Pospective comparaison of transient elastography ... Guessab.pdf · 1st Annual Congress of the Algerian Society of Infectiology and The 5th Congress of Federation Arab Socieies of

1st Annual Congress of the Algerian Society of Infectiology and The 5th Congress of Federation Arab Socieies of Clinical

Microbiology and infectious diseases

Pospective comparaison of transient elastography,

Fibrometer,APRI and FIB-4 with liver biopsy for the assessment of fibrosis in chronic hepatitis B

N. Guessab 1, I.ouled Chikh 1, M.Merniz 2 , R. Kerbouche 1 ,0.Drir 1, N. Afredj 1,S.Ait Younes 3, N.Debzi 1 1- Hepatology, University Mustapha Hospital 2- Infectious Diseases, Boudiaf Msila Hospital

3- Pathology, University Nefissa Hamoud Parnet

Liver fibrosis

• Consequences chronic liver diseases ; CHB +++

• CHB = Dc of significant fibrosis ≥ F2 +++++++ * ≥ F2 = Initiation TRT antiviral

* F4 =Screening of HCC and varices

Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013. ozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Globaland regional mortality from 235 causes of death for 20 age groups in 199 0and 2010: A systematic analysis for the Global Burden of Disease Study2010. Lancet 2012;380:2095–2128. Fattovich G , Natural history and prognosis of hepatitis B. Semin Liver Dis. 20 Feb; 23 (1): 47- 58.

F2 F4 F3

Assessment liver fibrosis

invasive method

Liver biopsy

non-invasive methods

Biomarkers

FibroScan

OBJECTIFS Objective

study

Objective

Diagnosis accuracy FibroScan/FibroMeter /APRI/FIB-4

Liver biopsy

Comparison

patients with chronic hepatitis B

PATIENTS ET METHODES

Patients and methods

prospective study monocentric 02/01/2014 -03/15/2017

Inclusion criteria

Patients selected for liver biopsy

• Hbe Ag négative , HBV-DNA level ≥ 20.000UI /ml whatever level of ALT

• Hbe Ag positive, HBV-DNA level ≥ 20.000UI /ml, ALT > ULN

• Hbe Ag négative,HBV-DNA level 2000 -20.000UI /ml, ALT> ULN

National Consensus 2012

EASL 2012

Exclusion criteria

• Age < 16 ans

• Pregnancy

• Ascites

• Abvious Cirrhosis

• HCV, HDV or HIV coinfection

• Previous antiviral treatment

• HCC

• ALT > 5 XULN

• extra hépatic cholestasis

• Implantable cardiac devices

• Patient refuse liver biopsy

• Cardiac insufficiency

• Chronic Rénal insufficiency

Méthods I

In fasted Patients Biomarkers + FibroScan ( blood samples collected) same day Liver biopsy

Méthods II

Blood samples

• 1 heparine tube : ALT, AST, GGT, Urea , Alpha-2

macroglobuline

• 1 EDTA tube : Platelets count

• 1 citrate tube: PT

Méthods III

Wai CT, Greenson JK, Fontana RJ et al. A simple noninvasive index can predict

both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology

2003; 38:518-26.

Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et Development

of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV

coinfection. Hepatology 2006; 43:1317–1325.

APRI

FIB-4

Méthos IV

FibroMeter : FM virus 3G

• Platelets ,TP, AST, ALT ,Urea, Alpha 2 macroglobuline GGT +

Age , gender

• Résults = Excel = e-mail Echosens (Paris, France )

Méthods V

Echosens TM Paris type 502

• M or XL probes

• a single examiner

• Usual procedure

FibroScan

M XL

Méthods VI

Fibroscan Reliability Critèria: • Validated measurements ≥ 10

• Acquisition success rate > 60 % • IQR/LSM ratio < 30%

Unsuccessful results : • No valid measurement • IQR/LSM ratio >30%

Méthods VII Liver biopsy

• Percutaneous liver biopsy

• HEPAFIX® (Braun Melsungen, Germany Ø15G /1,8mm)

• Menghini technique

• specimens = formol 10 %

Méthods VIII Liver histology and staging of liver fibrosis

• paraffin embedded

• Four-micrometre-thick sections

• Staining : Hématéine Eosine Trichrome de Masson Sels d’argent

• Length LB specimen established in millimetres

• Two trained pathologists • blinded to the results of Fibroscan/ Fibromètre / APRI/FIB-4 and clinical data. • in case of discrepancies , a consensus was reached .

Méthods IX

Sttage Description

F0 no fibrosis

F1 portal fibrosis without

F2 portal fibrosis and few septa

F3 numerous septa without cirrhosis

F4 Cirrhose

Grade Description

A0

none

A1

mild

A2

moderate

A3

severe

METAVIR scoring system

Fibrosis Necrotico-inflammatoire activity

Méthods X

significant fibrosis ≥ F2 (F2, F3, F4)

Cirrhosis F4

Two clinically relevant end points

• SPSS version 21

• Continuous variables = mean ± SD or median [IQR])

• Diagnosis accuracy = Receiver-operating characteristics curves (AUROC)

*AUROC < 0.7 = Insufficient

*AUROC 0.7 -0.8 = Fair

*AUROC 0.8 -0.9 = Good

*AUROC > 0.9 = Excellent

• Optimal cut-off values = 2 different criteria (Youden test)

*Maximizing the sum of sensitivity and specificity

* Maximizing the diagnosis accuracy (% patients diagnosed correctly)

• Cut off = Sensitivity (Ss), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)

Statistical analysis


RESULTS

RESULTS I 02/01/2014 -03/15/2017

excluded patients n= 12

• inadequate LB (n =1)

•HCV Coïnfection (n =1)

•Contraindication LB (n=2)

•Refusal LB (n =1 )

• abvious Cirrhosis (n =3 )

•Previous antiviral treatment HBV (n =1)

•Inadequate FibroScan (n= 3 )

RESULTS I Characteristics of patients

• Mean Age : 37.91 [ ± 12.32], [18 – 83] years

• Sex-ratio : 1.74 Men : 63.57% (n = 89)

• Mean body mass index : 25.6 [± 4,6] Kg/m²

• Metabolic syndrome : 7.85% (n= 11)

HBV DNA

Mean

Médian

HBV DNA (UI/ml)

33 444 646,0

90 300

HBV DNA (Log)

7.5

4.95

Hbe Ag negative

RESULTS II

ALT

N

%

≤ ULN

115

82.14

> ULN

25

17.85

ULN- 2ULN

14

10.0

> 2 ULN

11

7.85

Characteristics of ALT

*

* < 5 ULN

RESULTS III Characteristics of biopsy specimens

Characteristics

Mean (sd)

Médian

Min- Max

Length (mm)

24,2 (± 9,3)

23,0

7 - 50

Number portal

space

19,8 (±8,9) 18,0 6 - 50

Number of

specimens

2,2 (±1,4) 2,0 1 - 7

Length (mm)

% (N)

≥ 20

67.86 (95)

15 - 20

17.85 (25)

<15

14.29 (20)

85.68% ≥ 15mm

65% ≥ 20mm + ≥ 11 NPS

RESULTS IV Distribution for METAVIR fibrosis stage

FIBROSIS Number %

F0 4 2.9

F1 75 53.6

F2 28 20.0

F3 26 18.5

F4 7 5.0

fibrosis stage according to

severity

N (%)

No or mild Fibrosis (F0F1)

79 (56.5)

significant fibrosis (≥ F2)

61 (43.6)

Cirrhosis (F4)

7 (5)

RESULTS V

Distribution Metavir activity grade and steatosis

Activity

Numbre

%

A0

6

4,3

A1

89

63,6

A2

39

27,8

A3

6

4,3

Stéatosis

Numbre

%

S0

70

50,0

S1

63

45,0

S2

6

4,3

S3

1

0,7

Steatosis Activity grade

RESULTS VI Characteristics Fibroscan

Probe

Success

N (%)

failure N (%)

M

128 (91.42)

12 (8.57)

XL

11 (7.85)

1 (0.7)

Reliability

Critèria

Mean

(sd)

Médian Extrêmes

Value

V M

10.93

(± 2.17)

10

10-20

Acquisition

success

rate (%)

94.86

(± .17)

100

60-100

IQR /LSM

13.65%

(± 5.91)

12%

02-29%

IQR/LSM (%)

N

%

<10

33

23,74

10 - 20

86

61,87

>20

20

14,38

85.61% IQR/LSM ≤ 20%


Receiver-operating characteristic curves

(AUROC) FibroScan,FibroMeter,APRI,FIB-4

RESULTS VI Fibroscan

Receiver-operating characteristic analysis(AUROC)

≥ F2

0.83

0.75 - 0.90

(95% CI)

F4

0.92

0.85 - 0.99

(95% CI)

Fibrosis

stage

Cut off

Se

(%)

Sp

(%)

PPV

(%)

NPV

(%)

Diagnosis

accuracy (%)

≥ F2

7.2

68,3

93,7

89,1

79,6

82,7

F4

9.6

85,7

87,9

27,2

99,1

87,8

Fibrosis

stage

Cut off Se

(%)

Sp

(%)

PPV

(%)

NPV

(%)

Diagnosis

accuracy (%)

≥ F2

7.2

68,3

93,7

89,1

79,6

82,7

F4

12.5

57,1

96,2

44,4

97,7

94,2

Maximizing the diagnosis accuracy

RESULTS VI Cut off FibroScan

Maximizing the sum of sensitivity and specificity

RESULTS VII FibroMeter

Receiver-operating characteristic analysis (AUROC)

≥ F2

F4

0.69

0.60 - 0.78

(95% CI)

0.79

0.66 - 0.92

(95% CI)

RESULTS VIII APRI


≥ F2

0.69

0.60 - 0.78

(95% CI)

F4

0.77

0.56 - 0.97

(95% CI)

RESULTS IX FIB-4

0.66

0.57 - 0.75

(95% CI)

0.89

0.80 - 0.98 (95% CI)

≥ F2 F4


DISCUSSION Discussion

Fibroscan in CHB

Results of Studies Evaluating the Performance of Transient Elastography for the Diagnosis of Liver Fibrosis

EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis: Journal of Hepatology 2015.

Study

Our study 139 0.83 0.92

Fibroscan in CHB

cut off ≥ F2


Study Diagnosis occuracy(%)

Fibroscan in CHB

cut off ≥ F2


Study Diagnosis occuracy(%)

139

Fibroscan in CHB

cut off = F4


Study Diagnosis

occuracy(%) Diagnosis

occuracy(%)

Fibroscan in CHB

cut off = F4


FibroMeter in CHB

the Performance of FM for the Diagnosis of Liver Fibrosis

-Zhou K, Gao CF, Zhao YP, Liu HL, Zheng RD, Xian JC, et al. Simpler score ofroutine laboratory tests predicts liver fibrosis in patients with chronichepatitis B. J Gastroenterol Hepatol 2010;25:1569–

1577. -Francoise Degos, Paul Perez, Bruno Roche, Amel Mahmoudi, Julien Asselineau, Hélène Voitot ,Pierre Bedossa, for the FIBROSTIC study group. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study).Journal of Hepatology 2010 vol. 53 j 1013–102 -Vincent Leroy, Nathalie Sturm, Patrice Faure, Candice Trocme, Alice Marlu, Marie-Noëlle Hilleret, Françoise Morel, Jean-Pierre Zarski. Prospective evaluation of FibroTest, FibroMeter, and HepaScore for staging liver fibrosis in chronic hepatitis B: Comparison with hepatitis C. Journal of Hepatology 2014 vol. 61 j 28–34 -Alexandra Ducancelle, MD, PhD, Vincent Leroy, MD,wz Julien Vergniol, MD,y Nathalie Sturm, MD,wz Brigitte Le Bail, MD,zJean Pierre Zarski, MD,w Eric Nguyen Khac, MD, PhD,Dominique Salmon,MD,Victor de Ledinghen, MD,and Paul Cale`s. A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases. J Clin Gastroenterol Volume 00, Number 2017

Study

Our study 0.69 0.77

APRI in CHB The Performance of APRI for the Diagnosis of Liver Fibrosis

meta-analysis HBV Xiao G et al. Hepatology 2015;292-302

Our study 0.69 0.79

FIB-4 in CHB the Performance of FIB-4 for the Diagnosis of Liver Fibrosis

Meta analyse HBV Xiao G et al. Hépatologie 2015; 292-302

DISCUSSION Conclusion

0ur study shows

• FibroScan is an accurate method for the diagnosis of fibrosis stage in patients with chronic hepatitis B

• On the contrary, FibroMeter, APRI and FIB-4 are not a good tool for predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis.

Pospective comparaison of transient elastography ... Guessab.pdf · 1st Annual Congress of the Algerian Society of Infectiology and The 5th Congress of Federation Arab Socieies of

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