FibroTest in the diagnosis of HBV Publications on diagnostic performance FT in diagnostic of HBV

In this Presentation 1. Diagnosis and clinical options 2. First validation of FibroTest-ActiTest in HBV 3. FibroTest in histological changes 4. FibroTest, combinations and comparison with other non invasive methods 5. Meta-analysis FT in diagnostic of HBV

Diagnosis and clinical options Positive serology FT in diagnostic of HBV Poynard et al, Comp Hepatol 2004

First HBV validation FT in diagnostic of HBV

Myers RP et al, J Hepatol 2003 – First Validation in HBV Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B (n=209) Conclusions Sensibility analyse: markers nt affected by ethnicity, HBV DNA or HBV status In AgHbe positive patients: FT more accurate than AST (AUROC: 0,89 vs 0,79 AST vs METAVIR Inflammation grade ActiTest vs METAVIR Inflammation grade FibroTest : useful for identification of HBV-related fibrosis ActiTest: useful for excluding significant necroinflammation AST vs METAVIR Fibrosis stage ActiTest vs METAVIR Fibrosis stage FT in diagnostic of HBV

FibroTest in Histological changes FT in diagnostic of HBV

Poynard et al, Am J of hepatology 2005 Longitudinal Assessment of Histology Surrogate Markers (FibroTest–ActiTest) During Lamivudine Therapy in Patients with Chronic Hepatitis B Infection Conclusion In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT–AT should be useful in the noninvasive follow-up of lamivudine treatment. AUROC of FirboTest ActiTest =: 0,74-077, similar as the one observed in patients with HCV FT in diagnostic of HBV

Poynard et al Am J G 2005 0.73 0.52 Conclusion Kinetics of fibrosis according to baseline stages in HBV patients treated with lamivudine 2 years (n=283) 0.00 0.25 0.50 0.75 1.00 Baseline 6 mo 12 mo 24 mo FibroTest 0.73 0.52 Conclusion 44 Cirrhosis: 42 (95%) improvement at 24 months Significant regression (>0.30) in 14/44 (32%) F2F3F4 P=0.01 F0F1 NS FT in diagnostic of HBV

Poynard et al, AASLD 2007 Impact of adefovir dipivoxil on liver fibrosis and activity assessed with biochemical markers (FibroTest-ActiTest) in patients infected by Hepatitis B Virus Study group Chronic hepatitis B (HBeAg+ and HBeAg-) Randomized in two placebo-controlled trials of ADV Available paired liver biopsies and FibroTest-ActiTest at baseline and after 48 weeks of treatment Liver biopsies scored for fibrosis and inflammation, utilizing Knodell, Ishak and METAVIR scoring systems, one blinded central pathologist Methods AUROCs for the diagnosis of advanced fibrosis, cirrhosis, and moderate-severe activity Sensitivity analyses: ethnicity, biopsy size, HBeAg status Impact of treatment assessed on liver injury (biopsy and FibroTest-ActiTest) according to baseline stage, and virological response Analysis of discordance between biopsy and FibroTest FT in diagnostic of HBV Poynard et al, AASLD 2007

Poynard et al, AASLD 2007 - Results FibroTest and Fibrosis Stages Ishak Stages METAVIR stage FT in diagnostic of HBV

Poynard et al, AASLD 2007 - Results ActiTest and Necro-Inflammatory Features Peri Portal Necrosis Knodell Score Lobular necrosis Knodell Score Portal Inflammation Knodell Score FT in diagnostic of HBV

Poynard et al, AASLD 2007 - Results ActiTest and Necro-Inflammatory Scoring System Ishak Activity grade METAVIR Activity grade FT in diagnostic of HBV

Poynard et al, AASLD 2007 - Results Impact of HBV treatment on fibrosis: Biopsy versus FibroTest 48 weeks with adefovir (n=304) or placebo (n=158) Biopsy FibroTest P<0.0001 P<0.0001 FT in diagnostic of HBV

Poynard et al, AASLD 2007 - Results Impact of HBV treatment on fibrosis in HBV Virological Responders with advanced baseline fibrosis 97 treated with adefovir, 9 treated with placebo (spontaneous clearance) Biopsy FibroTest P<0.0001 P<0.0001 P=0.02 FT in diagnostic of HBV

Poynard et al, AASLD 2007 - Conclusions Discordance analysis 29% discordances estimated by the classical analysis considering biopsy as the gold standard 29 discordant cases had incoherence between virological response and histological response Failure attributable to biopsy 66% (19/29) false positive median 11mm, false negative median 7-mm Failure attributable to FT-AT 34% (10/29) If these estimates are true the real rates of patients misclassified using FT-AT is 10% (34% of 29%) Conclusions Provides an accurate quantitative estimate of liver fibrosis and necro-inflammatory activity Is effective and very sensitive as noninvasive marker of histological changes during treatment or followup without treatment FT in diagnostic of HBV

Combination and comparison with other non invasive methods FibroScan, APRI, Mp3 FT in diagnostic of HBV

Sebastiani et al, J Hepatol 2006 Diagnostic performance of non-invasive biomarkers of liver fibrosis in chronic hepatitis B (n=110) Results Diagnosis of F2F3F4 & F4 Se: 89,5% & 62,5% Sp: 78,8% & 98,4% NPV: 64,7% & 95,4% PPV (for F4): 83% FibroTest correctly classfied all patients Conclusions Fibrotest presents with the best accuracy in all the subgroups of patients with chronic liver disease Combination of markers should reduce the need for liver biopsy HEPATITIS B (AUC) APRI FIBROTEST 0.72 0.85 0.64 0.76 >F2 F4 FT in diagnostic of HBV

Sebastiani et al, J Hepatol 2006 – Safe Biopsy Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY) Stepwise modelling aimed to achive accuracy> 95% For significant fibrosis For cirrhosis FT in diagnostic of HBV

Sebastiani et al, J Hepatol 2006 – Safe Biopsy Sequential Algorithms for Fibrosis Evaluation (SAFE BIOPSY) INTERIM ANALYSIS ON 210 HBV CASES SAFE BIOPSY for SIGNIFICANT FIBROSIS SAFE BIOPSY for CIRRHOSIS Accuracy (%) 96 90 Saved biopsies (%) 45 77 Saved cost (%) 44 75 FT in diagnostic of HBV

Castera L. et al, J Hepatol 2006 Prospective comparison in FibroScan (FS) and FibroTest (FT) in inactive hepatitis B carriers Study Group Cohort of 154 HBV patients, among these 40 inactive carriers Method FibroTest and FibroScan given the same day Results Fibroscan Failure: 6 Median value (FS and FT) significantly lower in inactive carriers than in other patients Agreement of FS and FT for the absence of significant fibrosis in 83% of the patients Conclusion Non invasive assessment of fibrosis in HBV inactive carriers per FT and FS could be useful FT in diagnostic of HBV

Hilleret et al, J Hepatol 2006 Diagnostic accuracy of mp3 score compared to hyaluronate and FibroTest for evaluating liver fibrosis in chronic hepatitis B Diagnostic accuracy evaluated by AUROC for discriminating F0F1F2 vs F3F4 HA MP3 FT Comments MP3 score greater than 0.50 had a PPV for extensive fibrosis of 82%, while score lower than 0.30 had a NPV of 88%. When combining MP3 (0.40) and HA (80), the PPV increased to 92% for F3F4 0.82 0.81 Conclusions MP3, HA and FT have a good accuracy in HBV infection in predicting extensive fibrosis, especially when used in combination. Especially useful for of inactive carriers who might have cirrhosis. FT in diagnostic of HBV

Meta analysis FT in diagnostic of HBV

FibroTest Meta-Analysis Poynard et al, clin chem 2007 FibroTest Meta-Analysis 30 Published Studies 6.378 Patients 2001-2006 AUROC=0.84 (0.83-0.86) for F2F3F4 The best you can obtain with 20mm biopsy is 0.90 Bedossa 2003 FT in diagnostic of HBV