Paul Calès Conflict of interest: FibroMeter Case report Paul Calès Conflict of interest: FibroMeter

October 2001: HCV serology  January 2002: Man, 45 year old in 2001 October 2001: HCV serology  January 2002: AST: 69, ALT: 121 UI/l HCV RNA  HCV genotype: 4c/4d

15/3/02 Liver biopsy: 2 fragments: 12 mm x 2 Metavir: A2 F2

January and September 2003: HVC RNA : responder October 2002: IFN 150 µg x 3/w + RIBA 1 g/d for 1 year January and September 2003: HVC RNA : responder

2004: HCV RNA : relapser 2004-7: No treatment for HCV follow-up:

Follow-up by non-invasive tests Fibroscan M (IQR) (kPa) FibroMeter InflaMeter 24/06/04 7.7 0.65 18/10/05 6.3 0.69 10/10/06 0.78 0.81 13/11/07 6.4 (0.6) 0.67

Fibroscan interpretation Meta-analysis of Tsochatzis et al (J Hepatol 2011;54:650-9). Patient: F0/1 Metavir kPa F0/1 ≤ 7.2 F2 7.3 ≤ FS ≤ 10.1 F3 10.2 ≤ FS ≤ 14.9 F4 ≥ 15.0

FibroMeter interpretation Boursier J, BMC Gastroenterol 2011 Patient: F2±1

Questions (1) What is your diagnosis for fibrosis staging? What to do?

10/4/08 HCV RNA: 5.1 Log UI/ml AST: 39, ALT: 66 UI/ml Liver biopsy: 2 fragments: 3 mm x 2 Metavir A2/3 F2/3

Questions (2) What is your diagnosis for fibrosis staging? What to do?

Liver biopsy under US guidance: 17/6/08 Liver biopsy under US guidance: 2 fragments: 7 & 20 mm Double reading: Metavir: A2 F2 Ishak: grade 7, stage 2

Inclusion in the ANRS study HC 29 Irbesartan vs placebo for 2 years in Metavir F2 or F3 HCV pts who refuse or have contra-indication or no indication to SOC treatment (IFN + Riba).

23/9/10 Liver biopsy: 1 fragment: 39 mm Double reading: Metavir: A2 F2 Ishak: grade 6, stage 3

Overview on follow-up of liver lesions Fibroscan M (IQR) (kPa) FibroMeter CombiMeter CirrhoMeter InflaMeter Metavir 15/03/02 A2 F2 24/06/04 7.7 0.65 18/10/05 6.3 0.69 10/10/06 0.78 0.81 13/11/07 6.4 (0.6) 0.67 10/04/08 6.9 (0.04) 15/09/09 5.8 (0.09) 23/09/10 7.7 (2.6) 13/12/11 5.6 (0.9) 0.70 (F2±1) 0.53 (F2±1) 0.14 0.57

Follow-up: results of non-invasive markers

Dynamic sensitivity of tests in natural history of hepatitis C FibroMeter Fibroscan Year 3 vs year 1: p<10-3 Year 3 vs year 1: p=0.410 Calès, Clin Biochem 2010

Dynamic reproducibility of tests in natural history of hepatitis C FibroMeter Fibroscan Year 3 vs 1 ric=0.83 Year 3 vs 1 ric=0.44 Calès, Clin Biochem 2010

Dynamic reproducibility (2 years) of mesures of liver lesions Fibrosis Activity Histological mesure Blood test Calès, J Viral Hepatitis 2012

Comparaison of liver histology, morphometry and blood tests to assess fibrosis progression 101 pts with HCV±HIV Follow-up: 96 w Histology Blood tests * The area of fibrosis was the sole histological characteristic with a significant change (%). * CirrhoMeter was the only blood test with a significantly higher change than that of area of fibrosis (p=0.039). * CirrhoMeter Area of fibrosis Calès, J Viral Hepatitis 2012 * : significant change 20

a b c d P = 0.003 P = 0.020 From Calès, J Viral Hepatitis 2012 ric = 0.815 ric = 0.826 c d

Agreement between biopsies Résultats 5 Fibrosistop.spo From Calès, J Viral Hepatitis 2012

Conclusion Considering non-invasive tests in HCV hepatitis, blood test and elastometry have the advantage to be independent methods. In case of discrepant results, two solutions: Another third examination like liver biopsy Or test combination For follow-up, certain blood test(s) could be more reproducible and more sensitive to detect small changes than other examinations.

BU

CombiMeter: FibroMeter + Fibroscan New tests 1 0 CirrhoMeter Accuracy: 87% CombiMeter: FibroMeter + Fibroscan Accuracy: 92% Boursier EJGH 2009 Boursier Hepatology 2012