Table 8.
The diagnostic performance of serum markers for liver fibrosis in patients with CHC
| Serum marker | Reference | No. of patients | Nation | Significant fibrosis (≥F2) |
Advanced fibrosis (≥F3) |
Cirrhosis (F4) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of patients (%) | AUC (95% CI) | Cutoff value | Sensitivity%/specificity% | No. of patients (%) | AUC (95% CI) | Cutoff value | Sensitivity%/specificity% | No. of patients (%) | AUC (95% CI) | Cutoff value | Sensitivity%/specificity% | ||||
| FIB-4 | Vallet-Pichard et al. [157] (2007) | 847 | France | - | - | - | - | 146 (17.2) | 0.85 (0.82–0.89) | <1.45 | 74.0/80.0 | 61 (7.2) | 0.91 (0.86–0.95) | - | - |
| >3.25 | 37.0/98.0 | ||||||||||||||
| Martinez et al. [158] (2011) | 340 | Spain | 229 (67.3) | 0.85 (0.81–0.89) | - | - | 155 (45.5) | 0.87 (0.83–0.91) | <1.45 | 92.0/64.0 | 124 (36.4) | 0.89 (0.85–0.92) | - | - | |
| <3.25 | 54.0/91.0 | ||||||||||||||
| Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.76 (0.71–0.80) | - | - | 132 (30.3) | - | - | - | 61 (14.0) | 0.83 (0.76–0.89) | - | - | |
| Li et al. [160] (2014) | 1,529 | US | - | - | - | - | 610 (39.9) | 0.83 (0.81–0.85) | - | - | 348 (23.0) | 0.87 (0.85–0.88) | - | - | |
| Yen et al. [161] (2018) | 1,716 | Taiwan | 908 (52.9) | 0.70 (0.68–0.72) | 2.9 | 62.7/78.0 | 745 (43.4) | 0.73 (0.71–0.75) | 2.9 | 69.1/76.1 | 436 (25.4) | 0.73 (0.70–0.75) | 3.1 | 72.0/73.4 | |
| Mada et al. [162] (2020) | 496 | US | 312 (62.9) | 0.80 (0.74–0.86) | - | - | 168 (33.9) | 0.88 (0.84–0.93) | ≤1.45 | 82.0/58.0 | 74 (14.9) | 0.93 (0.89–0.97) | - | - | |
| ≥3.25 | 39.0/92.0 | ||||||||||||||
| APRI | Wai et al. [9] (2003) | 270 | US | 91 (47.0) | 0.80 (0.74–0.87) | ≤0.5 | 91.0/47.0 | - | - | - | - | 28 (15.0) | 0.89 (0.84–0.94) | ≤1.0 | 89.0/75.0 |
| ≤1.5 | 41.0/95.0 | ≤2.0 | 57.0/93.0 | ||||||||||||
| Paggi et al. [163] (2008) | 430 | Italy | - | - | - | - | 160 (37.0) | - | ≤1 | 70.0/79.0 | 85 (20.0) | - | >2 | 36.0/92.0 | |
| Martinez et al. [158] (2010) | 340 | Spain | 229 (67.3) | 0.83 (0.79–0.88) | ≤0.5 | 91.0/51.0 | 155 (45.5) | 0.86 (0.82–0.90) | - | - | 124 (36.4) | 0.86 (0.82–0.90) | ≤1 | 82.0/74.0 | |
| ≤1.5 | 47.0/93.0 | ≤2 | 49.0/91.0 | ||||||||||||
| Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.76 (0.72–0.81) | 0.5 | 33.1/96.6 | - | - | - | - | 61 (14.0) | 0.86 (0.81–0.91) | 2.0 | 7.1/99.7 | |
| Li et al. [160] (2014) | 1,529 | US | - | - | - | - | 610 (39.9) | 0.81 (0.78–0.83) | - | - | 348 (23.0) | 0.81 | - | - | |
| Yen et al. [161] (2018) | 1,716 | Taiwan | 908 (52.9) | 0.68 (0.66–0.70) | 1.4 | 72.4/63.2 | 745 (43.4) | 0.68 (0.66–0.70) | 1.6 | 67.1/68.8 | 436 (25.4) | 0.70 (0.68–0.73) | 2.2 | 64.9/75.4 | |
| Mada et al. [162] (2020) | 496 | US | 312 (62.9) | 0.48 (0.39–0.58) | - | - | 168 (33.9) | 0.52 (0.42–0.62) | ≤0.7 | 52.0/59.0 | 74 (14.9) | 0.53 (0.42–0.64) | - | - | |
| ≥1.0 | 36.0/73.0 | ||||||||||||||
| Forns Index | Forns et al. [13] (2002) | 476 | Spain | 118 (24.8) | 0.86 | <4.2 | 94.0/51.0 | - | - | - | - | - | - | - | - |
| >6.9 | 30.0/95.0 | ||||||||||||||
| Martinez et al. [158] (2011) | 340 | Spain | 229 (67.3) | 0.83 (0.78–0.87) | <4.2 | 89.0/58.0 | 155 (45.5) | 0.85 (0.81–0.89) | - | - | 124 (36.4) | 0.87 (0.83–0.91) | - | - | |
| <6.9 | 44.0/93.0 | ||||||||||||||
| Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.75 (0.71–0.80) | - | - | - | - | - | - | - | - | - | - | |
| ELF* | Rosen-berg et al. [3] (2004) | 496 | UK | - | 0.77 (0.69–0.84) | 0.063 | 95.0/29.0 | - | - | - | - | - | - | - | - |
| ELF† | Martinez et al. [158] (2011) | 340 | Spain | 229 (67.3) | 0.81 (0.76–0.86) | ≤-0.45 | 90.0/52.0 | 155 (45.5) | 0.83 (0.79–0.87) | - | - | 124 (36.4) | 0.82 (0.78–0.87) | ≤0.06 | 90.0/53.0 |
| ≤1.07 | 47.0/90.0 | ≤1.73 | 52.0/90.0 | ||||||||||||
| ELF* | Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.78 (0.74–0.83) | - | - | - | - | - | - | 61 (14.0) | 0.88 (0.83–0.92) | - | - |
| ELF‡ | Lichting-hagen et al. [164] (2013) | 79 | Germany | 68 (86.1) | 0.9 | 7.7 | 100.0/12.5 | - | - | - | - | - | - | - | - |
| 7.8 | 84.6/75.0 | ||||||||||||||
| 11.3 | 64.1/97.5 | ||||||||||||||
| FibroTest | Imbert-Bismut et al. [166] (2001) | 339 | France | 78 (80.0) | 0.87 | 0.48 | 75.0/85.0 | - | - | - | - | - | - | - | - |
| Poynard et al. [165] (2012) | 1,289 | France | 788 (61.0) | 0.75 (0.72–0.77) | 0.48 | 66.0/85.0 | - | - | - | - | 199 (15.0) | 0.85 (0.82–0.88) | 0.74. | 68.0/89.0 | |
| Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.80 (0.75–0.84) | 0.48 | 75.8/66.2 | - | - | - | - | 61 (14.0) | 0.86 (0.83–0.90) | 0.74 | 71.4/81.0 | |
| Fibro-Meter | Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.82 (0.78–0.86) | 0.411 | 87.6/56.4 | - | - | - | - | 61 (14.0) | 0.89 (0.86–0.93) | 0.88 | 69.6/88.7 |
| Hepascore | Zarski et al. [159] (2012) | 436 | France | 200 (45.9) | 0.82 (0.78–0.85) | 0.5 | 74.7/72.5 | - | - | - | - | 61 (14.0) | 0.89 (0.86–0.93) | 0.84 | 76.8/81.3 |
CHC, chronic hepatitis C; FIB-4, fibrosis-4; APRI, aspartate aminotransferase-to-platelet ratio index; ELF, enhanced liver fibrosis; AUC, area under the curve; CI, confidence interval.
*
–6.38–(ln(age)×0.14)+(ln(HA)×0.616)+(ln(P3NP)×0.586)+(ln(TIMP1)×0.472).
†
–7.412+(ln(HA)×0.681)+(ln(P3NP)×0.775)+(ln(TIMP1)×0.494).
‡
2.494+0.846×ln(HA)+0.735×ln(P3NP)+0.391×ln(TIMP1).