Table 3.
Diagnostic Accuracy of NITs for Detection of Fibrosis Stage ≥F2 in Patients With CHC
| Test | Number of Studies | Cutoff | Summary Sensitivity | 95% CI | Summary Specificity | 95% CI | Statistics |
|---|---|---|---|---|---|---|---|
| Indirect noninvasive serum tests | |||||||
| APRI (low cutoff) | 47 | 0.4-0.7 | 0.82 | 0.77-0.86 | 0.57 | 0.49-0.65 | Bivariate random-effects model with correlation between sensitivity and specificity |
| APRI (high cutoff) | 36 | 1.5 | 0.39 | 0.32-0.47 | 0.92 | 0.89-0.95 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Age_Platelet index | 1 | 3 | 0.58 | 0.46-0.70 | 0.70 | 0.64-0.84 | Single study |
| AST_ALT_ratio | 7 | 0.6-1 | 0.44 | 0.27-0.63 | 0.71 | 0.62-0.78 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Cirrhosis discriminant score | 1 | 6 | 0.66 | 0.59-0.73 | 0.49 | 0.34-0.64 | Single study |
| FIB-4 (low cutoff) | 11 | 0.6-1.45 | 0.89 | 0.79-0.95 | 0.42 | 0.25-0.61 | Random-effects model for sensitivity and specificity without correlation |
| FIB-4 (high cutoff) | 9 | 1-3.25 | 0.59 | 0.43-0.73 | 0.74 | 0.56-0.87 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Forns index (low cutoff) | 18 | 4.2-4.5 | 0.88 | 0.83-0.91 | 0.40 | 0.33-0.48 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Forns index (high cutoff) | 15 | 6.9-8.7 | 0.35 | 0.29-0.41 | 0.96 | 0.92-0.98 | Bivariate random-effects model with correlation between sensitivity and specificity |
| FibroQ | 1 | 1.6 | 0.78 | 0.71-0.83 | 0.66 | 0.51-0.78 | Single study |
| Fibrosis probability index (low cutoff) | 2 | 0.2 | 0.91 | 0.83-0.96 | 0.45 | 0.34-0.57 | Fixed-effects model for sensitivity and specificity without correlation |
| Fibrosis probability index (high cutoff) | 2 | 0.8 | 0.42 | 0.32-0.54 | 0.95 | 0.87-0.98 | Fixed-effects model for sensitivity and specificity without correlation |
| GUCI | 3 | 0.33-1.1 | 0.65 | 0.1-1.00 | 0.79 | 0.03-1.00 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Kings | 1 | 9.87 | 0.84 | 0.75-0.9 | 0.70 | 0.61-0.79 | Single study |
| Kings (low cutoff) | 1 | 4.46 | 0.62 | 0.55-0.69 | 0.81 | 0.76-0.86 | Single study |
| Kings (high cutoff) | 1 | 12.3 | 0.58 | 0.51-0.65 | 0.79 | 0.73-0.83 | Single study |
| Lok's model | 4 | 0.2-1.67 | 0.67 | 0.55-0.77 | 0.55 | 0.29-0.78 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Platelets | 10 | 48-182 | 0.50 | 0.41-0.59 | 0.89 | 0.83-0.93 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Pohl index | 2 | Positive | 0.06 | 0.04-0.1 | 0.99 | 0.93-1.00 | Fixed-effects model for sensitivity and specificity without correlation |
| Direct serum noninvasive serum tests | |||||||
| Aminopyrine breath test | 1 | 8.1 | 0.73 | 0.57-0.85 | 0.74 | 0.58-0.85 | Single study |
| Hyaluronic acid | 8 | 34-110 ng/mL | 0.75 | 0.64-0.83 | 0.75 | 0.68-0.82 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Hepascore | 10 | 0.31-0.5 | 0.73 | 0.66-0.79 | 0.73 | 0.65-0.79 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Hepascore (high cutoff) | 1 | 0.84 | 0.33 | 0.24-0.43 | 0.92 | 0.85-0.96 | Single study |
| MP3 | 1 | 0.3 | 0.82 | 0.73-0.89 | 0.73 | 0.63-0.81 | Single study |
| PIIINP | 2 | 8.3-9.1 | 0.78 | 0.63-0.87 | 0.76 | 0.54-0.90 | Fixed-effects model for sensitivity and specificity without correlation |
| PIIINP/MMP-1 index | 1 | 0.3 | 0.65 | 0.55-0.75 | 0.85 | 0.77-0.90 | Single study |
| Type IV collagen | 5 | 110-298 | 0.88 | 0.71-0.96 | 0.73 | 0.63-0.82 | Random-effects model for sensitivity and specificity without correlation |
| YKL-40 (low cutoff) | 1 | 290 | 0.80 | 0.66-0.89 | 0.33 | 0.26-0.41 | Single study |
| YKL-40 (high cutoff) | 1 | 540 | 0.33 | 0.21-0.48 | 0.80 | 0.73-0.86 | Single study |
| Commercial noninvasive serum tests | |||||||
| ELF | 1 | 8.75 | 0.84 | 0.69-0.92 | 0.70 | 0.52-0.83 | Single study |
| ELF (low cutoff) | 1 | 9.55 | 0.90 | 0.85-093 | 0.52 | 0.43-0.61 | Single study |
| ELF (high cutoff) | 1 | 11.07 | 0.47 | 0.41-0.54 | 0.90 | 0.83-0.94 | Single study |
| FibroIndex (low cutoff) | 4 | 1.25 | 0.83 | 0.15-0.99 | 0.57 | 0.22-0.86 | Random-effects model for sensitivity and specificity without correlation |
| FibroIndex (high cutoff) | 4 | 2.25 | 0.24 | 0.11-0.43 | 0.98 | 0.93-1.00 | Random-effects model for sensitivity and fixed-effect model for specificity without correlation |
| FibroMeter | 4 | 0.42-0.57 | 0.79 | 0.69-0.86 | 0.73 | 0.63-0.81 | Bivariate random-effects model with correlation between sensitivity and specificity |
| FibroSpect II | 5 | 42-72 | 0.78 | 0.49-0.93 | 0.71 | 0.59-0.80 | Random-effects model for sensitivity and specificity without correlation |
| FibroTest | 17 | 0.32-0.53 | 0.68 | 0.58-0.77 | 0.72 | 0.70-0.77 | Bivariate random-effects model with correlation between sensitivity and specificity |
| FibroTest (low cut-off) | 7 | 0.1-0.3 | 0.91 | 0.86-0.94 | 0.41 | 0.37-0.46 | Random-effects model for sensitivity and specificity without correlation |
| Fibrotest (high cutoff) | 10 | 0.6-0.7 | 0.57 | 0.46-0.67 | 0.85 | 0.74-0.92 | Bivariate random-effects model with correlation between sensitivity and specificity |
| Imaging modalities | |||||||
| ARFI | 3 | 1.21-1.34 | 0.79 | 0.75-0.83 | 0.89 | 0.84-0.93 | Fixed-effects model for sensitivity and specificity without correlation |
| MRE | 3 | — | 0.94 | 0.13-1 | 0.92 | 0.72-0.98 | Model 3; random effects for sensitivity and fixed effect for specificity |
| PLT_spleen ratio | 3 | 1750-2200 | 0.88 | 0.62-0.99 | 0.73 | 0.41-0.99 | Bivariate random-effects model with correlation between sensitivity and specificity |
| FibroScan | 37 | 5.2-10.1 | 0.79 | 0.74-0.84 | 0.83 | 0.77-0.88 | Bivariate random-effects model with correlation between sensitivity and specificity |
| US | 3 | — | 0.35 | 0.14-0.63 | 0.86 | 0.59-0.96 | Metadas |
| US_SAPI | 3 | — | 0.74 | 0.69-0.79 | 0.79 | 0.72-0.85 | Model 5; fixed-effect model for both |
| US_SAPI (high cutoff) | 2 | — | 0.61 | 0.54-0.68 | 0.96 | 0.9-0.98 | Model 5; fixed-effect model for both |
| US_SAPI_F2 (low cutoff) | 2 | — | 0.94 | 0.9-0.97 | 0.39 | 0.31-0.49 | Model 5; fixed-effect model for both |
| Combination of fibrosis noninvasive tests algorithms | |||||||
| Bordeaux | 1 | — | 0.88 | 0.85-0.91 | 0.89 | 0.85-0.92 | Single study |
| Fibropaca | 1 | — | 0.85 | 0.81-0.89 | 0.90 | 0.86-0.93 | Single study |
| Leroy | 1 | — | 0.90 | 0.79-0.96 | 0.98 | 0.95-0.99 | Single study |
| SAFE | 4 | — | 1.00 | 1.00-1.00 | 0.81 | 0.80-0.83 | Fixed-effects model for sensitivity and specificity without correlation |
Bordeaux consists of the synchronous use of FibroTest and FibroScan, followed by liver biopsy in cases of discordance. Fibropaca consists of the synchronous use of FibroTest plus APRI and/or Forns, followed by liver biopsy in cases of discordance. Leroy consists of the synchronous use of FibroTest plus APRI, followed by liver biopsy in patients with intermediate values. SAFE is a sequential algorithm that consists of APRI as the initial test followed by FibroTest in the indeterminate fibrosis cases or liver biopsy in patients with low risk of fibrosis according to APRI.
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; GUCI, Göteborg University Cirrhosis Index; MP3 score, combination of PIIINP and MMP-1; PIIINP, N-terminal procollagen III; MMP-1, matrix metalloproteinase 1; YKL-40, human cartilage glycoprotein 39; ELF, enhanced liver fibrosis score; ARFI, acoustic radiation force impulse; PLT_spleen ratio, platelet to spleen size ratio; US, ultrasound; US_SAPI, ultrasonographic evaluation of the splenic artery pulsatility index; CI, confidence interval.