Non-invasive assessment of liver fibrosis

Transcription

1 Non-invasive assessment of liver fibrosis Victor de Lédinghen MD PhD Bordeaux France Madrid 30 May 2012

2 Summary Why? How? When?

3 Why? Treatment Severity of cirrhosis Prognosis Hepatocellular carcinoma Normal liver Cirrhosis Transplantation

4 How? Blood sample? Liver stiffness? FibroScan ARFI

5 Blood tests in HIV patients APRI FIB-4 Forns score Free AST ALT platelets.. Fibrotest Fibrometer Expensive α2 macroglobulin, GGT, bilirubin

6 False positive or negative Utilize non specific serum biochemical markers Alpha-2 macroglobulin Haptoglobin Gamma-glutamyl transpeptidase Total bilirubin Apolipoprotein A1 Drugs? Hemolysis? Gilbert s syndrome?

7 Liver stiffness in HIV patients Portal fibrosis Cholestasis Centrolobular fibrosis Sinusoidal fibrosis Stiffness Portal blood flow Steatosis? Inflammation 7

8 Liver stiffness measurement 10 measurements IQR < 30%

9 Take home message # 1 Before making any conclusions, careful examination of the following is required: All parameters of blood tests Reliable measurement of liver stiffness In case of unreliable or doubtful results another method should be used A liver biopsy should be discussed

10 When? Indication of treatment Significant fibrosis? Cirrhosis? Follow-up after treatment Severity of cirrhosis Prognosis

11 Free or expensive blood tests? demonstrated high accuracy and accurately predicted significant fibrosis and cirrhosis

12 FIB-4 in HIV-HCV patients Not enough! Shire NJ et al. Clin Gastroenterol Hepatol 2009;7: N=173

13 APRI FIB-4 FORNS in HIV-HCV patients Not enough! Tural C et al, Clin Gastroenterol Hepatol 2009;7: N=324

14 Fibrotest in HIV-HCV patients Not enough! Sebastiani G et al. J Viral Hepat 2011;34: N=158

15 Blood tests in HIV-HCV patients Significant fibrosis AUROCS Calès P et al. J Hepatol 2010;53: Cacoub P et al. J Hepatol 2008;48:765-73

16 Blood tests in HIV-HBV patients 1 0,95 FibroMeter 1G Fibrotest Hepascore Adjusted AUROC 0,9 0,85 0,8 0,75 0,7 0,65 0,6 Significant fibrosis Severe fibrosis Cirrhosis Bottero J et al. J Hepatol 2009; 50: N= cirrhosis

17 Take home message # 2 Current non-invasive blood tests of fibrosis assessment have poor discriminatory capacity in HIV-HCV patients. Fibrometer needs further evaluation.

18 Liver stiffness in HIV-HCV patients FibroScan N AUC F234 AUC F4 de Lédinghen 0,97 Vergara 0,89 0,93 0,96 Macias 0,86 de Lédinghen V et al. JAIDS 2006;41:175-8 Vergara S et al. CID 2007;45: Macias J et al. J Hepatol 2008;49:916-22

19 Liver stiffness in HIV-HCV patients ARFI Not enough! Sebastiani G et al. J Viral Hepat 2011;34: N=158

20 Liver stiffness (FibroScan) in HIV- HBV patients N=57 Miailhes P et al. J Viral Hepat 2011;18:61-69

21 Take home message # 3 For the diagnosis of cirrhosis, liver stiffness measurement using FibroScan is the best method For the diagnosis of significant fibrosis, there is no good method. Maybe a combination of liver stiffness measurement + blood test could be useful.

22 When? Indication of treatment Follow-up after treatment Severity of cirrhosis Prognosis

23 Liver stiffness after treatment Time (months) Barreiro P et al. AVT 2007

24 Liver stiffness measurement: a predictive factor of response to treatment? Prometheus Index AUROC : Medrano J et al. CID 2010;51:

25 Take home message # 4 During the follow-up of treated patients with sustained virological response, there is a decrease of biochemical tests or liver stiffness. However, we need further studies for the interpretation of this decrease Is it a regression of liver fibrosis? Is it a regression of inflammation?

26 When? Indication of treatment Follow-up after treatment Severity of cirrhosis Prognosis

27 Liver stiffness and Hepatic Vein Pressure Gradient HIV-HCV patients N=38 Sanchez-Conde M et al. J Viral Hepat 2011;18:685-91

28 Diagnosis of oesophageal varices stage 2 or 3 AUROCS Castéral L et al. J Hepatol 2012;56:

29 Liver stiffness and severity of cirrhosis kpa Liver stiffness No EV stage 2/3 No Child-Pugh B or C No past history of ascites No hepatocellular carcinoma No variceal bleeding EV: esophageal varices Foucher J, et al. Gut 2006;55:403 8

30 Liver stiffness and hepatocellular carcinoma 866 patients with HCV infection, 3-year follow up Hepatocellular carcinoma during follow-up: 77 Cumulative Incidence P < LSM > 25 kpa 20 < LSM < 25 kpa 15 < LSM < 20 kpa 10 < LSM < 15 kpa LSM < 10 kpa No. At risk < 10 kpa kpa kpa kpa > 25 kpa Years After Enrollment Masuzaki R et al, Hepatology 2009;49:

31 Natural history of fibrosis and cirrhosis Garcia-Tsao G et al. Hepatology 2010;51:1-5

32 Natural history of fibrosis and cirrhosis Liver stiffness kpa Garcia-Tsao G et al. Hepatology 2010;51:1-5 Foucher J, et al. Gut 2006;55:403 8

33 Take home message # 5 Non-invasive methods are insufficient to confidently predict the presence of oesophageal varices in clinical practice Liver stiffness is associated with the severity of cirrhosis and offers a mean for rapid discrimination of different steps of progression within the stage of compensated cirrhosis.

34 When? Indication of treatment Follow-up after treatmenr Severity of cirrhosis Prognosis

35 Fibrotest and survival HCV patients Overall survival AUROC 0.76 ( ) Ngo S et al, Clin Chemistry 2006;52: N=537 Median follow-up: 5 years

36 Liver stiffness and survival HCV patients 1457 HCV patients; follow-up 5 years Overall survival: 91.7% Fibrotest FibroScan Overall survival (%) P < < 0.75 > 0.75 > 0.80 > 0.85 > 0.90 > 0.95 Overall survival (%) 1.0 0,8 0,6 0,4 0,2 P < < 9.5 kpa > 9.5 kpa > 30 kpa > 20 kpa > 40 kpa > 50 kpa , Follow-up (months) Follow-up (months) Vergniol J, et al. Gastroenterology 2011;140:1970 9

37 APRI and liver related mortality HIV-HCV patients <1.5 >1.5 N=303 (207 HIVHCV) Nunes D et al. Am J Gastroenterol 2010;105: Follow-up: 3 years

38 Survival of HIV patients with cirrhosis according to liver stiffness 194 HIV infected patients (+ HBV or HCV) All with FS > 14.5 kpa at inclusion Death: 5.8 yearly Predictive factors of mortality: MELD > 11 LSM > 28.7 kpa Tuma P et al. AIDS 2010, 24:

39 Take home message # 6 Fibrotest and liver stiffness measurement are strong predictors of survival in HCV and co-infected patients

40 CONCLUSION In clinical practice Before making any conclusions, careful examination of the following is required: All parameters of blood tests Reliable measurement of liver stiffness Current non-invasive blood tests of fibrosis assessment have poor discriminatory capacity in HIV-HCV patients. For the diagnosis of cirrhosis and its severity, liver stiffness measurement using FibroScan is the best method.

41 For the assessment of the severity of chronic liver diseases, we have Clinical signs Blood sample Biomarkers Liver biopsy Stiffness Imaging (US, MRI, endoscopy)