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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 Victor de Lédinghen MD PhD CHU Bordeaux France Paris January 2012
Which method: blood sample or liver stiffness? • Hepascore • Fibrotest • Fibrometer • Liverstiffness (FibroScan)
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?
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
Liver stiffness Portal fibrosis Cholestasis Centrolobular fibrosis Stiffness Sinusoidal fibrosis Steatosis? Portal blood flow Inflammation 5
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
Combination of FibroScan and blood test: well-classified patients and theoretically avoided liver biopsies Zarski JP, et al. J Hepatol 2012; 56:55-62
Combination of tests: well-classified patients and theoretically avoided liver biopsies LB 70.8% LB 49.8% Boursier, Hy 2012
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
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
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
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
Today: useful with other parameters Clinical signs Blood sample Biomarkers Liver biopsy Stiffness Imaging(US, MRI, endoscopy)
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.
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
Question #1 • There is a cirrhosis • There is no cirrhosis • I don’t know
In 2003 • Fibroscan 25.5 kPa but IQR 29.2 kPa … • Endoscopy : no oesophageal varices • Ultrasonography : no HCC
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
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.
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
Question #2 • There is a cirrhosis • There is no cirrhosis • I don’t know
2009 • Liver biopsy : A3F4 • No varices and no HCC • 2010 • Liver stiffness 21.1 kPa (IQR 2.5) • Fibrotest 0.73
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
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.
2011 • 2 March 2011 : treatment started • Pegylated interferon • Ribavirin • Telaprevir
HCV-RNA follow-up in 2011 IU/ml PEG RIBA TELA PEG RIBA
2012 • End of treatment : end of february • HCV-RNA should be negative • New non-invasive evaluation at the end of treatment.
At the end of treatment, what do you expect? • No change of liver stiffness • Decrease of liver stiffness • Increase of liver stiffness
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