FT in diagnostic of HBV FibroMax in the most common liver diseases FibroMax: a universal biomarker of liver disease.

FibroMax in the most common liver diseasesFibroMax in the most common liver diseases

FibroMax: a universal biomarker of liver disease

1.1. What is FibroMax?What is FibroMax?

2.2. FibroMax in Viral Hepatitis: FibroTest-ActiTestFibroMax in Viral Hepatitis: FibroTest-ActiTest

3.3. FibroMax in Steatosis: SteatoTestFibroMax in Steatosis: SteatoTest

4.4. FibroMax in non alcoholic steato-hepatitis: NashTestFibroMax in non alcoholic steato-hepatitis: NashTest

5.5. FibroMax in alcoholic steato hepatitis: AshTestFibroMax in alcoholic steato hepatitis: AshTest

6.6. Meta-analysisMeta-analysis

In this PresentationIn this Presentation

• 5 tests together to assess liver injuries in HBV, HCV, NAFLD, ALD

What is FibroMax?What is FibroMax?

Patient Profile

ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMaxFibroMax

For Fibrosis

For Viral activity

For NASH activity

For ASH activity

For Steatosis

FibroMax in Viral HepatitisFibroMax in Viral Hepatitis

FibroTest-ActiTest presentation

ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMaxFibroMax

For Fibrosis

For Viral activity

For NASH activity

For ASH activity

For Steatosis

FibroMax in viral hepatitis B and CFibroMax in viral hepatitis B and C

• For more information please report to following presentations– FibroTest in the diagnosis of HBV, FibroTest: prognostic value in HBV , FibroTest in the diagnosis of

HCV, FibroTest: prognostic value in HCV

Presentations available on www.oneliver.com

• Relationship between FibroTest and the stage of firbosis and between ActiTest and the grade of Activity

FibroMax in SteatosisFibroMax in Steatosis

SteatoTest Presentation

ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMaxFibroMax

For Fibrosis

For Viral activity

For NASH activity

For ASH activity

For Steatosis

Bellentani, Dionysos Study, J Hepatol 2001

Population at risk of liver steatosis (Millions)Population at risk of liver steatosis (Millions)

FibroMaxFibroMax

+ Age, Gender

Haptoglobin

Alpha2Macroglobulin

Apolipoprotein A1

Total Bilirubin

Gamma GT

FibroTestFibroTest

Glucose

ALT

Cholesterol

AST

Triglycerides

+ Weight, Height

Biomarker activity in steatosisBiomarker activity in steatosis

Poynard Comp Hepatol 2005Poynard Comp Hepatol 2005

• The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis

Included Patients

Validation group 1 HCV before treatment N=310

Validation group 2 HCV sustained responders

N=201

quasi-normal characteristics with normal liver tests

only 11% grade 2–4 steatosis.

Validation group 3 Alcoholic liver disease N=62

more often male, older, had smaller liver biopsies,

more metabolic risk factors, more extensive fibrosis more grades 2–4 steatosis

Control group Healthy blood donors N=140

Patients included in the 4 groups similar in age with predominance of male subjects (range 61–76%). The prevalence of steatosis greater than 5% (grades 2 to 4) varied from 11% in hepatitis C virus (HCV)

cured patients to 94% in patients with ALD. In all groups, at least one metabolic risk factor was observed in more than 50% of included patients.

SteatoTest versus GGT and ALTSteatoTest versus GGT and ALTPoynard Comp Hepatol 2005Poynard Comp Hepatol 2005

• Relationship between ST, GGT and ALT and the grade of liver steatosis in the 3 validation groups

Validation group 1

SteatoTest GGT ALT

Validation group 2

SteatoTest GGT ALT

Validation group 3

SteatoTest GGT ALT

SteatoTest versus GGT and ALTSteatoTest versus GGT and ALTPoynard Comp Hepatol 2005Poynard Comp Hepatol 2005

• Relationship between ST, GGT and ALT and the grade of liver steatosis in the integrated database combining controls, training group and validation groups

AUROC=0.80 AUROC=0.66 AUROC=0.61SteatoTest GGT ALT

SteatoTest UltraSonography Significance

Kappa 0.44 ± 0.06 0.32 ± 0.05 0.02

AUROC 0.78 ± 0.03 0.65 ± 0.03 0.001

SteatoTest versus UltraSonographyPoynard et al, Comp Hepato 2005

• Biopsy as Gold Standard n=304

FibroMax in FibroMax in Non Alcoholic Steato-HepatitisNon Alcoholic Steato-Hepatitis

NashTest

ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMaxFibroMax

For Fibrosis

For Viral activity

For NASH activity

For ASH activity

For Steatosis

NashTest: AUROCNashTest: AUROCPoynard et al, BMC Gastro 2006Poynard et al, BMC Gastro 2006

NashTest for NASH ROC for Kleiner Class NashTest for NASH 124 validation cases of CYTOL prospective study

• AUROC NASH = 0.83 (SE=0.04)

-- Nash-- Borderline Nash-- No Nash

NashTest versus BiopsyNashTest versus Biopsy- Poynard et al BMC Gastro 2006- Poynard et al BMC Gastro 2006

• Concordance between NASH predicted by NashTest and predicted by biopsy (in all patients n=257)

BiopsyNT

No Nash Borderline Nash Nash

No Nash 49 11 8

Borderline Nash 46 77 34

Nash 3 8 21

Kappa Statistic 0.33―0.04

Discordance 1 class 99/257=39%

Discordance 2 classes 11/257=4%

NashTest versus BiopsyNashTest versus Biopsy- Poynard et al BMC Gastro 2006- Poynard et al BMC Gastro 2006

• Sensitivity, Specificity and predictive values of NashTest for the diagnosis of NASH (in all patients n=257)

Sensitivity Specificity PPV NPV

No Nash 33% 94% 66%Prevalence= 0.25

81%

Borderline Nash or Nash 88% 50% 74%

Prevalence=0.6272%

Conclusion• In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker

reliably predicts the presence or absence of NASH.

• Among patients with NAFLD, the new generation of biomarkers such as FibroTest, SteatoTest and NashTest will allow better identification of those at risk and reassurance for patients without fibrosis or NASH.

• Biomarkers as a first-line estimate of injury in chronic liver diseases should reduce the need for liver biopsy

Proposed screening strategy of advanced fibrosis, steatosis and NASH in NAFLD patients.

FibroMax in Alcoholic Steato-HepatitisFibroMax in Alcoholic Steato-Hepatitis

AshTest

ActiTest

FibroTest SteatoTest

AshTest

NashTest

FibroMaxFibroMax

For Fibrosis

For Viral activity

For NASH activity

For ASH activity

For Steatosis

AshTest versus AST/ALT and MaddreyAshTest versus AST/ALT and MaddreyThabut et al, J Hepatol 2006Thabut et al, J Hepatol 2006

• Diagnostic values of AshTest, Maddrey and AST/ALT ratio for the diagnosis of alcoholic hepatitis (225 patients 299 controls)

AshTest AUROC=0.89 AST/ALT AUROC=0.78 Maddrey AUROC=0.78

AshTest versus AST/ALT and MaddreyAshTest versus AST/ALT and MaddreyThabut et al, J Hepatol 2006Thabut et al, J Hepatol 2006

• ROC curves of AshTest, Maddrey and AST/ALT ratio for the diagnosis of alcoholic hepatitis (n=225).

Conclusions Conclusions

In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis.

The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.

AshTest

Maddrey

AST/ALT

Proposed screening strategy of severe alcoholic steatohepatitis (ASH) in excessive drinkers

• ASH screening and treatment strategy

Proposed screening strategy of severe alcoholic steatohepatitis (ASH) in excessive drinkers

• Fibrosis screening strategy in ALD patient