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Independent Assessment of Non-invasive Liver Fibrosis Biomarkers in HIV/HCV-co-infected Patients: The Fibrovic Study-ANRS HC 02 RIBAVIC
Patrice Cacoub*1, F Carrat2, P Bedossa3, J Lambert2, G Penaranda4, C Perronne5, S Pol6, P Halfon7, and ANRS HC 02 RIBAVIC
1Hosp Pitie-Salpetriere, Paris, France; 2Univ Paris 6, GHU-Est, France; 3Hosp Beaujon, Clichy, France; 4CDL Pharma, Marseille, France; 5Hosp Raymond Poincare, Garches, France; 6Hosp Necker, Paris, France; and 7Lab Alphabio, Marseille, France
Background:
Many non-invasive liver fibrosis scores have been proposed as
alternatives to liver biopsy in hepatitis C virus (HCV) -infected patients, ie,
Fibrotest, APRI, Forns, Hepascore, and Fibrometer. Fibrotest, SHASTA, and Fib-4
scores have been tested in small cohorts of HIV/HCV-co-infected patients. Our
aim was to compare diagnostic accuracies of Fibrotest, APRI, Forns, Hepascore,
Fibrometer, SHASTA, and Fib-4 scores in a large cohort of HIV/HCV-co-infected
patients.
Methods: Before inclusion in the prospective ANRS HC02
Ribavic trial, 274 HIV/HCV-co-infected patients, naïve of HCV treatment, had
had a liver biopsy: 198 (72%) were men;
aged 39.9 years; liver biopsy 18.5 mm; fibrosis stage (METAVIR) F2 in 110
(41%), F3 in 67(23%), and F4 in 29(11%). Diagnostic accuracy of each score was
determined by area under the ROC curve (AUROC), and the accuracy (rate of
well-classified patient) compared to liver biopsy. AUROC were compared with
Hanley-McNeil test, and accuracies with McNemar or χ2 test.
Note that low values of AUROC were expected, since our sample did not include
patients with F0.
Results: Fibrotest, Hepascore, and Fibrometer were
more accurate than other scores: AUROC 0.64 (95%CI 0.58 to 0.70), 0.69
(0.63 to 0.74), and 0.70 (0.61 to 0.73) for the diagnosis of
significant fibrosis (≥F2), respectively. Values for the diagnosis of ≥F3
were 0.72 (0.66 to 0.77), 0.76 (0.71 to 0.81), and 0.78 (0.73 to
0.83), respectively. For the diagnosis of cirrhosis, AUROC were 0.81
(0.76 to 0.85), 0.83 (0.78 to 0.88), and 0.84 (0.78 to 0.88).
Comparison of these 3 tests (see the table) showed that for global analysis,
accuracy Fibrometer > Fibrotest, but not different from Hepascore. In a stage-by-stage fibrosis analysis, accuracy Fibrometer >
Hepascore > Fibrotest except for F1 where Fibrotest > Fibrometer.
Search for a better test by using combination of Fibrotest, Hepascore, and Fibrometer
did not increase significantly the diagnostic performances.
Conclusions: In HIV/HCV-co-infected patients, use of
non-invasive liver fibrosis biomarkers can correctly classify only patients
with severe fibrosis (≥F3, accuracies 74 to
97%). For global analysis, accuracy of Fibrometer >
Fibrotest, but similar to Hepascore. In a stage-by-stage fibrosis
analysis, Fibrometer is better for the diagnosis of ≥F2 and ≥F3
stages whereas Fibrotest is better for the diagnosis of F1.
|
|
Accuracy (%)
|
|
METAVIR
|
Global Analysis
|
F1
|
F2
|
≥F2
|
F3
|
≥F3
|
|
# patients
|
274
|
68
|
110
|
206
|
67
|
96
|
|
Fibrotest *
|
61
|
60
|
51
|
62
|
67
|
74
|
|
Hepascore *
|
68
|
47
|
61
|
75
|
88
|
81
|
|
Fibrometer *
|
71
|
37
|
70
|
82
|
97
|
97
|
|
Fibrotest vs Hepascore **
|
0.13
|
0.04
|
0.03
|
<0.01
|
<0.01
|
<0.01
|
|
Fibrotest vs Fibrometer **
|
0.02
|
<0.01
|
<0.01
|
<0.01
|
<0.01
|
<0.01
|
|
Hepascore vs Fibrometer **
|
0.52
|
0.09
|
0.09
|
0.01
|
0.03
|
0.03
|
* cut-off =
0.5; ** p
|