biomarkers of liver injury.pdf

13 janv. 2011

LiverCenter

Biomarkers of Liver Injuryin a World without Gold Standards

Thierry Poynard+

AP-HP Groupe Hospitalier Pitié Salpêtrière,UPMC Liver Center, Université Paris 6, INSERM U680, Biopredictive France

jeudi 13 janvier 2011

13 janv. 2011

The «Biopsist»

2 Poynard J Hepatol 2010jeudi 13 janvier 2011

13 janv. 2011

The «Biopsist»

• Still recommends biopsy as the first-line estimate of liver injury


13 janv. 2011

The «Biopsist»


• Agrees that


13 janv. 2011

The «Biopsist»


• Agrees that

• Biopsy is not a perfect gold standard but still believes that it is the best estimate


13 janv. 2011

The «Biopsist»


• Agrees that


• In cases where biopsy is contraindicated, validated biomarkers should be recommended.


13 janv. 2011

The «Biopsist»


• Agrees that



• Biopsy is not recommended for screening of large populations.


13 janv. 2011

The «Biopsist»


• Agrees that




• He rarely admits that in case of discordance between a validated biomarker and a 25 mm biopsy, the biopsy could be a false-positive or a false-negative.


13 janv. 2011

The «Biopsist»


• Agrees that




• He rarely admits that in case of discordance between a validated biomarker and a 25 mm biopsy, the biopsy could be a false-positive or a false-negative.

• He is typically the head of a Pathology unit.


FibroTest ActiTest

If refused or not interpretableBiomarkers

Biopsy first line


13 janv. 2011

The "Biomarkerist"


13 janv. 2011

The "Biomarkerist"

• Recommends validated biomarkers as the first-line estimate of liver injury


13 janv. 2011

The "Biomarkerist"


• Agrees that


13 janv. 2011

The "Biomarkerist"


• Agrees that

• A biomarker is not a perfect test but believes that it is as accurate as a 25 mm long liver biopsy, with the same gray zones.


13 janv. 2011

The "Biomarkerist"


• Agrees that


• In case of discordance between a biomarker and a 25 mm biopsy, he believes that the failure may be due to either the biomarker or the biopsy (50%/50%).


13 janv. 2011

The "Biomarkerist"


• Agrees that



• In order to be useful to clinicians, the biomarker of fibrosis must be available along with those of necrosis and steatosis.


13 janv. 2011

The "Biomarkerist"


• Agrees that




• In case of non-interpretability of the biomarker, another biomarker should be recommended, and then if still not interpretable, a biopsy should be recommended as a third-line assessment.


13 janv. 2011

The "Biomarkerist"


• Agrees that




• In case of non-interpretability of the biomarker, another biomarker should be recommended, and then if still not interpretable, a biopsy should be recommended as a third-line assessment.

• He is typically the inventor of a biomarker.


If not interpretableBiopsy

FibroTest ActiTest

If not interpretableFibroscan

98%

<1%

A la ParisienneFibrotestFirst Line


13 janv. 2011

The «BioCocktailist» (1)


13 janv. 2011


• Recommends biomarker first and then biopsy if the biomarker result is not convincing


13 janv. 2011



• 2 Subtypes:


13 janv. 2011



• 2 Subtypes:

• «Sequentialist»


13 janv. 2011



• 2 Subtypes:


• Starts with one biomarker and recommends biopsy if the result belongs in what he calls a "gray zone"F1/F2


13 janv. 2011



• 2 Subtypes:


• Starts with one biomarker and recommends biopsy if the result belongs in what he calls a "gray zone"F1/F2

• He seems to take the results of the biopsy in the gray zone as the truth without risk of false positive/negative, even with small length (< 25mm) biopsies.


SequentialistFibrotest or FibroScan

First Line

If F1or F2Biopsy

FibroTest ActiTest


Biopsy has the same «Gray Zone»Bedossa Hepatology 2003

25mm Biopsy

F4-F3

25% False Positive

F2-F1

25% False Positive and Negative

F1-F0

25% False Negative


13 janv. 2011

The BioCocktailist (2)


13 janv. 2011


• «Discordantist»


13 janv. 2011



• Performs two biomarkers and recommends biopsy only in case of discordance.


13 janv. 2011




• He finally believes in the result supported by the concordance between one of the biomarkers and biopsy.


13 janv. 2011




• He finally believes in the result supported by the concordance between one of the biomarkers and biopsy.

• The BioCocktailist is typically a friend of one "Biopsist" and two "Biomarkerists".


A la BordelaiseFibrotest and FibroScan

First Line

If discordanceBiopsy

FibroTest ActiTest


13 janv. 2011

Insulin resistance

Alcool consumption

Hepatitis B

Hepatitis C

Hemochromatosis

0 150 300 450 600

No advanced fibrosis Advanced fibrosis

11

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


13 janv. 2011

10 years of claims for diagnostic procedures 1993-2003: Severe Adverse Events and Deaths (French Insurance)

Poynard T. Rev Med Interne 2007


13 janv. 2011


Technic Severe Adverse Events Deaths

ERCP 71 30

Liver Biopsy* 11 5

Ultrasound-Endoscopy 4 2



13 janv. 2011


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



F4

F1

F0

Fibrotic Liver Disease

F2

F3

Hemorrhage Liver failure Cancer

Poynard Lancet 1997


F4

F1

F0


F2

F3


Poynard Lancet 1997

Reassure and follow


F4

F1

F0


F2

F3


Poynard Lancet 1997

Reassure and follow

Prediction of response to treatment

Treatment of the cause


F4

F1

F0


F2

F3


Poynard Lancet 1997

Reassure and follow



Prevention cirrhosis complications


F4

F1

F0


F2

F3


Poynard Lancet 1997

Reassure and follow



Prevention cirrhosis complications

Cost Complications: 50-100 k€


13 janv. 2011

Fibrosis biomarkers: 20 years history

Poynard SJG 2008

n=100

n=500.000


13 janv. 2011

Fibrosis biomarkers: 20 years history

Poynard SJG 2008


FibroTest Fibroscan

Pinzani, Castera Lancet 2010

Validated biomarkers


13 janv. 2011

FibroMAX: HCV-HBV-ALD-NAFLD

17


13 janv. 2011


ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMAX

17


13 janv. 2011

Anticipated Frequently Asked Questions


13 janv. 2011


• Is the perfect fibrosis biomarker possible? No


13 janv. 2011



• There is a "gray zone" or "inaccurate zone" between intermediate stages? No


13 janv. 2011




• Is FibroTest better than non-patented biomarker?: ALT, Forns, APRI... Yes


13 janv. 2011





• Is liver biopsy still useful? Yes


13 janv. 2011






• Same performance of Fibrotest in HCV, HBV, ALD, NAFLD? Yes


13 janv. 2011







• Similar prognostic value of FibroTest vs biopsy? Yes


13 janv. 2011








• Fibrotest-ActiTest-SteatoTest-NashTest-AshTest better than FibroScan? Yes


13 janv. 2011









• Rational of FibroTest components? Yes


13 janv. 2011









• Rational of FibroTest components? Yes

• Are the authors credible due to their possible conflict of interest? Yes


13 janv. 2011

Rational of FibroTest:

Imbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010


13 janv. 2011


• Alpha 2 macroglobulin: key protein for Collagenase metabolism



13 janv. 2011



• Apolipoprotein A1 key protein for Collagen trapping



13 janv. 2011




• Haptoglobin: key protein for binding Free Hemoglobin oxidant



13 janv. 2011





• Total Bilirubin: specific marker of severe late Fibrosis



13 janv. 2011






• Gamma Glutamyl Transpeptidase: sensitive marker of early Fibrosis



13 janv. 2011







• No transaminases: to prevent inflammatory necrosis confusion (ActiTest)



13 janv. 2011








• Proteomic has blindly proved the major diagnostic value of



13 janv. 2011









• Apolipoprotein A, A2M



13 janv. 2011









• Apolipoprotein A, A2M

• HaptoglobinImbert Bismut 2001, Langlois 2006, Watanabe 2009, Ho 2010


13 janv. 2011

Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI


13 janv. 2011

Imbert-Bismut, Lancet 2001jeudi 13 janvier 2011

13 janv. 2011

In Situ


13 janv. 2011

In Situ In Serum: FibroTest


13 janv. 2011


Imbert-Bismut, Lancet 2001

Liver Injury

Activated Stellate Cells

Fibrotic Matrix


13 janv. 2011

Alpha2Macroglobulin



Liver Injury


Fibrotic Matrix


13 janv. 2011

Alpha2Macroglobulin

Total Bilirubin



Liver Injury


Fibrotic Matrix


13 janv. 2011

Alpha2Macroglobulin

Total Bilirubin

Gamma GT



Liver Injury


Fibrotic Matrix


13 janv. 2011

Haptoglobin

Alpha2Macroglobulin

Total Bilirubin

Gamma GT



Liver Injury


Fibrotic Matrix


13 janv. 2011

Haptoglobin

Alpha2Macroglobulin

Apolipoprotein A1

Total Bilirubin

Gamma GT



Liver Injury


Fibrotic Matrix


13 janv. 2011

In Situ events: Fibrosis and serum ApoA1 decrease

Apo A1

Trapping

Down Regulation

Paradis Cell Mol Biol 1996, Paradis Hepatology 1996, Mathurin Hepatology 1996.


13 janv. 2011

Haptoglobin Hemopexin


13 janv. 2011


13 janv. 2011

• 38 Published Studies

• 7.985 Patients

• Standardized AUROC

• 0.84 (0.83-0.86)

• Advanced Fibrosis

Halfon et al GCB 2008

The best you can obtain with

20mm biopsy is 0.90 Bedossa 2003

FibroTest accuracy for the diagnosis of advanced fibrosis


13 janv. 2011Kinetics of fibrosis according to baseline stagesIn HBV patients treated with lamivudine 2 years

n=283

F0F1 NS

F2F3F4 P=0.01

0.00

0.25

0.50

0.75

1.00

Baseline 6 mo 12 mo 24 mo

FibroTest-FibroSURE

44 Cirrhosis: 42 (95%) improvement at 24 months; Significant regression (>0.30) in 14/44 (32%)

0.73

0.52

Dienstag et al Gastroenterol 2003. Poynard et al Am J G 2005


13 janv. 2011

A New simple definition of low risk patients

Ngo PlosONE 2008


13 janv. 2011

A New simple definition of HBV Inactive Carrier

FibroTest<= 0.27 ActiTest <= 0.29

+

Ngo PlosONE 2008

Viral Load < Log5


13 janv. 2011

Survival according to definition of inactive carrier based on FibroTest-ActiTest normal values in untreated patients

FibroTest and ActiTest

Survival without complications

Survival without death Overall Survival Survival Paired

Controls**

Normaln=289 100% 100% 100% 99.6 %

(99.5-99.6)

Not normaln=208*

91.2 % (84.2-98.1)

94.7 % (89.7-99.8)

91.2 % (84.2-98.1)

98.4 % (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


13 janv. 2011

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

30


13 janv. 2011

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

0.00

0.33

0.67

1.00

F0 F1 F2 F3 F4

Fibr

otes

t

BloodDonors

Poynard Clin Chem 2004, Comp Hepatol 2004jeudi 13 janvier 2011

13 janv. 2011

32

Validated Fibrosis and Activity Biomarkers 500.000 prescriptions in 35 countriesUsed by 80% of French Hepatologists, first line

FibroTest ActiTest

Castera J Hepatol 2007


13 janv. 2011

F0

Pas de Fibrose


13 janv. 2011

F1

Fibrose minime


13 janv. 2011

F2

Fibrose modérée


13 janv. 2011

F3

Fibrose importante


13 janv. 2011

F4

Fibrose sévère


13 janv. 2011

FibroTest prognostic value among HCV cirrhosis stage1,457 patients followed 5 years

De Ledhingen EASL 2010


HCV Survival according to FibroTest classes

N=537 NGO Clin Chem 2006, Ngo Clin Chem 2008


13 janv. 2011

AUROCsFibroTest 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

5 year Prognostic Value of FibroTest versus Biopsy Fibrosis Staging Survival Without HCV Complications

N=537 NGO Clin Chem 2006

40


13 janv. 2011

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

41


13 janv. 2011

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

42


13 janv. 2011ActiTest 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 comparisons


13 janv. 2011ActiTest 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 comparisons


High Risk False Positive Negative

5/954 (0.52%)


38/7494 (0.51%)

FibroTest Global Quality Estimates

High Risk False Positive Negative3349/345,695 (0.97%)


491/24,872 (1.97%)

FibroScan (Roulot et al 2008)>7.1 kPa= 12.6%: False Positives ?

Poynard EASL 2010, Roulot J Hepatol 2008


13 janv. 2011

Three high-risk populations for false positive/negative

• Tertiary center: 1.97%

• HIV co-infection: 1.77%

• Sub-Saharan origin: 2.61%

45


Pro

SimpleBloodAccurate for F0F1F2F3F4

Cons

Applicability 98% (Hemolysis)Precautions of use

FibroTest


Première Ligne (99%)

Deuxième Lignesi risque FP/FN (1%)

Troisième Lignesi discordance


13 janv. 2011

• 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

49

Elastography


13 janv. 2011

Oliveri WJG 2008


13 janv. 2011

Pitfalls of Fibroscan

3.1% Failures and Unreliable results 15.8%


13 janv. 2011

Choice of FibroScan Cutoffs

Castera 2005, Ketanneh 2007Roulot 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


13 janv. 2011

HCV n=92Mean Fibrotest and Actitest

0

0,20

0,40

0,60

0,80

1,00

FibrotestActitest

Baseline 12 weeks 24 weeks 48 weeks

D’Arondel et al JVH 2006

Fibrosis Activity


13 janv. 2011

HCV n=416Median % changes Fibrosis estimates (12-24 month)

-30%

-25%

-20%

-15%

-10%

-5%

0%

5%

10%

Control (n=304)NR (n=27)

SVR (n=70)

FibroTest Fibroscan

Vergniol et al JVH 2009


13 janv. 2011

HCV n=416Mean FibroTest (range 0.00-1.00)

0

0,12

0,24

0,36

0,48

0,60

Control (n=304)SVR (n=70)

Baseline 12mo/EOT 24mo/EOF


Slow increase = Sensitivity

Slow decrease = Not related to activity


13 janv. 2011

HCV n=416Mean Liver Stiffness Measurements (range 0-75 kPa )

0

3

6

9

12

15

Control (n=304)SVR (n=70)

Baseline 12mo/EOT 24mo/EOF


Too Early = necro-inflammatory activity

improvement ?

No treatment No increase = Lack of sensitivity ?


13 janv. 2011

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


13 janv. 2011

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 Standard

Bedossa Hepatology 2003, Poynard Clin Chem 2005, Poynard Clin Chem 2007, Poynard GCB 2008


13 janv. 2011


13 janv. 2011

Bedossa Hepatology 2003


13 janv. 2011


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


13 janv. 2011


AUROC 5 mm = 0.75AUROC 15 mm = 0.82AUROC 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”


13 janv. 2011

T Poynard, F Charlotte, G LeNahour, M Munteanu


13 janv. 2011

Gold-validation of liver fibrosis estimates, FibroTest (FT) and liver stiffness measurement (LSM), using surgical samples and virtual biopsies

T Poynard, F Charlotte, G LeNahour, M Munteanu


13 janv. 2011

Virtual biopsy Digitized image (Aperio Scanner, TRIBVN, France)

Increasing length 5/10/15/20/25/30mm


13 janv. 2011


22,119 virtual biopsiesIncreasing length 5/10/15/20/25/30mm


13 janv. 2011


22,119 virtual biopsies18 operated subjects



13 janv. 2011



•5,106 HCV



13 janv. 2011



•5,106 HCV •4,572 ALD



13 janv. 2011



•5,106 HCV •4,572 ALD •3,240 NAFLD



13 janv. 2011



•5,106 HCV •4,572 ALD •3,240 NAFLD •2,988 HBV



13 janv. 2011



•5,106 HCV •4,572 ALD •3,240 NAFLD •2,988 HBV •1,548 PBC



13 janv. 2011



•5,106 HCV •4,572 ALD •3,240 NAFLD •2,988 HBV •1,548 PBC

•4,665 controls



13 janv. 2011

METAVIR Stage

Nb virtual biopsies

Area Fibrosis by

Image Analysis

Fibrotest LSM

Mean (95%CI)

F0 780 3.8 (3.5-4.0) 0.00-0.27 0.0-5.0

F1 137 5.0 (4.5-5.3) 0.28-0.48 5.1-8.8

F2 768 7.1 (8.0-8.5) 0.49-0.58 8.9-12.0

F3 270 9.1 (7.9-10.1) 0.59-0.74 12.1-14.5

F4 1734 18.2 (16.5-17.6) 0.75-1.00 14.6-75.0


13 janv. 2011


64


13 janv. 2011


ActiTest


AshTest

NashTest

FibroMAX

64


13 janv. 2011

SteatoTest for Steatosis744 patients 140 controls

SteatoTestGGT AUROC=0.66

ALT AUROC=0.61

AUROC=0.80

Poynard Comp Hepatol 2005


13 janv. 2011

LiverCenter

HCV-GenoFibroTest

A better prediction of virological response


13 janv. 2011


13 janv. 2011


68


13 janv. 2011


ActiTest


AshTest

NashTest

FibroMAX

68


13 janv. 2011

HCV-GenoFibroTest: Liver injury, Virus Resistance, Host Genes for treatment Response and Tolerance

69

ActiTest


IL28B

HCV-GenoFibroTest

Viral Load

Viral Resistance

ITPA

UGT1A1

Genotype


13 janv. 2011

LiverCenter

IL28b, ITPA, UGT1A1 and prognostic factors of treatment response in patients with chronic hepatitis C

Jean Marc Costa, Mona Munteanu, Yen Ngo, Vincent Thibault, Moussalli Joseph, Vlad Ratziu, Yves Benhamou, Jean Dominique Poveda and Thierry Poynard.

Clinics and Research in Hepatology and Gastroenterology, 2011


13 janv. 2011

Sustained Virologic Response (SVR)

0

25

50

75

100

47%63%

SVR

Training Validation

• Independent Factors (OR; P value)

• Genotype 2/3 (5.7 <0.0001)

• IL28B CC (4.8 <0.0001)

• FibroTest low (4.2 0.03)

• ActiTest high (3.9 0.03)

• Viral load <5.8 Log (1.9 0.03)

Costa CRHG 2011


13 janv. 2011

AUROCs for SVR

Training population = 0.743 (0.655-0.810; P<0.0001 vs random), not different (P=0.88)

than Validation population = 0.753 (0.616-849; P=0.0007 vs random).

Costa CRHG 2011


13 janv. 2011

Sustained Virologic Response according to HCV-GenoFibroTest Score

0%

25%

50%

75%

100%

SV

R

19%44% 61%

94%

0-0.25 (n=42)0.25-0.50 (n=90)

0.50-0.75 (n=69)0.75-1 (n=35)

HCV-GenoFibroTest Score Costa CRHG 2011


BioPredictive S.A.S - Capital social 40.000 Euros - SIRET 442349387 00013 - Code APE 7219Z - Numero TVA intracommunautaire FR00442349387

http://www.biopredictive.com/

HCV Geno-FibroTestInternal reference : TEST

Ref #123456

Patient

Birth date 1935-09-22

Sex Female

IL28B Genotype C/C

Biomarkers

Sample date 2009-05-06

Alpha2Macroglobulin 3.12 g/l

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

Hepatitis C

HCV Viral Load 250000

HCV Genotype Genotype 2

Tests resultsFibroTest ActiTest HCV Geno-FibroTest

FibroTest assesses thefibrosis of the liver

ActiTest assesses activity(inflammation in chronic

viral hepatitis C or B)

Chance of sustainedvirological response.

Score: 0.72(F3)

Score: 0.41(A1-A2)

Score: 0.14(SVR ++)

F3: advanced fibrosis A1-A2: minimal activity SVR ++: very goodresponse

Precautions of use and interpretabilityÅ 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 Gilbert's 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 flawin the biopsy: i.e. a liver biopsy has a 33% variability rate for one fibrosis stageÅ 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.


13 janv. 2011

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

75


F4

F1

F0

France: 12,000,000 at Risk100%

5%

Death 15,000/year0.1%

Biomarker10% F2

F3


biomarkers of liver injury.pdf

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