Presentation is loading. Please wait.

Presentation is loading. Please wait.

Michel BEAUGRAND. EVALUATION OF LIVER FIBROSIS BLOOD TESTS, LIVER BIOPSY AND FIBROSCAN M. Beaugrand Service d’Hépatologie Hopital J. Verdier BONDY 93143.

Similar presentations


Presentation on theme: "Michel BEAUGRAND. EVALUATION OF LIVER FIBROSIS BLOOD TESTS, LIVER BIOPSY AND FIBROSCAN M. Beaugrand Service d’Hépatologie Hopital J. Verdier BONDY 93143."— Presentation transcript:

1 Michel BEAUGRAND

2 EVALUATION OF LIVER FIBROSIS BLOOD TESTS, LIVER BIOPSY AND FIBROSCAN M. Beaugrand Service d’Hépatologie Hopital J. Verdier BONDY et Université Paris XIII PHC JANUARY 07

3 EVALUATION OF FIBROSIS : WHY ? Causal agent Causal agent Chronic liver DiseaseCirrhosis Decompensation Hepatocellular Decompensation Hepatocellular 2 % to 5 % per year carcinoma 2 % to 5 % per year carcinoma 2 % to 5 % per year Death 4 % per year Fibrosis Distorted architecture Portal hypertension Liver failure Carcinogenesis FIBROSIS

4 ASSESSMENT OF FIBROSIS : WHY ? Management of individual patients Significant fibrosisTreatment Significant fibrosisTreatment CirrhosisScreening for varices and HCC CirrhosisScreening for varices and HCC Evaluation of treatments Antiviral and antifibrotic drugs Antiviral and antifibrotic drugs Screening for cirrhosis or extensive fibrosis In high risk patients In high risk patients

5 EVALUATION OF FIBROSIS : HOW ? - Liver biopsy - Blood tests Genuine serum markers of fibrosis :Genuine serum markers of fibrosis : by products of extracellular matrix metabolism. Probabilistic indexes = surrogate markers.Probabilistic indexes = surrogate markers. - Fibroscan ( transcient elastography)

6 LIVER BIOPSY : LIMITATIONS Acceptability Acceptability - patients are often reluctant - even some doctors are reluctant Cost Cost Morbidity Morbidity Reliability Reliability - liver sample size ideally ≥ 25 mm - pathologist’s experience - suboptimal reproductibility of scoring systems - quantitative assessment unpractical

7 LENGH OF LIVER BIOPSY Biopsy length Bedossa et al, Hepatology 2003

8 LIVER BIOPSY : PROS AND CONS PRO. Not influenced by extrahepatic conditions. Allows analysis of elementary lesions and comobidities. May allow assessment of fibrogenesis (molecular biology) CON. Sampling error. Dependant of pathologist’s experience. Unavalaible in large parts of the world

9 BLOOD TESTS Matrix related PIIINP, collagen type IV, laminin Hyaluronic acid, MMP, TIMP Non maxtrix related AST, ALT, gamma GT Bilirubin, prothrombine, platelets Gammaglobulins, ferritin Alpha 2 macroglobulin, haptoglobin Apo A1, cholesterol, HOMA

10 Poynard, 1991Prothrombine, GGT, Apo A1PGA Bonacini, 1997AST/ALAT, platelets, prothrombine Imbert-Bismut, 2001bili, GGT, hapto., a2MG, apoA1Fibrotest Luo, 2002glob/alb, platelets, AST/ALT Forns, 2002age, GGT, cholesterol, platelets Kaul, 2002sex, ang.spider angiomas, AST, platelets Wai, 2003AST/plateletsAPRI Sud, 2004age, AST, cholesterol, HOMA, alcohol Lainé, 2004hyaluronate, transferin Rosenberg, 2004age, hyalur., col IV, col VI, laminin, PIIINP, TIMP-1 ELF Patel, 2004TIMP-1, a2MG, hyaluronateFibrospect Leroy, 2004PIIIMP, MMP1 Hui, 2005BMI, platelets, albumin, bilirubin Lok, 2005AST/ALT, platelets, INR Adams, 2005bili, GGT, hyaluronate, a2MG, age, sexHepascore Cales, 2005AST, platelets, prothrombine, hyaluronate, Fibrometre urea, age urea, age BLOOD TESTS

11 Imbert-Bismut et al. Lancet 2001;357: Fibrotest ® BLOOD TESTS Metavirindex VHC (n= 339)

12 Imbert-Bismut et al. Lancet 2001;357: Fibrotest ® BLOOD TESTS HCV (n=339) Métavir ≥ F2 AUC = 0,827 Index < 0,10 NPV 100% Index > 0,60 PPV > 90% Liver Biopsy: - 46%

13 BLOOD TESTS Ref.TestAUCConstructionValidation Imbert-Bismut, 2001 Fibrotest Forns, Wai, 2003 APRI Patel, 2004 Fibrospect0.83 Rosenberg, 2004 ELF0.78 Leroy, Sud, Adams, 2005 Hepascore F0-1 vs F2-3-4 HCV : F0-1 vs F2-3-4

14 BLOOD TESTS Ref.TestAUCConstructionValidation Kaul, Wai, 2003 APRI Rosenberg, 2004 ELF0.89 Le Calvez, 2004 Fibrotest0.92 Adams, 2005 Hepascore Lok, F vs F4 (cirrhosis) HCV : F vs F4 (cirrhosis)

15 PRO. Easy, non invasive,not too costy. Allow to split patients in 3 groups - those without significant fibrosis - those with extensive fibrosis or cirrhosis - intermediate CON. Studied mainly in naive patients with HCV chronic hepatitis. External validation lacking (except fibrotest). Require standardisation of biochemical methods. Poorer performances in HBV patients or coinfected HCV-HIV. Possible influence of extrahepatic conditions. No international consensus BLOOD TESTS : PROS AND CONS

16 2.5 cm 4 cm 1 cm  Volume ELASTOMETRY (FIBROSCAN) Probe Sandrin et al. Ultrasound Med Biol 2003;29:1-8 LB x 100

17 HOW TO MEASURE ELASTICITY ? To generate an elastic Shear vawe Shear vawe To measure its spead Vs Elasticity Elasticity E V S 2 E  V S 2

18 2.5 cm 4 cm 1 cm  Volume of exploration Volume of exploration > 3 cm 3 Probe position Probe

19 PATIENTS WITH HCV CHRONIC HEPATITIS 327 HCV + patients with noascites 251 patients included 53 patients excluded biopsy not suitable for fibrosis stage assessment: less than 10 portal tracts in the absence of cirrhosis 23 patients excluded: unreliable stiffness measurement: success rate less than 60% upon 10 measurements Small biopsy 126 patients Large biopsy 125 patients

20 BOX PLOTS. N= Fibrosis stage (METAVIR) median IQR maximum minimum Legend Stiffness (kPa) (logarithmic scale)

21 AUROC ( CONFIDENCE INTERVALS 95%) - F≥2 : 0.79 ( ) - F≥3 : 0.91 ( ) - F=4 : 0.97 ( ) F≥2 F≥3 F=4 ROC CURVES

22 UNI AND MULTIVARIATE ANALYSIS  Univariate analysis (Kendall’s coefficient) Fibrosis Activity Steatosis Fibrosis Activity Steatosis Stiffnessr p< Fibrosisr p-<  Multivariate analysis (multiple regression) Only fibrosis was significantly correlated to liver stiffness measurement.

23 VALIDATION OF DIAGNOSIS ACCURACY IN AN INDEPENDENT HCV POPULATION Total number of included patients: 639 Number of unreliable liver samples: 86 (13%) Number of unreliable LSM: 59 (9%) Patients kept for statistical analysis : 494METAVIRF01234% A0123 % SteatosisS % Univariate Spearman correlation METAVIR F: 0.70 (p << 0.001) METAVIR A: 0.45 (p << 0.001) Steatosis: 0.35 (p << 0.001) Area under ROC curves (95% confidence interval) F01 versus F234 = 0.84 ( ) F012 versus F34 = 0.93 ( ) F0123 versus F4 = 0.96 ( )

24 - Results Patients Causes : 71 VHC 14 VHB 15 VHC+HIV 2 VHB+HIV 1 VHC+VHB  F2  F3= F4 AUROC LIVER BIOPSIES > 30 mm F0F1F2F3F4 N Fibrosis Score :

25 CUT-OFF VALUES * ThresholdSensitivitySpecificityLR (kPa) F  F  F = * Obtained by the jack-knife method. The optimum thresholds were chosen to maximize the sum of sensitivity and specificity.

26 FIBROSIS AREA (morphometry) 69 patients with chronic hepatitis C without ascites, and previous anti-viral treatment - Patients F1F2F3F Results Parametersr Fibrosis area METAVIR score 0.66 Elasticity METAVIR score0.65 Elasticity fibrosis area0.74 Spearman correlation test p <  Liver elasticity is closely correlated to fibrosis area. METAVIR

27 FIBROSCAN VERSUS BLOOD TESTS Elasticité (kPa) FibroScanFibroTest APRI Score METAVIR de fibrose Castera Al. Gastroenterology 2005

28 CONCORDANCE WITH LIVER BIOPSY F01/F234F012/F34F0123/F4 APRI FibroTest FibroScan Combinaison FibroTest+FibroScan AUROC Percentage of concording results F01/F234F0123/F4 FibroTest8081 FibroScan7383 Combinaison8495 FibroTest+FibroScan

29 PROPOSED COMBINATION OF NON INVASIVE METHODS FibroScan + FibroTest Concordance Discordance Fibrose minime (FS < 7.1 kPa + FT < F2) Fibrose modérée (FS  7.1 kPa + FT  F2) Fibrose sévère (FS  9.5 kPa + FT  F3) Biopsy Follow-upTreatment Treatment HCC screening Follow-up treatment Castera et Al. Gastroenterlogy 2005

30 FIBROSCAN IN HBV PATIENTS 202 patients - 15 non interpretable biopsies - 14 LSM considered as non reliable Statistical analysis on 173 patients AUROC F01 versus F234: 0.81 ( ) F012 versus F34: 0.93 ( ) F0.123 versus F4: 0.93 ( )

31 FIBROSCAN PROS AND CONS  PRO -easy, quick, not too costy - very specific for extensive fibrosis or cirrhosis - Allows to split patients between 3 groups. Without significant fibrosis. With extensive fibrosis or cirrhosis. Intermediate - closely related to the area of fibrosis in patients with chronic hepatitis  CON - high rate of failure in obese patients - doesn’t take in account liver architecture - disturbed in acute conditions

32 SCREENING IN HIGH RISK PATIENTS LSM Blood tests Confirmation of cirrhosis LB LSM>13 kPa oui Absence of cirrhosis Suspected cirrhosis non 227 patients in alcoholic abstinence program

33 BEFORE TREATMENT END OF TREATMENT 6 MONTHS AFTER All (n=85) 14.1 ± ± ± 8.6 SVR 12.0 ± ± ± 2.4 RR 14.6 ± ± ± 7.2 NR 16.9 ± ± ± 12.2 FOLLOW-UP OF LSM IN TREATED PATIENTS WITH CHRONIC HEPATITIS C

34 CONCLUSION 1) Liver biopsy has been partly challenged by non invasive methods for assessment of liver fibrosis 2) Non invasive methods have their own limitations : 2 might be better than one 3) Fibroscan could become a useful tool for assessing fibrosis variations


Download ppt "Michel BEAUGRAND. EVALUATION OF LIVER FIBROSIS BLOOD TESTS, LIVER BIOPSY AND FIBROSCAN M. Beaugrand Service d’Hépatologie Hopital J. Verdier BONDY 93143."

Similar presentations


Ads by Google