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Non-invasive diagnosis of liver fibrosis in HCV patients

Non-invasive diagnosis of liver fibrosis in HCV patients. Victor de Lédinghen MD PhD CHU Bordeaux France Paris January 2012. Which method: blood sample or liver stiffness?. Hepascore Fibrotest Fibrometer. Liver stiffness ( FibroScan ). False positive or negative.

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Non-invasive diagnosis of liver fibrosis in HCV patients

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  1. Non-invasive diagnosis of liver fibrosis in HCV patients Victor de Lédinghen MD PhD CHU Bordeaux France Paris January 2012

  2. Which method: blood sample or liver stiffness? • Hepascore • Fibrotest • Fibrometer • Liverstiffness (FibroScan)

  3. False positive or negative • Utilize non specific serum biochemical markers • Alpha-2 macroglobulin • Haptoglobin • Gamma-glutamyl transpeptidase • Total bilirubin • Apolipoprotein A1 • Urea • Platelet count • Prothrombin time • Hyaluronate • AST • Acute flare? • Hemolysis? • Gilbert’s syndrome?

  4. FibroScan examination The probe induces an elastic wave through the liver The velocity of the wave is evaluated in a region located from 2.5 to 6.5 cm below the skin surface 25 to 65 mm

  5. Liver stiffness Portal fibrosis Cholestasis Centrolobular fibrosis Stiffness Sinusoidal fibrosis Steatosis? Portal blood flow Inflammation 5

  6. Cut-offs for the diagnosis of cirrhosis Ganne-Carrié N et al. Hepatology 2006;44:1511-7 Vergara S et al. Clin Inf Dis2007;45:969-74

  7. Combination of FibroScan and blood test: well-classified patients and theoretically avoided liver biopsies Zarski JP, et al. J Hepatol 2012; 56:55-62

  8. Combination of tests: well-classified patients and theoretically avoided liver biopsies LB 70.8% LB 49.8% Boursier, Hy 2012

  9. FibroScan and severity of cirrhosis 15 75 kPa 27.5 37.5 49 54 63 Liver stiffness No EV stage 2/3 No Child-Pugh B or C No pasthistory of ascites No hepatocellularcarcinoma No varicealbleeding EV: esophageal varices Foucher J, et al. Gut 2006;55:403–8

  10. Liver stiffness and hepatocellular carcinoma • 866 patients with HCV infection, 3-year follow up • Hepatocellular carcinoma during follow-up: 77 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Cumulative incidence 0 1 2 3 Years after enrolment No. at risk ≤10 kPa 511 501 476 427 10.1–15 kPa 142 130 111 94 15.1–20 kPa 79 76 63 51 20.1–25 kPa 47 41 36 29 >25 kPa 87 75 54 41 Masuzaki R, et al. Hepatology 2009;49:1954–61

  11. Liver stiffness and survival in HCV patients • 1457 HCV patients; follow-up 5 years • Overall survival: 91.7% Fibrotest FibroScan Vergniol J, et al. Gastroenterology 2011;140:1970–9

  12. CONCLUSIONIn clinical practice • Interpretation of methods always by an expert according to clinical context • Quality criteria of FibroScan, (IQR, 10 values) • Quality criteria for biomarkers (hemolysis…) • Combination of methods if needed • Repeat methods if discordant results or liver biopsy • Useful for diagnosis, follow-up, prognosis

  13. Today: useful with other parameters Clinical signs Blood sample Biomarkers Liver biopsy Stiffness Imaging(US, MRI, endoscopy)

  14. Case report

  15. Female 60 years • 60 kg 1.63 m • No diabetes, no hypertension • No alcohol, no tobacco • HCV genotype 1b • IL28B : CT • 25 october 2000 : liver biopsy A2F3 • Treatment with pegylated interferon and ribavirin during 6 months in 2001 : no response.

  16. 2003 New evaluation • ALT 40 IU/L • AST 38 IU/L • Platelet count 17O G/L • Fibroscan 25.5 kPa • Fibrotest 0.48 • Hepascore 0.60 • Just to remind : A2F3 in 2000

  17. Question #1 • There is a cirrhosis • There is no cirrhosis • I don’t know

  18. In 2003 • Fibroscan 25.5 kPa but IQR 29.2 kPa … • Endoscopy : no oesophageal varices • Ultrasonography : no HCC

  19. Reproducibility of FibroScan Inter-observers concordance 0.93 – 0.98 Factors associated with reproducibility High value IQR/M < 0.25 BMI < 25 kg/m² Fraquelli M et al. Gut 2007;56:968-73 Boursier J et al. Clin Gastroenterol Hepatol 2008;6:1263-9

  20. Median value IQR < 21 - 30% of median value Number of measurements ~ 10 Interpretation of FibroScan Lucidarme D, de Lédinghen V. Hepatology 2009;49:1083-9.

  21. Follow-up using FibroScan

  22. 2009 • Platelet count: 190 G/L • PT: 100% • AST 61 IU/L • ALT 68 IU/L • FibroScan : 20.2 kPa (IQR 6.5 kPa) • FibroTest : 0.62 • Hepascore: 1.00

  23. Question #2 • There is a cirrhosis • There is no cirrhosis • I don’t know

  24. 2009 • Liver biopsy : A3F4 • No varices and no HCC • 2010 • Liver stiffness 21.1 kPa (IQR 2.5) • Fibrotest 0.73

  25. 2011. To treat or not to treat? • Female 70 years genotype 1b • Compensated cirrhosis • No portal hypertension • No HCC • No response to previous treatment using PEG-RIBA

  26. Question #3 • I treat using PEG + RIBA + Boceprevir • I treat using PEG + RIBA + Telaprevir • I wait for new drugs • I don’t want to treat: she is 70 years old.

  27. 2011 • 2 March 2011 : treatment started • Pegylated interferon • Ribavirin • Telaprevir

  28. HCV-RNA follow-up in 2011 IU/ml PEG RIBA TELA PEG RIBA

  29. 2012 • End of treatment : end of february • HCV-RNA should be negative • New non-invasive evaluation at the end of treatment.

  30. At the end of treatment, what do you expect? • No change of liver stiffness • Decrease of liver stiffness • Increase of liver stiffness

  31. Follow-up of treated and untreated patients NR: non-response (detectable HCV RNA at Week 12); RR: response-relapseSVR: sustained virologic response Vergniol J, et al. J Viral Hepat 2009;16:132–40

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