Du 2015 poynard biomarkers

1. 7 févr. 2012
LiverCenter
Non Invasive Biomarkers
in chronic hepatitis C and B
!
DU 2015
Thierry Poynard
+
AP-HP Groupe Hospitalier Pitié Salpêtrière,
UPMC Liver Center, Université Paris 6,
INSERM U680, Biopredictive France

2. Serum Biomarker Imaging Biomarker
FibroTest
FibroMax
Choice
Hepatologist
Epidemiologist
GP
FibroScan
Aixplorer

3. 2
Biomarkers of liver injury in chronic hepatitis
• Unmet need
• Historic
• Methods and based evidence
• Guidelines in practice
2

4. FRANCE FIBROSIS ICEBERG
Biopsy: 2% (8 000 /yr)
FibroTest: 10% (50 000/yr)
Imaging: 10% (50 000/yr)
No-estimate: 78%
!
0.25 Million Chronic Hepatitis C
0.25 Million Chronic Hepatitis B

5. USA FIBROSIS ICEBERG
Biopsy: 1% (50 000 /yr)
FibroSure: 1% (50 000 /yr)
Imaging: 1% (50 000 /yr)
No-estimate: 97%
!
3 Millions Chronic Hepatitis C
1 Million Chronic Hepatitis B

6. "META-analysis of histological data in VIRal hepatitis"
Hepatology 1996
METAVIR
THE METAVIR cooperative group. Inter- and intra-observer variation, Hepatology 1995

7. 7 févr. 20127 févr. 2012
Viral necrosis
Activity
Fibrosis Steatosis
Alcohol
Ash
Nash
Liver
Injury

8. 8
7 févr. 2012
FibroMAX: HCV-HBV-ALD-NAFLD
ActiTest
FibroTest SteatoTest
AshTest
NashTest
FibroMAX
7

9. 2
Biomarkers of liver injury in chronic hepatitis
• Unmet need
• Historic
• Methods and based evidence
• Guidelines in practice
2

10. 7 févr. 2012
Fibrosis biomarkers: 24 years history
SJG 2008
n=100
n=1 million

11. 7 févr. 2012
Haptoglobin
Alpha2Macroglobulin
Apolipoprotein A1
Total Bilirubin
Gamma GT
In Situ In Serum: FibroTest
Imbert-Bismut, Lancet 2001
Liver Injury
Activated Stellate Cells
Fibrotic Matrix

12. 7 févr. 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 A1, A2M
• Haptoglobin
Paradis Cell Mol Biol 1996, Paradis Hepatology 1996, Mathurin Hepatology 1996, Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010

13. 2
Biomarkers of liver injury in chronic hepatitis
• Unmet need
• Historic
• Methods and based evidence
• Guidelines in practice
2

14. 7 févr. 2012
Period 1: 1991-2004 Optimistic
!
Looking for a fibrosis biomarker with accuracy > 90%

15. 7 févr. 2012
Biopsy
=
Gold Standard
Biopsy
=
0% False Positive
0% False Negative

16. 7 févr. 2012
Liver
Injury
Serum biomarker Imaging biomarker

17. F4
F1
F0
Fibrotic Liver
Disease
F2
F3
Hemorrhage Liver failure Cancer
FibroTest OK
AUROC >80%
FibroTest OK
FibroScan OK
AUROC >80%
«Gray Zone»: Biopsy
Imbert Bismut 2001, Castera 2005

18. 7 févr. 2012
Period 2: 2005-2009: Sceptic
!
Standard statistical methods were inappropriate
!
Period 3: 2010-2015
!
New methods

19. 19
7 févr. 2012
• 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
• Direct meta-analyses Poynard 2015
22
8 Key methodological issues:
Biopsy is no more a perfect gold standard

20. Sampling error:
AUROCs (F1 vs F2) of Biopsy vs Whole Liver according to length
Bedossa Hepatology 2003
AUROC 15 mm = 0.82
AUROC 25 mm = 0.89
«We showed that with 25-mm
long biopsy specimens, only 75%
were scored correctly»

21. 7 févr. 2012
F0 F1 F2 F3 F4
Inter-Observers variability:
Biopsy has lower inter-observers concordance for intermediate stages
Rousselet, Hepatology 2005

22. 22
7 févr. 2012
Discordances studies: independent endpoints
• 537 prospective cases hepatitis C
• 154 (29%) discordances FibroTest/Biopsy
• Error attributable
• To FibroTest: 2%
• To Biopsy: 18%
25
Poynard Clin Chem 2004, Halfon AJG 2006

23. F4.1
F1
F0
F2
F3
7 Stages
Presumed by Biomarkers
Decompensated
F4.2
F4.3
Varices
FibroTest
0.48
0.74
0.85
0.95
TE
7.1
9.5
20
50
12.5
0.58
CHC Poynard J Hepatol 2014
CHB Poynard J Hepatol 2014

24. 24
7 févr. 2012
• 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
29
3/7 key methodological issues not well understood
Biopsy is no more a perfect gold standard

25. F4
F1
F0
Fibrotic Liver
Disease
F2
F3
DANA=4
DANA=Difference between Advanced and non-advanced fibrosis stages
Obuchowski measure=AUROCs Pair-wise comparison between all stages
Black and White Spectrum
FibroTest AUROC=0.98

26. F4
F1
F0
Fibrotic Liver
Disease
F2
F3
DANA=1
DANA=Difference between Advanced and non-advanced fibrosis stages
Obuchowski measure=AUROCs Pair-wise comparison between all stages
Gray Spectrum
FibroTest AUROC=0.67

27. F4
F1
F0
Fibrotic Liver
Disease
F2
F3
DANA=2.5
DANA=Difference between Advanced and non-advanced fibrosis stages
Obuchowski measure=AUROCs Pair-wise comparison between all stages
FibroTest AUROC=0.85
Standard Spectrum

28. 7 févr. 2012
Hazardous Tables due to Spectrum Effect (1)
Interpretation of AUROC
AUROC Score* Biopsy length FibroTest and Spectrum
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 2007

29. 7 févr. 2012
Hazardous Tables due to Spectrum Effect (October 2012)
Ochi Hepatology 2012
Real-time tissue elastography cut-off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using
these cut-off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%-96.0% in all stages.
!
The area under the receiver operating characteristic curve of elastic ratio better correlated than
serum fibrosis markers in both early and advanced fibrosis stages.
!
Conclusion: Real-time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD. (HEPATOLOGY 2012;1271-1278)

30. 30
7 févr. 2012
• 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
29
3/7 key methodological issues not well understood
Biopsy is no more a perfect gold standard

31. Using 25 mm liver biopsy a perfect market cannot be validated
Black shading represents the set of conditions under which the AUROC values exceed what has already been observed
Metha J Hepatol 2009

32. 32
7 févr. 2012
Exceeding limits of biopsy:
>90% accuracy is impossible for advanced fibrosis
35
«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

33. 7 févr. 2012
Misleading presentation using biopsy as Gold-Standard
Boursier Hepatology 2012
Mathematically impossible with biopsy as «Gold Standard

34. 34
7 févr. 2012
• 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
29
3/7 key methodological issues not well understood
Biopsy is no more a perfect gold standard

35. 35
7 févr. 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 »
37

36. FibroTest/FibroSure has a Gray Zone

37. Biopsy has a Gray Zone

39. 39
7 févr. 2012
Review of fibrosis tests by Nguyen, Hepatology 2011
41

40. 7 févr. 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
Poynard, BMC 2005, J Hepatol 2011

41. 7 févr. 2012
The gray zone of liver biopsy: 27,864 virtual biopsies
Area
Fibrosis
(Log)
25 mm Liver Biopsies
Poynard Clin Gastro Hepatol 2012

42. 7 févr. 2012
The gray zone of liver biopsy: 27,864 virtual biopsies
Poynard Clin Gastro Hepatol 2012
Area
Fibrosis
(Log)
25 mm Liver Biopsies

43. Lower gray zone of FibroTest relative to biopsy
Lower gray zone F2vsF1 for FibroTest vs Biopsy
!
58% lower F2vsF1 vs F1vsF0
41% lower F2vsF1 vs F4vsF3.
Biopsy
n=27,864
Fibrotest
n=6500
Poynard Clin Gastro Hepatol 2012

44. 7 févr. 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 2011

45. 7 févr. 2012
Period 2: 2005-2009: Sceptic
!
Standard statistical methods were inappropriate
!
Period 3: 2010-2015
!
New methods

46. (c) BioPredictive 2008 - All Rights Reserved - No reproduction without written permission
Benefit/Risk must be evaluated for each change in the formula:

47. High Risk
False Positive Negative
5/954 (0.52%)
High Risk
False Positive Negative
38/7494 (0.51%)
FibroTest Global Quality Estimates
High Risk
False Positive Negative
3349/345,695 (0.97%)
High Risk
False Positive Negative
491/24,872 (1.97%)
FibroScan (Roulot et al 2008)
>7.1 kPa= 12.6%: False Positives ?
Poynard BMC Gastro 2011, Roulot J Hepatol 2008

48. (c) BioPredictive 2008 - All Rights Reserved - No reproduction without written permission
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%

49. 7 févr. 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 acid

50. 7 févr. 2012

51. 7 févr. 2012
Biopsy vs Serum marker
Main advantages/disadvantages
Serum Marker FibroTest
Less accurate for
intermediate stages
No grey zone relatively to
biopsy
Fibrosis only ActiTest/SteatoTest
Delays result proprietary
tests
1-48h
False positive/hemolysis/
inflammation/Gilbert
Yes but 0.97%
(3349/345695; 0.94-1.00)
Nguyen Hepatology, 2011 Poynard BMC Gastro 2011

52. 7 févr. 2012
Period 3: 2010-2015
!
Welcome in a world without perfect Gold Standard

53. 7 févr. 2012
!
Gold Standard
25 mm Biopsy 0%
False Positive
False Negative

54. 7 févr. 2012
Truth in the
Absence of
Gold Standard
25 mm Biopsy 25%
False Positive
False Negative

55. 7 févr. 2012
Area of fibrosis estimated by biopsy according to its length (mm) in subjects
scoring METAVIR F0 (no fibrosis) on large surgical section.
Area 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.
Cirrhosis
Advanced fibrosis
Poynard J Hepatol 2012

56. 7 févr. 2012
Poynard J Hepatol 2011
Truth
FibroTest FibroScan
5-30 mm Biopsy
ALT

57. 7 févr. 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
...
1 1 1 1 276 277.0
Poynard, J Hepatol 2011

58. 7 févr. 2012
FibroTest Se LSM Se Biopsie Se
Performance for Advanced Fibrosis: Sensitivity
The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness
Poynard, J Hepatol 2011

59. 7 févr. 2012
FibroTest Sp LSM Sp Biopsy Sp
Performance for Advanced Fibrosis: Specificity
The standard cutoffs: 0.48 FibroTest, 8.8 kPa Stiffness
Poynard, J Hepatol 2011

60. 7 févr. 2012
FibroTest Se LSM Se Biopsie Se
Performance for Cirrhosis: Sensitivity
The standard cutoffs: 0.74 FibroTest, 14.5 kPa Stiffness
Poynard, J Hepatol 2011

61. 7 févr. 2012
FibroTest Sp LSM Sp Biopsy Sp
Performance for Cirrhosis: Specificity
The standard cutoffs: for cirrhosis 0.74 for FibroTest, and 14.5 kilo-Pascal for stiffness (LSM)
Poynard, J Hepatol 2011

63. 7 févr. 2012
SWE Fibrotest 1 TE-M Fibrotest 2 TE-XL FibroTest 3
Poynard, J Hepatol 2013
Performances for diagnosis of Cirrhosis (HCV, HBV, NAFLD, ALD)
of FibroTest, and Elastography: Transient M-XL probes and Share Wave
Latent Class Model: Best model for FibroTest with TE-XL or SWE (Likelihood ratio test 5.5, 6.9)
n = 322 simultaneous reliable tests

64. 7 févr. 2012
Period 3: 2010-2015
!
Improving serum biomarker

66. 66
7 févr. 2012
HCV-GenoFibroTest: Liver injury, Virus Resistance, Host
Genes for treatment Response and Tolerance
88
ActiTest
FibroTest SteatoTest
IL28B
HCV-
GenoFibroTest
Viral Load
Viral Resistance
ITPA
UGT1A1
Genotype

67. 7 févr. 2012
Period 3: 2010-2015
!
Combining serum and imaging biomarkers

69. 69
7 févr. 2012
• 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
79
Elastography

70. 7 févr. 2012
Oliveri WJG 2008

71. 7 févr. 2012
Pitfalls of Fibroscan
3.1% Failures and Unreliable results 15.8%

72. 7 févr. 2012
Choice of FibroScan Cutoffs
!
Castera 2005, Ketanneh 2007
Roulot 2008
!
For F2: 7.1 or 8.8 kPa ?
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 ?
!
No rationale for changing cutoff
according to liver disease
F2 8.8 kPa F4 14.5 kPa
F4 0.73
F2 0.48
Poynard PlosOne 2008

73. A la Parisienne
Fibrotest
First Line
If not interpretable
Biopsy
FibroTest ActiTest
If not interpretable
Fibroscan
98%
<1%
2%
Prevalence

74. Serum biomarker
FibroTest
Imaging biomarker
FibroScan
Elasto-FibroTest
Poynard, CRHG 2012

75. 75
7 févr. 2012
Elasto-FibroTest®
• 1289 patients with CHC and 604 healthy volunteers
• Appropriate methods
• Obuchowski measures
• Methods without Gold Standard
66
Poynard, CRHG 2012

76. 76
7 févr. 2012
Elasto-FibroTest®
1289 patients with CHC and 604 healthy volunteers
• 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.
67
Poynard, CRHG 2012

77. 7 févr. 2012
Poynard, CRHG 2012

78. 8-week $ 63,000 12-Week $ 94,500 24-week $ 189,000
$ 1125 per pill

79. FibroTest used to identify cirrhosis at baseline or for follow-up

81. 2
FibroTest strengths
1.Same algorithms and cutoffs for all chronic liver diseases: chronic hepatitis C (CHC) and B (CHB),
Alcoholic Liver Disease ALD, and Non-Alcoholic Fatty Liver Disease (NAFLD)
2.Most validated fibrosis biomarker (CHC, CHB, ALD, NAFLD), including repeated biopsies, prognostic
studies, meta-analyses, guidelines, and cost-effectiveness
3.Combined with biomarker of Activity (ActiTest), Steatosis (SteatoTest), Alcoholic Hepatitis (AshTest) and
Non-Alcoholic Steato-Hepatitis (NashTest), IL28B (GenoFibroTest) and elastography (ElastoFibroTest).
4.Security algorithms to prevent false positive/negative (Gilbert, Hemolysis,) and possible analytical errors
5.>95% applicability with more than 1 million prescriptions,
6.Used for inclusion of patients in phase 3 trials of DAA
2

82. Number of
Studies
Quality Consistency Precision
Strength of
evidence
32 Fair High High High
Chou, Ann Int Med 2013
FibroTest is the most validated test in Chronic Hepatitis C:
!
Strength-of-evidence domains and overall ratings

83. Fibrosis Cirrhosis
Number studies 25 11
Number patients 9549 6893
AUROC 0.79 (0.70-0.89) 0.86 (0.71-0.92)
Applicability >95% >95%
Afdhal, JVH Nov 2013
Chou, Ann Int Med 2013
FibroTest performances for
clinically significant fibrosis and cirrhosis in CHC

84. Competitors
• Transient elastography first generation: Fibroscan
!
• Aspartate amino transferase - Platelet Ratio Index (APRI)
84

85. 23 sept. 2014
Performances for cirrhosis diagnosis
FibroTest Fibrosure
Transient
elastography
AUROC* 0.86 (0.71-0.92) 0.94 (0.93-0.95)
Applicability >95% 80 %
Afdhal, JVH Nov 2013
Chou, Ann Int Med 2013
Not in intention to
diagnose

86. Fibrosis F2F3F4 F4 All stages
Method AUROC (95%) AUROC Obuchowski
FibroTest 0.83 (0.81-0.85) 0.88 (0.87-0.91) 0.89 (0.88-0.89)
FibroScan 0.69 (0.67-0.71) 0.77 (0.76-0.79) 0.74 (0.74-0.75)
P value <0.01 <0.01 <0.01
FibroScan: 7.1 kPa cutoff for F2: 12.6% false positives ?!
Poynard CRHG 2011, Roulot J Hepatol 2008
Higher performance of FibroTest vs FibroScan FF3F4 and F4
in «intention to diagnose» 1893 patients with chronic hepatitis C and 604
healthy volunteers

89. Competitors
• Transient elastography first generation: Fibroscan
!
• Aspartate amino transferase - Platelet Ratio Index (APRI)
89

90. APRI has lower performance than Fibrotest
!
due to its high variability
1. Analytical variability: ULN-AST definitions
2. Interaction with non-fibrosis features
• Activity and AST
• Steatosis and AST

91. Clin Res Hepatol Gastro 2014

92. High variability of APRI: methods
• Overview literature of AST-ULN: 26-49 IU/L
• 7521 healthy volunteers
• 393 blood donors
• 1651 patients with CHC, biopsy, FibroTest, APRI

93. High variability of APRI associated with ULN definitions:
!
Impact on diagnosis performance
• Range of AST-ULN in controls: 26-49 IU/L
• According gender, BMI and cholesterol
!
• Fibrosis prevalence in CHC: spectrum effect
• Clinically significant fibrosis (F2F3F4): 35-69%
• Cirrhosis (F4): 11-32%

94. Impact on performance: Obuchowski measure
!
Change in AUROCs between fibrosis stages
ULN 26 IU/L ULN >=30 IU/L
APRI 0,862 0,820
FibroTest 0,867 0,867
Significance 0,30 <0,0001

95. Higher Diagnostic and Prognostic performance of FibroTest
versus APRI in CHC
Poynard, Ann Int Med 2013

96. 5 years prognostic value in chronic hepatitis B
FibroTest better biomarker
de Ledinghen APT 2013
LSM Not in intention to
diagnose

97. Biomarke
r
Analytic
variability
Risk false
positive due to
Activity
Fasting Applicability Investment Cost
FibroTest < 7% no (ActiTest) no >95% 0 38€-200$
FibroScan Inter Observer yes yes 80 %
60,000€
200,000$
38€-350$
APRI
Hazard of AST
Upper Limit
Normal
yes no ? 0 7€-40 $
Castera Hepatology 2010, Afdhal JVH 2013, Chou Ann Int Med 2013,
Poynard BMC Gastro 2011, Poynard Ann Int Med 2013
Pro and Con of the three «Standard of Care» biomarkers

98. 2
Biomarkers of liver injury in chronic hepatitis
• Unmet need
• Historic
• Methods and based evidence
• Guidelines in practice
2

101. EASL Recommendations onTreatment of Hepatitis C, April 2014

102. 13
Three reasons to assess fibrosis stages in 2014
!
•Expensive IFN-free regimen, priority to severe fibrosis
•Cirrhosis could need longer treatment
•Viral cure is not fibrosis cure
Cohen, Science 2013, Afdahl NEJM 2014, Poynard J Hepatol 2013

103. FibroTest similar to biopsy for estimating fibrosis progression
Progression to cirrhosis in 2472 patients
Biopsy FibroTest
Poynard et al, J Hepatol 2012

104. Response is associated with longer treatment in cirrhosis stage*
vs non-cirrhosis in experienced Genotype 1, treated by Sofosbuvir-
Ledispasvir:
80
85
90
95
100
12 weeks 24 weeks
Cirrhosis No Cirrhosis
Afdahl NEJM 2014*cirrhosis stage defined by biopsy or FibroTest
n=22 n=22n=87 n=87

105. 23 sept. 2014
Survival without liver complications
n = 933!
NS
SVR n=4
3 HCC
1 Cholangiocarcinoma
All F4 before SVR
2 F2 after
Poynard, J Hepatol 2013

106. Cirrhosis regression in SVR n=24/43 ( 56%)
FibroTest = 0.74
Poynard, J Hepatol 2013

107. Cirrhosis Occurrence in SVR n=15/128 (12%)
FibroTest = 0.74
Poynard, J Hepatol 2013

108. Fibrosis Progression in 13 HBV Sustained Virological Responders
with occurrence of HepatoCellular Carcinoma at 10 years
FibroTest = 0.74 = F4
Poynard, J Hepatol 2014
F1: Subsaharan female, BMI 37 kg/m2

109. Standard of Care in 2014
FibroTest, not perfect....but...
The most validated biomarker of liver fibrosis and activity
!
!
Better performance than APRI
!
Better than FibroScan in intention to diagnose and for
screening in general population

110. F4
F1
F0
France: 12,000,000 at Risk100%
5%
Death 15,000/year0.1%
Biomarker10% F2
F3