 1 186 191.1 0 0 1 0 190 197.5 0 0 1 1 123 117.4 0 1 0 0 10 10.0 0 1 0 1 18 18.4 0 1 1 0 18 16.4 0 1 1 1 39 39.2 1 0 0 0 41 47.0 1 0 0 1 58 54.8 1 0 1 0 95 86.6 1 0 1 1 141 145.1 1 1 0 0 9 8.3 1 1 0 1 45 43.1 1 1 1 0 23 25.7 1 1 1 1 276 277.0 Poynard, J Hepatol 2011jeudi 26 janvier 2012
  102. 102. 26 janv. 2012 Distribution of 1893 subjects according to the 16 possible combinations of the 4 tests results: presumed advanced fibrosis (present=1) or not (=0) 16 combinations of 4 tests results Number of subjects Expected FibroTest LSM ALT Biopsy Observed by model 0 0 0 0 621 615.5 0 0 0 1 186 191.1 ... 1 1 1 1 276 277.0 Poynard, J Hepatol 2011jeudi 26 janvier 2012
  103. 103. 26 janv. 2012 Performance for Advanced Fibrosis: Sensitivity FibroTest Se LSM Se Biopsie Se The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness Poynard, J Hepatol 2011jeudi 26 janvier 2012
  104. 104. 26 janv. 2012 Performance for Advanced Fibrosis: Sensitivity FibroTest Se LSM Se Biopsie Se 100% 100% 75% 68% 66% 63% 48% 45% 50% 25% Reference Latent Class 0% Reference Biopsy The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness Poynard, J Hepatol 2011jeudi 26 janvier 2012
  105. 105. 26 janv. 2012 Performance for Advanced Fibrosis: Specificity FibroTest Sp LSM Sp Biopsy Sp The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness Poynard, J Hepatol 2011jeudi 26 janvier 2012
  106. 106. 26 janv. 2012 Performance for Advanced Fibrosis: Specificity FibroTest Sp LSM Sp Biopsy Sp 100% 100% 93% 96% 89% 85% 75% 67% 50% 25% Reference Latent Class 0% Reference Biopsy The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness Poynard, J Hepatol 2011jeudi 26 janvier 2012
  107. 107. 26 janv. 2012 Performance for Cirrhosis: Sensitivity FibroTest Se LSM Se Biopsie Se 100% 100% 75% 68% 65% 51% 50% 41% 39% 25% 0% Reference Latent Class Reference Biopsy The standard cutoffs: 0.74 FibroTest, 14.5 kPa Stiffness Poynard, J Hepatol 2011jeudi 26 janvier 2012
  108. 108. 26 janv. 2012 Performance for Cirrhosis: Specificity FibroTest Sp LSM Sp Biopsy Sp 100% 95% 100% 89% 93% 95% 87% 75% 50% 25% 0% Reference Latent Class Reference Biopsy The standard cutoffs: for cirrhosis 0.74 for FibroTest, and 14.5 kilo-Pascal for stiffness (LSM) Poynard, J Hepatol 2011jeudi 26 janvier 2012
  109. 109. 26 janv. 2012 Biopsy vs Serum marker Main advantages/disadvantages Serum Marker FibroTest Less accurate for No grey zone relatively to intermediate stages biopsy Fibrosis only ActiTest/SteatoTest Delays result proprietary 24-48h tests False positive/hemolysis/ Yes but 0.97% inflammation/Gilbert (3349/345695; 0.94-1.00) Nguyen Hepatology, 2011 Poynard BMC Gastro 2011jeudi 26 janvier 2012
  110. 110. Geno-FibroTest GP FibroScan Hepatologist Epidemiologist Choice Serum biomarker Imaging biomarkerjeudi 26 janvier 2012
  111. 111. FibroTest ActiTest Prevalence A la Parisienne Fibrotest First Line 98% If not interpretable Fibroscan 2% If not interpretable <1% Biopsyjeudi 26 janvier 2012
  112. 112. Elasto-FibroTest FibroTest FibroScan Serum biomarker Imaging biomarkerjeudi 26 janvier 2012
  113. 113. 26 janv. 2012 Elasto-FibroTest® • 1289 patients with CHC and 604 healthy volunteers • Appropriate methods • Obuchowski measures • Methods without Gold Standard Poynard, JFHOD 2012 59jeudi 26 janvier 2012
  114. 114. 26 janv. 2012 Elasto-FibroTest® • For the diagnosis of cirrhosis Elasto-FibroTest has significantly higher performances than FibroTest or Fibroscan alone. • For the diagnosis of advanced fibrosis (F234) no improvement in performance has been observed vs FibroTest alone, when a method without gold standard was used. Poynard, JFHOD 2012 60jeudi 26 janvier 2012
  115. 115. 26 janv. 2012 FibroTest validation in “difficult to diagnose patients” • HIV-HCV: Myers 2003, Cacoub 2008 • Aged patients: Thabut 2006 • Children: de Ledinghen 2007, Friedrich 2008 • Renal insufficiency: Varaud 2005 • Vasculitis: Cacoub 2006 • Hemophiliac Mahor 2006 • Transplanted • Kidney: Varaud 2006 • Liver: Hamelet 2008 • Normal ALT Poynard 2006, 2008, Castera 2006 61jeudi 26 janvier 2012
  116. 116. 26 janv. 2012 ActiTest vs ALT accuracy for the diagnosis of necro-Inflammatory histological activity grade in 1,250 patients with chronic hepatitis C * m (se) One test for all grades pairwise area under the ROC curves comparisonsjeudi 26 janvier 2012
  117. 117. 26 janv. 2012 ActiTest vs ALT accuracy for the diagnosis of necro-Inflammatory histological activity grade in 1,250 patients with chronic hepatitis C ActiTest ALT Significance Obuchowski* Measure 0.848 (0.005) 0.834 (0.006) P= 0.008 * m (se) One test for all grades pairwise area under the ROC curves comparisonsjeudi 26 janvier 2012
  118. 118. 26 janv. 2012 ActiTest vs ALT accuracy for the diagnosis of necro-Inflammatory histological activity grade in 1,250 patients with chronic hepatitis C ActiTest ALT Significance Obuchowski* Measure 0.848 (0.005) 0.834 (0.006) P= 0.008 * m (se) One test for all grades pairwise area under the ROC curves comparisonsjeudi 26 janvier 2012
  119. 119. 26 janv. 2012 ActiTest vs ALT accuracy for the diagnosis of necro-Inflammatory histological activity grade in 1,250 patients with chronic hepatitis C ActiTest ALT Significance Obuchowski* Measure 0.848 (0.005) 0.834 (0.006) P= 0.008 * m (se) One test for all grades pairwise area under the ROC curves comparisonsjeudi 26 janvier 2012
  120. 120. 26 janv. 2012 ActiTest vs ALT accuracy for the diagnosis of necro-Inflammatory histological activity grade in 1,250 patients with chronic hepatitis C ActiTest ALT Significance Obuchowski* Measure 0.848 (0.005) 0.834 (0.006) P= 0.008 * m (se) One test for all grades pairwise area under the ROC curves comparisonsjeudi 26 janvier 2012
  121. 121. FibroTest Global Quality Estimates High Risk High Risk False Positive Negative False Positive Negative 5/954 (0.52%) 38/7494 (0.51%) FibroScan (Roulot et al 2008) >7.1 kPa= 12.6%: False Positives ? High Risk High Risk False Positive Negative False Positive Negative Poynard EASL 2010, Roulot J Hepatol 2008 3349/345,695 (0.97%) 491/24,872 (1.97%)jeudi 26 janvier 2012
  122. 122. Benefit/Risk must be evaluated for each change in the formula: It takes time for one stable formula: the example of 360,000 FibroTest (c) BioPredictive 2008 - All Rights Reserved - No reproduction without written permissionjeudi 26 janvier 2012
  123. 123. One Test, One formula 360,000 FibroTest for Quality Control Risk of False positive/negative of FibroTest • Tertiary center: 1.97% • HIV co-infection: 1.77% • Sub-Saharan origin: 2.61% (c) BioPredictive 2008 - All Rights Reserved - No reproduction without written permissionjeudi 26 janvier 2012
  124. 124. 26 janv. 2012 3 major pitfalls of Fibrometers’ family 1. Transaminases in a fibrosis biomarker • Too rapid decrease of a fibrosis biomarkers is a sign of confounding factor • Need to associate fibrosis biomarker with a specific marker of steatosis (SteatoTest) or activity (ActiTest) 2. Benefit/Risk must be evaluated for each change in the formula of algorithms and there is 8 different formula... 3. The «new» CirrhoMeter is build on the false assumption that biopsy is a gold standard. To use only a test for»Cirrhosis» is less efficient than a quantitative estimate from F0 to F4. When the CirrhoTest is negative you must re-perform another test to see if the patient is F0 or F3.... 66jeudi 26 janvier 2012
  125. 125. 26 janv. 2012 Which Fibrometer for patients with Hepatitis C ? Too many variants = Risk of false positive FibroMeter Variant Year Components FM-1G 2005 PLT, PI, AST, A2M, HA, Urea, Age FM-2G V* 2008 + Gender FM-3G 2008 Switch GGT/HA FM-3G+ (CirrhoMeter) 2009 New formula for cirrhosis FM-HICV 2010 AST, A2M, PI CSF-Index 2011 Combined with LSM SF-Index 2011 Combined with LSM C-Index 2011 Combined with LSM *ONLY one ( FM-2G V) is approved by Haute Autorité de Santé PLT: platelet counts, PI prothrombin index, AST aspartate amino transferase, A2M alpha2 macroglobulin, HA hyaluronic acidjeudi 26 janvier 2012
  126. 126. jeudi 26 janvier 2012
  127. 127. 26 janv. 2012 Elastography • 11 Published studies • n=2,260 • Standardized AUROC • Advanced Fibrosis • 0.89 (0.84-0.95) Friedrich Rust et al Gastroenterology 2008, Poynard et al SJG 2008 69jeudi 26 janvier 2012
  128. 128. 26 janv. 2012 Oliveri WJG 2008jeudi 26 janvier 2012
  129. 129. 26 janv. 2012 Pitfalls of Fibroscan 3.1% Failures and Unreliable results 15.8%jeudi 26 janvier 2012
  130. 130. 26 janv. 2012 Choice of FibroScan Cutoffs F4 0.73 Castera 2005, Ketanneh 2007 Roulot 2008 For F2: 7.1 or 8.8 kPa ? F2 0.48 Patients: false negatives ? Low negative predictive value Healthy volunteers: 7.1 kPa 12.6% false positives ? For screening 7.1 kPa ? For patients 8.8 kPa ? F2 8.8 kPa F4 14.5 kPa No rationale for changing cutoff according to liver disease Poynard PlosOne 2008jeudi 26 janvier 2012
  131. 131. 26 janv. 2012 HCV n=92 Mean Fibrotest and Actitest Baseline 12 weeks 24 weeks 48 weeks Fibrosis Activity 1,00 0,80 0,60 0,40 0,20 Fibrotest 0 Actitest D’Arondel et al JVH 2006jeudi 26 janvier 2012
  132. 132. 26 janv. 2012 HCV n=416 Median % changes Fibrosis estimates (12-24 month) FibroTest Fibroscan 10% 5% 0% -5% -10% -15% -20% -25% Control (n=304) -30% NR (n=27) SVR (n=70) Vergniol et al JVH 2009jeudi 26 janvier 2012
  133. 133. 26 janv. 2012 HCV n=416 Mean FibroTest (range 0.00-1.00) Baseline 12mo/EOT 24mo/EOF Slow decrease = Not related to activity Slow increase = Sensitivity 0,60 0,48 0,36 0,24 0,12 Control (n=304) 0 SVR (n=70) Vergniol et al JVH 2009jeudi 26 janvier 2012
  134. 134. 26 janv. 2012 HCV n=416 Mean Liver Stiffness Measurements (range 0-75 kPa ) Baseline 12mo/EOT 24mo/EOF Too Early = No treatment No increase = necro-inflammatory activity Lack of sensitivity ? improvement ? 15 12 9 6 3 Control (n=304) 0 SVR (n=70) Vergniol et al JVH 2009jeudi 26 janvier 2012
  135. 135. HCV Geno-FibroTest Ref #123456 Internal reference : TEST http://www.biopredictive.com/ Patient Biomarkers Hepatitis C Birth date 1935-09-22 Sample date 2009-05-06 HCV Viral Load 250000 Sex Female Alpha2 3.12 g/l HCV Genotype Genotype 2 Macroglobulin IL28B Genotype C/C Apolipoprotein A1 1.82 g/l Bilirubin 13.00 Ämol/l Haptoglobin 1.18 g/l Gamma GT 149.00 IU/l ALT 47.00 IU/l Tests results FibroTest ActiTest HCV Geno-FibroTest FibroTest assesses the ActiTest assesses activity Chance of sustained fibrosis of the liver (inflammation in chronic virological response. viral hepatitis C or B) Score: 0.72 Score: 0.41 Score: 0.14 (F3) (A1-A2) (SVR ++) F3: advanced fibrosis A1-A2: minimal activity SVR ++: very good response Precautions of use and interpretability Å The reliability of results is dependent on compliance with the preanalytical and analytical conditions recommended by BioPredictive. Å The Tests have to be deferred for: acute hemolysis, acute hepatitis, acute inflammation, extra hepatic cholestasis. Å The advice of a specialist should be sought for interpretation in chronic hemolysis and Gilberts syndrome. Å The Test interpretation is not validated in liver transplant patients. Å Isolated extreme values of one of the components should lead to caution in interpreting the results. Å In case of discordance between a biopsy result and a Test, it is recommended to seek the advice of a specialist. The causes of these discordances could be due to a flaw of the Test or to a flaw in the biopsy: i.e. a liver biopsy has a 33% variability rate for one fibrosis stage Å FibroTest is interpretable for chronic hepatitis B and C, alcoholic and non alcoholic steatosis. Å ActiTest is interpretable for chronic hepatitis B and C. Å HCV Geno-FibroTest is interpretable when FibroTest is interpretable and when the IL28b genotype is interpretable. C/C : good response, C/T : intermediate response, T/T : poor response.jeudi 26 janvier 2012
  136. 136. 26 janv. 2012 HCV-GenoFibroTest: Liver injury, Virus Resistance, Host Genes for treatment Response and Tolerance Genotype Viral Load IL28B Viral Resistance ITPA HCV- ActiTest GenoFibroTest UGT1A1 FibroTest SteatoTest 78jeudi 26 janvier 2012
  137. 137. 26 janv. 2012 Conclusion for Biomarkers (1) • Accept than a 25 mm biopsy can have 25% false positive/negative and that the risk of biopsys error is greater between stage F2vsF1 than for the extreme stages F1vsF0 and F4vsF3. • Dont use non-Evidence Based statements: • «Gray Zone for intermediate stages» • «Percentage of biopsies avoided» • Avoid the presentation of sAUROCs of multiple stages combinations in a Table (i.e. F4vsF2F3F4; F4F3vsF2F1F0; F4F3F2vsF1F0) to prevent the spectrum effect. • Apply appropriate methods: • Obuchowski measures • Methods without Gold Standard 79jeudi 26 janvier 2012
  138. 138. 26 janv. 2012 Conclusion for Biomarkers (2) • Finally guidelines for the indications of fibrosis tests should take into consideration these evidence-based data. • At least for FibroTest there is no scientific reason for recommending a biopsy for the diagnosis of intermediate fibrosis stages. 80jeudi 26 janvier 2012
  139. 139. 26 janv. 2012 Summary: Responses to Questionsjeudi 26 janvier 2012
  140. 140. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible?jeudi 26 janvier 2012
  141. 141. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/Njeudi 26 janvier 2012
  142. 142. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages?jeudi 26 janvier 2012
  143. 143. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages? • No as this is the same for 25 mm biopsy (Spectrum effect)jeudi 26 janvier 2012
  144. 144. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages? • No as this is the same for 25 mm biopsy (Spectrum effect) • Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI...jeudi 26 janvier 2012
  145. 145. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages? • No as this is the same for 25 mm biopsy (Spectrum effect) • Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI... • Yes higher performance and safety than ALT, Forns, APRIjeudi 26 janvier 2012
  146. 146. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages? • No as this is the same for 25 mm biopsy (Spectrum effect) • Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI... • Yes higher performance and safety than ALT, Forns, APRI • Is liver biopsy still useful?jeudi 26 janvier 2012
  147. 147. 26 janv. 2012 Summary: Responses to Questions • Is the perfect fibrosis biomarker possible? • No as 25 mm has 25% False P/N • There is a "gray zone" or "inaccurate zone" between intermediate stages? • No as this is the same for 25 mm biopsy (Spectrum effect) • Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI... • Yes higher performance and safety than ALT, Forns, APRI • Is liver biopsy still useful? • Yes but when everything else failedjeudi 26 janvier 2012
  148. 148. 26 janv. 2012 Summary: Responses to Questionsjeudi 26 janvier 2012
  149. 149. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease?jeudi 26 janvier 2012
  150. 150. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIHjeudi 26 janvier 2012
  151. 151. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy?jeudi 26 janvier 2012
  152. 152. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLDjeudi 26 janvier 2012
  153. 153. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan?jeudi 26 janvier 2012
  154. 154. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? • Yes: More sensitive in patients and more specific in general populationjeudi 26 janvier 2012
  155. 155. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? • Yes: More sensitive in patients and more specific in general population • Yes: Less sensitive to Activity and Steatosisjeudi 26 janvier 2012
  156. 156. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? • Yes: More sensitive in patients and more specific in general population • Yes: Less sensitive to Activity and Steatosis • Yes: FibroMax takes into account necrosis, inflammation and steatosisjeudi 26 janvier 2012
  157. 157. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? • Yes: More sensitive in patients and more specific in general population • Yes: Less sensitive to Activity and Steatosis • Yes: FibroMax takes into account necrosis, inflammation and steatosis • Rational of FibroTest components?jeudi 26 janvier 2012
  158. 158. 26 janv. 2012 Summary: Responses to Questions • Performance of Fibrotest according to liver disease? • Similar diagnostic value for HCV, HBV, ALD, NAFLD, AIH • What is the prognostic value of FibroTest vs biopsy? • At least similar for HCV, HBV, ALD, preliminary for NAFLD • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? • Yes: More sensitive in patients and more specific in general population • Yes: Less sensitive to Activity and Steatosis • Yes: FibroMax takes into account necrosis, inflammation and steatosis • Rational of FibroTest components? • Yes: Key proteins, validated proteomicsjeudi 26 janvier 2012
  159. 159. 26 janv. 2012 Anticipated Frequently Asked Questionsjeudi 26 janvier 2012
  160. 160. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest?jeudi 26 janvier 2012
  161. 161. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide linesjeudi 26 janvier 2012
  162. 162. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • Francejeudi 26 janvier 2012
  163. 163. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • France • Polandjeudi 26 janvier 2012
  164. 164. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • France • Poland • Romaniajeudi 26 janvier 2012
  165. 165. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • France • Poland • Romania • Israeljeudi 26 janvier 2012
  166. 166. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • France • Poland • Romania • Israel • Turkeyjeudi 26 janvier 2012
  167. 167. 26 janv. 2012 Anticipated Frequently Asked Questions • Are the authors credible due to their possible conflict of interest? • Yes: many independent validation studies and official guide lines • France • Poland • Romania • Israel • Turkey • EASLjeudi 26 janvier 2012
  168. 168. 26 janv. 2012 But: Savoir répondre à ce QCM: 84jeudi 26 janvier 2012
  169. 169. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 84jeudi 26 janvier 2012
  170. 170. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 84jeudi 26 janvier 2012
  171. 171. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 1.1. Faux c’est 1/4 84jeudi 26 janvier 2012
  172. 172. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 1.1. Faux c’est 1/4 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 84jeudi 26 janvier 2012
  173. 173. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 1.1. Faux c’est 1/4 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 2.1. Faux Relativement au FibroTest la biopsie est plus handicapée pour F1vsF2 84jeudi 26 janvier 2012
  174. 174. 26 janv. 2012 But: Savoir répondre à ce QCM: Parmi les 5 propositions suivantes concernant les performances relatives de la biopsie du foie (de 25 mm) par rapport à un marqueur noninvasif comme le FibroTest lesquelles sont exactes ? 1. La biopsie se trompe moins d’une fois sur 4 pour l’estimation d’un stade de fibrose METAVIR 1.1. Faux c’est 1/4 2. La biopsie du foie a une meilleure performance que le FibroTest pour le diagnostic de fibrose intermédiaire (Stade F2 vs F1) 2.1. Faux Relativement au FibroTest la biopsie est plus handicapée pour F1vsF2 3. Une biopsie de 25 mm peut avoir des faux négatifs pour le diagnostic de fibrose avancée (stades F2F3F4) mais très rarement des faux positifs. 84jeudi 26 janvier 2012

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