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25 janv. 2010




                             Biomarkers of Liver Injury
                        in a World without Gold ...
25 janv. 2010


     Population at risk of liver fibrosis, cirrhosis and
     hepatocellular carcinoma (Millions)

        ...
25 janv. 2010


     10 years of claims for diagnostic procedures 1993-2003:
     Severe Adverse Events and Deaths (French...
25 janv. 2010




                        n=100




                         n=400.000




lundi 25 janvier 2010          ...
25 janv. 2010




     FibroMAX: HCV-HBV-ALD-NAFLD


                                    NashTest


                   Act...
25 janv. 2010




     Anticipated Frequently Asked Questions
 • Is the perfect fibrosis biomarker possible?               ...
25 janv. 2010




     Rational of FibroTest:

     • Alpha 2 macroglobulin:               key protein for Collagenase met...
25 janv. 2010


                    In Situ                In Serum: FibroTest

                  Liver Injury            ...
25 janv. 2010




      In Situ events: Fibrosis and serum ApoA1 decrease




                                            ...
25 janv. 2010
                   Haptoglobin   Hemopexin




lundi 25 janvier 2010                                  10
25 janv. 2010




lundi 25 janvier 2010             11
25 janv. 2010

     Validated Fibrosis and Activity Biomarkers
     400.000 prescriptions in 35 countries
     Used by 80%...
25 janv. 2010




                             F0
                        Pas de Fibrose




lundi 25 janvier 2010        ...
25 janv. 2010




                             F1
                        Fibrose minime




lundi 25 janvier 2010        ...
25 janv. 2010




                              F2
                        Fibrose modérée




lundi 25 janvier 2010      ...
25 janv. 2010




                               F3
                        Fibrose importante




lundi 25 janvier 2010  ...
25 janv. 2010




                             F4
                        Fibrose sévère




lundi 25 janvier 2010        ...
25 janv. 2010




     Message I: Appropriate methods

           • Imperfect Gold Standard


           • Spectrum bias

...
25 janv. 2010




     Message II: Appropriate markers

           • Hepatologist: Must


           • GP and Screening: S...
25 janv. 2010




     Fibrosis estimates: Profile A

     • “Biopsy is still the gold standard”


     • “Biomarkers on th...
25 janv. 2010




         N Engl J Med 2001




lundi 25 janvier 2010                  21
25 janv. 2010




                        Risk of
                  chronic liver disease


                              ...
25 janv. 2010




     Fibrosis estimates: Profile B

     • “Too many false positive/false negative for intermediate stage...
lundi 25 janvier 2010   24
25 janv. 2010




lundi 25 janvier 2010             25
Biopsy has the same «Gray Zone»
                     Bedossa Hepatology 2003

                         25mm Biopsy



    ...
25 janv. 2010




     Fibrosis estimates: Profile C

     • “Still risk of severe adverse events for liver biopsy”


     ...
25 janv. 2010


                           Chronic Hepatitis B or C


                               FibroTest ActiTest

 ...
25 janv. 2010




lundi 25 janvier 2010             29
25 janv. 2010




    AUROC 5 mm = 0.75
    AUROC 15 mm = 0.82
    AUROC 25 mm = 0.89




  “We showed that with 25-mm lon...
25 janv. 2010

     Parkes et al review, J Hepatol 2006:
     An illustration of obsolete methodology using imperfect gold...
25 janv. 2010




                        Poynard et al APT 2007




lundi 25 janvier 2010                                ...
25 janv. 2010




     Imperfect Gold Standard: Summary

     • Entire liver is the perfect Gold Standard


     • Biopsy ...
25 janv. 2010




                FibroTest: from blood donors to cirrhotics (n=1,570)

                        1.00
     ...
25 janv. 2010




     FibroTest accuracy for the diagnosis of advanced fibrosis

     • 38 Published Studies


     • 7.98...
25 janv. 2010




     FibroTest in Chronic Hepatitis B: 3,303 patients

     • Myers, J Hepatol 2003 n=209

     • Poynar...
Kinetics of fibrosis according to baseline stages                             25 janv. 2010


                          In ...
25 janv. 2010




                 A New simple definition of low risk patients




                                 Ngo Pl...
25 janv. 2010




             A New simple definition of HBV Inactive Carrier




                              Viral Load...
25 janv. 2010



     Survival according to definition of inactive carrier based on FibroTest-
     ActiTest normal values ...
25 janv. 2010


     Summary:
     FibroTest-ActiTest in patients with chronic hepatitis B

     • Similar accuracy than i...
25 janv. 2010




     Analyses of Discordances

   Reference                        25 mm Biopsy                         ...
25 janv. 2010


    HCV: Stage transitions
    Interferon-Ribavirin: Advanced baseline fibrosis

                          ...
25 janv. 2010


     HCV n=416
     Mean FibroTest (range 0.00-1.00)
                        Baseline             12mo/EOT...
25 janv. 2010


   HCV n=416
   Mean Liver Stiffness Measurements (range 0-75 kPa )
                        Baseline      ...
25 janv. 2010


   HCV n=92
   Mean Fibrotest and Actitest
                Baseline               12 weeks   24 weeks     ...
25 janv. 2010



     HBV: Adefovir Trial
     Incoherence between Biopsy and Virological results

                       ...
25 janv. 2010




                        Oliveri WJG 2008


lundi 25 janvier 2010                      48
25 janv. 2010


 537 Prospective Cases Same day Biopsy and FibroTest
 Cause of errors in the 154 (29%) cases with discorda...
25 janv. 2010




                               Bedossa et al, Hepatology 2003




                        Poynard et al,...
25 janv. 2010




     FibroTest validation in “difficult to diagnose patients”

     • HIV-HCV: 	            Myers 2003, C...
25 janv. 2010

       FibroTest in the follow-up of liver transplanted patients: a pilot study




                       ...
FibroTest Global Quality Estimates




                       High Risk                 High Risk
                 False P...
Classical risk of errors




                        New risk of errors




lundi 25 janvier 2010                         ...
25 janv. 2010




     Prognostic value

     • FibroTest in HCV: Ngo, Clin Chem 2006


     • FibroTest in HBV: Ngo, Plos...
25 janv. 2010



  5 year Prognostic Value of FibroTest versus Biopsy Fibrosis Staging
  Survival Without HCV Complication...
HCV Survival according to FibroTest classes




                        N=537 NGO Clin Chem 2006


    HBV Survival accord...
25 janv. 2010




lundi 25 janvier 2010             58
25 janv. 2010

                        AST/ALT
                        Risk false
                         positive




lu...
25 janv. 2010




                    Quality of Patented Liver Biomarkers

                                      Nb      ...
FibroTest!
                            First Line!




                        Reference Center
                          ...
25 janv. 2010




     FibroMAX: HCV-HBV-ALD-NAFLD


                                    NashTest


                   Act...
25 janv. 2010


     SteatoTest for Steatosis
     744 patients 140 controls
     GGT AUROC=0.66          SteatoTest      ...
25 janv. 2010




     New concept in liver diseases

     • Biomarkers are for Hepatologists


           • the HDL-Chole...
25 janv. 2010




     Summary: Responses to Questions
 • Is the perfect fibrosis biomarker possible?

       • No as 25 mm...
100%          France: 12,000,000 at Risk

                                   F0

                                   F1
   ...
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Du 2010 Tp Biomarkers Output

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Du 2010 Tp Biomarkers Output

  1. 1. 25 janv. 2010 Biomarkers of Liver Injury in a World without Gold Standards Thierry Poynard + AP-HP Groupe Hospitalier Pitié Salpêtrière, UPMC Liver Center, Université Paris 6, INSERM U680, Biopredictive France LiverCenter lundi 25 janvier 2010 1
  2. 2. 25 janv. 2010 Population at risk of liver fibrosis, cirrhosis and hepatocellular carcinoma (Millions) No advanced fibrosis Advanced fibrosis Insulin resistance Alcool consumption Hepatitis B Hepatitis C Hemochromatosis 0 150 300 450 600 2 lundi 25 janvier 2010 2
  3. 3. 25 janv. 2010 10 years of claims for diagnostic procedures 1993-2003: Severe Adverse Events and Deaths (French Insurance) Technic Severe Adverse Events Deaths ERCP 71 30 Liver Biopsy* 11 5 Ultrasound-Endoscopy 4 2 *1 death /8,000 biopsies if one claim out of 2 deaths Standard severe adverse events prevalence: 3/1,000 Poynard T. Rev Med Interne 2007 lundi 25 janvier 2010 3
  4. 4. 25 janv. 2010 n=100 n=400.000 lundi 25 janvier 2010 4
  5. 5. 25 janv. 2010 FibroMAX: HCV-HBV-ALD-NAFLD NashTest ActiTest AshTest FibroMAX FibroTest SteatoTest 5 lundi 25 janvier 2010 5
  6. 6. 25 janv. 2010 Anticipated Frequently Asked Questions • Is the perfect fibrosis biomarker possible? No • There is a "gray zone" or "inaccurate zone" between intermediate stages? No • Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI... Yes • Is liver biopsy still useful? Yes • Same performance of Fibrotest in HCV, HBV, ALD, NAFLD? Yes • Similar prognostic value of FibroTest vs biopsy? Yes • Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? Yes • Rational of FibroTest components? Yes • Are the authors credible due to their possible conflict of interest? Yes lundi 25 janvier 2010 6
  7. 7. 25 janv. 2010 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 • Haptoglobin Imbert Bismut 2001, Langlois 2006, Watanabe 2009 lundi 25 janvier 2010 7
  8. 8. 25 janv. 2010 In Situ In Serum: FibroTest Liver Injury Alpha2Macroglobulin Total Bilirubin Gamma GT Apolipoprotein A1 Fibrotic Matrix Activated Stellate Cells Haptoglobin Imbert-Bismut, Lancet 2001 lundi 25 janvier 2010 8
  9. 9. 25 janv. 2010 In Situ events: Fibrosis and serum ApoA1 decrease Trapping Apo A1 Down Regulation Paradis Cell Mol Biol 1996, Paradis Hepatology 1996, Mathurin Hepatology 1996. lundi 25 janvier 2010 9
  10. 10. 25 janv. 2010 Haptoglobin Hemopexin lundi 25 janvier 2010 10
  11. 11. 25 janv. 2010 lundi 25 janvier 2010 11
  12. 12. 25 janv. 2010 Validated Fibrosis and Activity Biomarkers 400.000 prescriptions in 35 countries Used by 80% of French Hepatologists, first line FibroTest ActiTest Castera J Hepatol 2007 12 lundi 25 janvier 2010 12
  13. 13. 25 janv. 2010 F0 Pas de Fibrose lundi 25 janvier 2010 13
  14. 14. 25 janv. 2010 F1 Fibrose minime lundi 25 janvier 2010 14
  15. 15. 25 janv. 2010 F2 Fibrose modérée lundi 25 janvier 2010 15
  16. 16. 25 janv. 2010 F3 Fibrose importante lundi 25 janvier 2010 16
  17. 17. 25 janv. 2010 F4 Fibrose sévère lundi 25 janvier 2010 17
  18. 18. 25 janv. 2010 Message I: Appropriate methods • Imperfect Gold Standard • Spectrum bias • Analysis of discordances Bedossa Hepatology 2003, Poynard Clin Chem 2005, Poynard Clin Chem 2007, Poynard GCB 2008 lundi 25 janvier 2010 18
  19. 19. 25 janv. 2010 Message II: Appropriate markers • Hepatologist: Must • GP and Screening: Simple • Industry: Rapid • Health Authorities: Surrogate Endpoint lundi 25 janvier 2010 19
  20. 20. 25 janv. 2010 Fibrosis estimates: Profile A • “Biopsy is still the gold standard” • “Biomarkers on the market are not accurate enough” • “I steel need biopsy for all my patients” • “Biomarkers only if contra-indications of liver biopsy” 10 % Biopsy Biomarker 90 % lundi 25 janvier 2010 20
  21. 21. 25 janv. 2010 N Engl J Med 2001 lundi 25 janvier 2010 21
  22. 22. 25 janv. 2010 Risk of chronic liver disease If contra-indication Biomarker Biopsy lundi 25 janvier 2010 22
  23. 23. 25 janv. 2010 Fibrosis estimates: Profile B • “Too many false positive/false negative for intermediate stages”, “Gray zone” • “Ok for the next generation of biomarkers when they will demonstrate 90% AUROCs for bridging fibrosis (F2)” • “Ok for cirrhosis biomarkers or elastography, as AUROCs = 90%” Biopsy Biomarker 50 % 50 % lundi 25 janvier 2010 23
  24. 24. lundi 25 janvier 2010 24
  25. 25. 25 janv. 2010 lundi 25 janvier 2010 25
  26. 26. Biopsy has the same «Gray Zone» Bedossa Hepatology 2003 25mm Biopsy F4-F3 F2-F1 F1-F0 25% 25% 25% False Positive False Positive and Negative False Negative lundi 25 janvier 2010 26
  27. 27. 25 janv. 2010 Fibrosis estimates: Profile C • “Still risk of severe adverse events for liver biopsy” • “Biopsy has same limitations for adjacent stages 10 % than validated biomarkers: there is no intermediate gray zone” • “No rational or evidence based for biopsy as first line test” 90 % • “Biopsy still necessary if biomarkers results at high risk of false positive/negative” Biopsy Biomarker lundi 25 janvier 2010 27
  28. 28. 25 janv. 2010 Chronic Hepatitis B or C FibroTest ActiTest Fibroscan if FibroTest not applicable Advanced Fibrosis No Advanced Fibrosis Severe Activity No Severe Activity FibroTest Hepatologist every 2-4 years lundi 25 janvier 2010 28
  29. 29. 25 janv. 2010 lundi 25 janvier 2010 29
  30. 30. 25 janv. 2010 AUROC 5 mm = 0.75 AUROC 15 mm = 0.82 AUROC 25 mm = 0.89 “We showed that with 25-mm long biopsy specimens, only 75% were scored correctly and 65% for 15- mm biopsy specimens” Bedossa Hepatology 2003 lundi 25 janvier 2010 30
  31. 31. 25 janv. 2010 Parkes et al review, J Hepatol 2006: An illustration of obsolete methodology using imperfect gold standard as a perfect gold standard • If the Parkes et al statements and conclusions were applied to 25 mm liver biopsy, which only scored correctly in 75% using perfect gold standard: • “The 25 mm liver biopsy have a place in assessment of fibrosis to rule-in or rule-out fibrosis, but in individual patients cannot differentiate the stages of fibrosis reliably. “ lundi 25 janvier 2010 31
  32. 32. 25 janv. 2010 Poynard et al APT 2007 lundi 25 janvier 2010 32
  33. 33. 25 janv. 2010 Imperfect Gold Standard: Summary • Entire liver is the perfect Gold Standard • Biopsy is an imperfect Gold Standard • Biopsy 25 mm has 25% false positive/ negative versus entire liver • Waiting for 90% AUROCs for bridging fibrosis biomarker is a dream in a world without Gold Standards Bedossa Hepatology 2003, Poynard Clin Chem 2005, Poynard Clin Chem 2007, Poynard GCB 2008 lundi 25 janvier 2010 33
  34. 34. 25 janv. 2010 FibroTest: from blood donors to cirrhotics (n=1,570) 1.00 Fibrotest 0.67 0.33 0.00 Blood Donors F0 F1 F2 F3 F4 Poynard Clin Chem 2004, Comp Hepatol 2004 lundi 25 janvier 2010 34
  35. 35. 25 janv. 2010 FibroTest accuracy for the diagnosis of advanced fibrosis • 38 Published Studies • 7.985 Patients • Standardized AUROC • 0.84 (0.83-0.86) The best you can obtain with 20mm biopsy is 0.90 Bedossa 2003 • Advanced Fibrosis Friedrich Rust et al Gastroenterology 2008, Halfon et al GCB 2008 lundi 25 janvier 2010 35
  36. 36. 25 janv. 2010 FibroTest in Chronic Hepatitis B: 3,303 patients • Myers, J Hepatol 2003 n=209 • Poynard, Am J Gastro 2005 n=283 • Cales, Hepatology 2005 n=46 • Sebastiani, World J Gastro 2006 n=110 • Coco, JVH 2007 n=93 • Zhao Chines J Pract Int Med 2007 n=123 • Poynard, JVH 2008 n=924 • Ngo, 2008 PlosONE 2008 n=1,300 • Abstracts: Castera, J Hepatol 2006 n=154; Hilleret, J Hepatol 2006 n=184, lundi 25 janvier 2010 36
  37. 37. Kinetics of fibrosis according to baseline stages 25 janv. 2010 In HBV patients treated with lamivudine 2 years n=283 FibroTest-FibroSURE 1.00 0.73 0.75 0.52 F2F3F4 P=0.01 0.50 0.25 F0F1 NS 0.00 Baseline 6 mo 12 mo 24 mo 44 Cirrhosis: 42 (95%) improvement at 24 months; Significant regression (>0.30) in 14/44 (32%) Dienstag et al Gastroenterol 2003. Poynard et al Am J G 2005 lundi 25 janvier 2010 37
  38. 38. 25 janv. 2010 A New simple definition of low risk patients Ngo PlosONE 2008 lundi 25 janvier 2010 38
  39. 39. 25 janv. 2010 A New simple definition of HBV Inactive Carrier Viral Load < Log5 + FibroTest<= 0.27 ActiTest <= 0.29 Ngo PlosONE 2008 lundi 25 janvier 2010 39
  40. 40. 25 janv. 2010 Survival according to definition of inactive carrier based on FibroTest- ActiTest normal values in untreated patients FibroTest and Survival without Survival without Survival Paired Overall Survival ActiTest complications death Controls** Normal 99.6 % 100% 100% 100% n=289 (99.5-99.6) Not normal 91.2 % 94.7 % 91.2 % 98.4 % n=208* (84.2-98.1) (89.7-99.8) (84.2-98.1) (97.6-99.1) Both normal values: FibroTest <=0.27 and ActiTest <=0.29 * Survivals of patients with abnormal FibroTest and ActiTest were lower than those of normal FibroTest and ActiTest (p<0.005) ** Overall survivals of patients with abnormal FibroTest and ActiTest were lower to those in paired controls (p<0.005) Ngo PlosONE 2008 lundi 25 janvier 2010 40
  41. 41. 25 janv. 2010 Summary: FibroTest-ActiTest in patients with chronic hepatitis B • Similar accuracy than in HCV, validated at baseline, during and after HBV treatment • Discordances are also due to biopsy failure in at least 50% of cases • More sensitive than biopsy • Same prognostic value than biopsy • Permitted a better definition of non active carrier 41 lundi 25 janvier 2010 41
  42. 42. 25 janv. 2010 Analyses of Discordances Reference 25 mm Biopsy Surgical Biopsy • Failures of biopsy • Failures of FibroTest • Failures of elastography Discordance 30% between 2 estimates Reguev AJG 2003, Poynard Clin Chem 2004, Poynard APT 2007, Coco JVH 2007, Poynard PlosOne 2008 42 lundi 25 janvier 2010 42
  43. 43. 25 janv. 2010 HCV: Stage transitions Interferon-Ribavirin: Advanced baseline fibrosis Low quality biopsy Discordant Cases 0/15 >= 25mm both 7/15 >= 15mm both Low quality biopsy 2/24 >= 25mm both SVR n=107 NR n=105 10/24 >= 15mm both 100 % 75 % Progression Stable 50 % Regression 25 % 0 % Fibrotest Biopsy Fibrotest Biopsy Poynard et al, Hepatology 2003 43 lundi 25 janvier 2010 43
  44. 44. 25 janv. 2010 HCV n=416 Mean FibroTest (range 0.00-1.00) Baseline 12mo/EOT 24mo/EOF Slow increase = Slow decrease = Sensitivity Not related to activity 0,60 0,48 0,36 0,24 0,12 Control (n=304) 0 SVR (n=70) Vergniol et al JVH 2009 lundi 25 janvier 2010 44
  45. 45. 25 janv. 2010 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 2009 lundi 25 janvier 2010 45
  46. 46. 25 janv. 2010 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 2006 lundi 25 janvier 2010 46
  47. 47. 25 janv. 2010 HBV: Adefovir Trial Incoherence between Biopsy and Virological results False Positive False Negative Low quality biopsies Low quality biopsies Median 11mm Median 9mm Treated PCR Neg Placebo 100 % 75 % Progression Stable 50 % Regression 25 % 0 % Biopsy Biopsy 47 lundi 25 janvier 2010 47
  48. 48. 25 janv. 2010 Oliveri WJG 2008 lundi 25 janvier 2010 48
  49. 49. 25 janv. 2010 537 Prospective Cases Same day Biopsy and FibroTest Cause of errors in the 154 (29%) cases with discordant results 2% FT-AT vs 18% Biopsy (p<0.001) Poynard et al, Clin Chem 2004 49 lundi 25 janvier 2010 49
  50. 50. 25 janv. 2010 Bedossa et al, Hepatology 2003 Poynard et al, Clin Chem 2004 Quality of Liver Biopsy: Pitie experience 1,773 biopsies: 16% > 25mm Median 15 mm lundi 25 janvier 2010 50
  51. 51. 25 janv. 2010 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 51 lundi 25 janvier 2010 51
  52. 52. 25 janv. 2010 FibroTest in the follow-up of liver transplanted patients: a pilot study Relapse/Reject n=8 P<0.001 No Relapse/Reject n=15 Before LT 24-72 h 7 days 2 weeks 4 weeks 24 weeks 48 weeks Hamelet EASL 2008 lundi 25 janvier 2010 52
  53. 53. FibroTest Global Quality Estimates High Risk High Risk False Positive Negative False Positive Negative 0/954 (0%) 0/7494 (0%) FibroScan (Roulot et al 2008) 7.1 kPa 12.6% false positives ? High Risk High Risk False Positive Negative False Positive Negative 0.97% 1.97% lundi 25 janvier 2010 53
  54. 54. Classical risk of errors New risk of errors lundi 25 janvier 2010 54
  55. 55. 25 janv. 2010 Prognostic value • FibroTest in HCV: Ngo, Clin Chem 2006 • FibroTest in HBV: Ngo, PlosOne 2008 • FibroTest in ALD: Naveau, Hepatology 2008 • FibroTest in Mixed severe cirrhosis: Thabut, AASLD 2007 55 lundi 25 janvier 2010 55
  56. 56. 25 janv. 2010 5 year Prognostic Value of FibroTest versus Biopsy Fibrosis Staging Survival Without HCV Complications AUROCs FibroTest 0.96 vs Biopsy 0.91 P=0.01 Pugh 0.80 P=0.006 APRI 0.82 P=0.03 Forns 0.86 P=0.04 N=537 NGO Clin Chem 2006 56 lundi 25 janvier 2010 56
  57. 57. HCV Survival according to FibroTest classes N=537 NGO Clin Chem 2006 HBV Survival according to FibroTest classes lundi 25 janvier 2010 57
  58. 58. 25 janv. 2010 lundi 25 janvier 2010 58
  59. 59. 25 janv. 2010 AST/ALT Risk false positive lundi 25 janvier 2010 59
  60. 60. 25 janv. 2010 Quality of Patented Liver Biomarkers Nb Nb Quality Test Studies Patients Score FibroTest 33 6,549 60/62 FibroSpect 4 463 30/62 FibroMeter 2 1,041 26/62 ELF 3 1,134 30/62 HepaScore 3 757 25/62 Poynard et al, Advances in Clinical Chemistry, 2008, GCB 2008 lundi 25 janvier 2010 60
  61. 61. FibroTest! First Line! Reference Center FibroScan for! Confirmation ! Biopsy! If discordances! lundi 25 janvier 2010 61
  62. 62. 25 janv. 2010 FibroMAX: HCV-HBV-ALD-NAFLD NashTest ActiTest AshTest FibroMAX FibroTest SteatoTest 62 lundi 25 janvier 2010 62
  63. 63. 25 janv. 2010 SteatoTest for Steatosis 744 patients 140 controls GGT AUROC=0.66 SteatoTest AUROC=0.80 ALT AUROC=0.61 Poynard Comp Hepatol 2005 lundi 25 janvier 2010 63
  64. 64. 25 janv. 2010 New concept in liver diseases • Biomarkers are for Hepatologists • the HDL-Cholesterol for Cardiologists • Using biomarkers validated for the frequent chronic liver diseases, • GP will screen advanced fibrosis for Hepatologists, • Who have good treatment, at least for HCV and HBV 64 lundi 25 janvier 2010 64
  65. 65. 25 janv. 2010 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 failed lundi 25 janvier 2010 65
  66. 66. 100% France: 12,000,000 at Risk F0 F1 10% F2 Test F3 5% F4 0.1% Death 15,000/year lundi 25 janvier 2010 66

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