Introduction
Methods
Design of Meta-Analysis of Published Studies
Search Strategy
Inclusion and Exclusion Criteria
Statistical Methods Used in AUROCs Meta-Analysis
Design of Individual Data Meta-Analysis
Patients
Biochemical Analysis
Liver Biopsies
Statistical Analysis of Integrated Database
Obuchowski Measure
Main Endpoint
Sensitivity Analyses
Results
Databases
Study | Number of patients | Methodology cause if mixed (n) | Age (y) | Stage/prevalence | AUROC SE | F0 (%) | F1 (%) | F2 (%) | F3 (%) | F4 (%) | DANA | Size (mm) | Independent | Biopsy FT/median days |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
FibroTest | ||||||||||||||
Myers et al. [10] | 209 | Prospective (42), Retrospective (167) | 39 | F2F3F4 0.29 | 0.78 | 76 (36) | 72 (34) | 32 (15) | 10 (5) | 19 (9) | 2.31 | 18 | No | 1 |
0.04 | ||||||||||||||
F4 0.09 | 0.87 | |||||||||||||
0.04 | ||||||||||||||
Poynard et al. [11] | 214 | Prospective | 40 | F2F3F4 0.67 | 0.77 | 14 (8) | 53 (25) | 119 (24) | 55 (26) | 40 (19) | 2.17 | ? | Mixed | 150 |
0.03 | ||||||||||||||
F4 0.19 | ||||||||||||||
Sebastiani et al. [12] | 110 | Prospective | 43 | F2F3F4 0.69 | 0.85 | (14) | (18) | (36) | (12) | (20) | 2.19 | 17 | Yes | 0 |
0.04 | ||||||||||||||
F4 | ||||||||||||||
Zhao et al. [13] | 123 | Prospective | ? | F2F3F4 | 0.81 | 25 (20) | 27 (22) | 31 (25) | 29 (24) | 11 (9) | 2.20 | ? | Yes | ? |
0.04 | ||||||||||||||
F4 | 0.72 | |||||||||||||
0.07 | ||||||||||||||
Poynard et al. [14•] | 924 | Retrospective | 39 | F2F3F4 0.33 | 0.76 | 21 (2) | 596 (65) | 160 (17) | 69 (7) | 78 (8) | 1.77 | 13 | Mixed | 90 |
0.02 | ||||||||||||||
F4 0.08 | 0.83 | |||||||||||||
0.02 | ||||||||||||||
Gui et al. [30] | 100 | Prospective | ? | F2F3F4 | 0.84 | ? | ? | ? | ? | ? | ? | ? | Yes | 0 |
0.05 | ||||||||||||||
F4 | 0.86 | |||||||||||||
0.07 | ||||||||||||||
Bottero et al. [31] | 108 | Prospective, HIV coinfected | 42 | F2F3F4 0.57 | 0.77 | 11 (9) | 36 (33) | 28 (26) | 17 (16) | 16 (15) | 2.04 | 17 | Yes | 30 |
0.04 | ||||||||||||||
F4 0.15 | 0.87 | |||||||||||||
0.09 | ||||||||||||||
Bonnard et al. [32] | 54 | Prospective | 35 | F2F3F4 0.70 | 0.79 | 5 (8) | 13 (22) | 19 (32) | 8 (14) | 14 (24) | 2.26 | 21 | Mixed | 120 |
0.06 | ||||||||||||||
F4 0.24 | 0.85 | |||||||||||||
0.05 | ||||||||||||||
FibroTest integrated databasea
| 1303 | Retrospective and prospective (1303) | 39 | F2F3F4 0.38 | 0.76 | 108 (8) | 707 (54) | 227 (17) | 133 (10) | 128 (10) | 1.94 | 15b
| Mixed | 90 |
0.03 | ||||||||||||||
F4 0.10 | 0.79 | |||||||||||||
0.02 | ||||||||||||||
Hepascore | ||||||||||||||
Bottero et al. [31] | 108 | Prospective, HIV coinfected | 42 | F2F3F4 0.57 | 0.74 | 11 (10) | 36 (33) | 28 (26) | 17 (16) | 16 (15) | 2.04 | 17 | Yes | 30 |
0.04 | ||||||||||||||
F4 0.15 | 0.91 | |||||||||||||
0.09 | ||||||||||||||
Zhou et al. [38] | 146 | Prospective | 33 | F2F3F4 | 0.77 | 15 | 63 | 26 | 27 | 15 | 2.26 | >15 | Yes | 7 |
0.47 | 0.06 | (10) | (43) | (18) | (18) | (10) | ||||||||
F4 0.10 | 0.78 | |||||||||||||
0.05 | ||||||||||||||
Elastography | ||||||||||||||
Fraquelli et al. [37] | 104 | Prospective | 45 | F2F3F4 0.52 | ? | ? | ? | 21 (20) | 17 (16) | 16 (16) | ? | 30 | Yes | Same session |
F4 0.16 | ? | |||||||||||||
Miailhes et al. [36] | 59 | Prospective | 43 | F2F3F4 | 0.85 | 4 (7) | 19 (32) | 16 (27) | 8 (14) | 12 (20) | 2.06 | 16 | Yes | 3 |
0.05 | ||||||||||||||
F4 | 0.96 | |||||||||||||
0.02 | ||||||||||||||
Marcellin et al. [33] | 173 | Prospective | 40 | F2F3F4 0.50 | 0.82 | 16 (9) | 70 (41) | 44 (25) | 29 (17) | 14 (8) | 1.84 | 16 | Yes | 2 |
0.04 | ||||||||||||||
F4 0.08 | 0.93 | |||||||||||||
0.08 | ||||||||||||||
Wang et al. [35] | 88 | Prospective | ? | F2F3F4 ? | 0.86 | ? | ? | ? | ? | ? | ? | 15 | Yes | ? |
0.05 | ||||||||||||||
F4 ? | 0.89 | |||||||||||||
0.04 | ||||||||||||||
Sporea et al. [34] | 140 | Retrospective | 39 | F2F3F4 0.77 | 0.66 | 1 (0.7) | 32 (23) | 67 (48) | 33 (24) | 7 (5) | 1.47 | >20 | Yes | Same session |
0.05 | ||||||||||||||
F4 0.05 | 0.97 | |||||||||||||
0.08 | ||||||||||||||
Bonnard et al. [32] | 54 | Prospective | 35 | F2F3F4 0.70 | 0.87 | 5 (8) | 13 (22) | 19 (32) | 8 (14) | 14 (24) | 2.26 | 21 | Mixed | 120 |
0.04 | ||||||||||||||
F4 0.24 | 0.88 | |||||||||||||
0.03 |
Comparison Between Biomarker Performances According to Published Studies
Diagnosis of Advanced Fibrosis
Diagnosis of Cirrhosis
Sensitivity Analysis
FibroTest’s Performance According to Individual Data Meta-Analysis (Table 2)
Performance Between All Fibrosis Stages
Advanced fibrosis | Pairwise comparisons between all stages, Obuchowski measure | ||
---|---|---|---|
Characteristic (no. of patients) | Not standardized AUROC | Significance (P) | AUROC (95% CI) |
All (1303) | 0.76 (0.73–0.79) | 0.844 (0.832–0.856) | |
Gender | >0.10 | ||
Male (941) | 0.75 (0.72–0.78) | ||
Female (362) | 0.76 (0.70–0.81) | ||
Length of biopsy | >0.10 | ||
<25 mm (942) | 0.76 (0.71–0.85) | ||
≥25 mm (148) | 0.79 (0.71–0.85) | ||
Not available (213) | 0.76 (0.69–0.82) | ||
Ethnicitya
| 0.06 | P > 0.10 | |
Asian (546) | 0.72 (0.67–0.76) | 0.836 (0.814–0.848) | |
Caucasian (601) | 0.78 (0.74–0.82) | 0.853 (0.839–0.867) | |
Sub-Saharan (156)b
| 0.80 (0.72–0.86) | ||
HBeAgc,d
| 0.046 | P > 0.10 | |
Absent (548) | 0.73 (0.68–0.77)e
| 0.854 (0.838–0.870) | |
Present (753) | 0.78 (0.75–0.82) | 0.831 (0.814–0.848) | |
After treatment | >0.10 | ||
No (723) | 0.75 (0.71–0.78) | ||
Yes (392) | 0.78 (0.72–0.82) | ||
Not available (188) | 0.78 (0.70–0.85) | ||
HBV genotype | >0.10 | ||
Genotype A (61) | 0.77 (0.57–0.88) | ||
Genotype non-A (137) | 0.77 (0.73–0.79) | ||
Not available (1105) | 0.76 (0.73–0.79) | ||
Viral load (IU/mL) | >0.10 | ||
<3 Log (276) | 0.79 (0.73–0.84) | ||
3–5 Log (115) | 0.82 (0.72–0.88) | ||
5–7 Log (330) | 0.72 (0.66–0.77) | ||
>7 Log (464) | 0.77 (0.72–0.81) | ||
Not available (118) | 0.76 (0.65–0.83) | ||
ALT <50 IU/L | >0.10 | ||
No (825) | 0.75 (0.72–0.79) | ||
Yes (478) | 0.76 (0.70–0.80) | ||
ALT <25 IU/L | >0.10 | ||
No (1151) | 0.76 (0.73–0.79) | ||
Yes (152) | 0.72 (0.57–0.82) |