1. 4th IAS Conference , Sydney, Australia, 22-25 July 2007
Evaluation of the Agreement between Fibrotest®, Fibroscan® and APRI for the Assessment of Significant or Severe Liver Fibrosis in HIV/HCV Coinfected Patients Participating in the Prospective ANRS C013 - HEPAVIH  French Cohort Study
Y. Benhamou, M.A. Loko, M. Winnock, P. Sogni, G. Pialoux,
C. Katlama, M.A. Valantin, D. Neau, F. Dabis, D. Salmon
4th IAS Conference , Sydney, Australia, July 2007

2. BACKGROUND
Several non invasive methods have been developed as an alternative to liver biopsy for the assessment of liver fibrosis.
Among these, FibroTest®, APRI and transient elastography (FibroScan®), although not yet validated, are commonly used to assess liver fibrosis in HIV-HCV co-infected patients.
Whether these different methods agree for the diagnosis of significant or severe liver fibrosis remains unknown.

3. AIM
To assess the agreement between FibroTest ®, APRI and FibroScan ®, taken two-by-two, for the determination of significant (F ≥ 2) or severe (F ≥ 3) liver fibrosis in HIV-HCV co-infected patients.

4. METHODS
Cross sectional study (ANRS CO13 HEPAVIH prospective French Cohort )
Patients :
Positive HCV RNA
No current anti-HCV therapy
Biological samples available within 6 months of Fibroscan performance.

5. METHODS (2) Non-invasive methods :
Transient elastography (FibroScan®, FS)
- measures ‘liver stiffness’
- expressed in Kilopascals (KPa)
FibroTest® (FT)
- biochemical marker-based algorithm :
a2 macroglobulin, haptoglobin, gGT, bilirubin, apolipoprotein A1
APRI score*
based on aspartate transaminases and platelet counts :
[AST(IU/ULN) x 100 / platelets (10^9/L)]
* Wai et al. Hepatology, 2003;38:

6. METHODS (3) Thresholds for scoring liver fibrosis : Significant Severe
( F ≥ 2) (F ≥ 3)
FibroScan (KPa) > 7.1 > 9.5
FibroTest Index > > 0.58
APRI >

7. METHODS (4)
Agreement, measured by the kappa coefficient, was considered as :
poor : 0 – 0.20
fair : – 0.40
moderate : – 0.60
good : – 0.80
very good : – 1.00

8. RESULTS Characteristics of patients (N=154) * Age (yrs) 44 (26-64)
Gender (% male) 80 %
CD4 counts (/mm3) 440 ( )
Current antiretroviral treatment (%) 91.6%
HCV genotype %
2 or %
other %
* Median (range), N (%)

9. Prevalence of significant (F ≥ 2) vs minimal liver fibrosis depending on the test used
(%)
Fibrotest (FT)
Fibroscan (FS)
APRI
Here are shown the comparison for the three markersfor significant (more than F2) versus minimal fibrosis; fibrotest is in red, fibroscan in green and apri in yellow
You can see again that the fibrotest gives more severe values of fibrosis than fibroscan ; and that APRI gives the lower values of fibrosis

10. Agreement for the diagnosis of significant liver fibrosis ( F ≥ 2)
FibroScan Kappa CI
APRI
FibroTest
FibroTest Kappa CI
(N,%)
(95 %)
99 (64.3)
0.23
0.10 – 0.36
106 (68.8)
0.39
0.26 – 0.53
78 (51.3)
0.16
0.07 – 0.25

11. Prevalence of severe (F ≥ 3) liver fibrosis depending on the test used
(%)
(%)
Fibrotest (FT)
Fibroscan (FS)

12. Agreement for the diagnosis of severe liver fibrosis (F ≥ 3)
FibroScan Kappa CI
FibroTest
(95 %)
(N,%)
105 (68.2)
0.36
0.24 – 0.49

13. Disagreement between Fibrotest and Fibroscan
(> 1 point of fibrosis)
Significant fibrosis 39 patients 25.3%
Severe fibrosis 47 patients 31%
Sur 154 pts évalués discordance pour 48 pts
On a essay é de voir pourquoi pour 70% fibrotest supérieru

14. Causes of disagreement between Fibrotest and Fibroscan for severe fibrosis
47 patients
Fibrotest > FibroScan FibroScan > Fibrotest
N = 42/47 (89%) N = 5/47 (11%)
- ATAZANAVIR :  bilirubin (N=19) incomplete
- inflammatory syndrome (N=2) information (N=5)
- hemolysis (N=3)
- acute hepatitis (N=1)
- incomplete information (N=15)
Sur 154 pts évalués discordance pour 48 pts
On a essay é de voir pourquoi pour 70% fibrotest supérieru

15. Agreement for diagnosis of significant liver fibrosis (F >2)
Patients treated by Atazanavir NOT included (N=95)
FibroScan Kappa CI
APRI
FibroTest
FibroTest Kappa CI
(N,%)
(95 %)
62 (65)
0.27
0.11 – 0.43
70 (74)
0.48
0.30 – 0.65
En enlevant lers pts sous atv, la concordance des deux tests est mieux
(N,%)
(95 %)
57 (60)
0.24
0.10 – 0.37

16. Agreement for diagnosis of severe liver fibrosis (F > 3)
Patients treated by Atazanavir NOT included (N=95)
FibroScan Kappa CI
FibroTest
(N,%)
(95 %)
76 (80)
0.57
0.41 – 0.73

17. CONCLUSION (1)
In HIV-HCV co-infected patients, poor to fair agreement between APRI, FibroTest and FibroScan for grading significant or severe fibrosis.
APRI seems to underestimate significant fibrosis as compared to other tests
Between FibroTest and FibroScan, disagreement of more than one point:
25% for significant fibrosis (F > 2)
31% for severe fibrosis (F > 3)
fibrosis stage higher by FibroTest than by FibroScan in 89%

18. CONCLUSION (2)
Agreement improved when patients receiving atazanavir were not considered.
At least, in such patients, liver fibrosis is better evaluated by Fibroscan.
A limitation of our study is that these tests have not yet been compared with the gold standard assessment obtained by a liver biopsy.
Such a study is on going in order to optimize the use of non-invasive methods of fibrosis evaluation that are becoming important treatment-decision making tools.