Table 1.
Panels of Serum Biomarkers for Fibrosis in NAFLD.
| Biomarker panel | Components | Study subjects | Results (AUROC) | Diagnostic accuracy | References |
|---|---|---|---|---|---|
| AST/ALT | 174 patients with NAFLD | 0.83 in the training set 0.83–0.9 in the validation set |
Cut-off = 0.8, NPV: 93%, PPV: 44% | 57 | |
| Pro-C3 levels | 150 patients with NAFLD | 0.91 | Cut-off >1.6738 82% correctly classified |
71 | |
| Terminal peptide of procollagen III | 136 patients with NAFLD | 0.82 in the training set 0.84 in the validation set |
Cut-off = 6.6 ng/ml, NPV: 95% Cut-off = 11 ng/ml, PPV: 100% |
69 | |
| APRI score | AST, platelets | 541 patients with NAFLD | 0.73 | Cut-off = 1, NPV: 84%, PPV: 37% | 57 |
| FibroTest/FibroSure | Haptoglobin, α2-macroglobulin, apolipoprotein A, bilirubin and GGT | 1202 patients with NAFLD | 0.86 in the training set 0.85 in the validation set |
Cut-off = 0.3, NPV: 98% Cut-off = 0.7, PPV: 60% |
63, 64 |
| ELF test | Hyaluronic acid, PIIINP and TIMP-1 | 1329 patients with NAFLD | 0.87 in the training set 0.90 in the validation set |
67 | |
| NAFLD fibrosis score | Age, BMI, albumin, AST/ALT ratio, hyperglycaemia and platelets | 733 patients with NAFLD | 0.88 in the training set 0.77–0.84 in the validation set |
Cut-off = 0.81, NPV: 78–93% Cut-off = 0.67, PPV: 82–90% |
50, 56, 57, 59 |
| Fibrometer | Age, weight, glucose, AST, ALT, ferritin and platelets | 235 patients with NAFLD | 0.94 in the training set 0.94 in the validation set |
52 | |
| FIB-4 index | Age, AST, ALT and platelets | 686 patients with NAFLD | 0.80 in the training set 0.86 in the validation set |
Cut-off = 1.30, NPV: 90–95% Cut-off = 2.67, PPV: 80% |
50, 57, 59 |
| BARD score | BMI, diabetes and AST/ALT ratio | 1513 patients with NAFLD | 0.81 in the training set 0.77–0.78 in the validation set |
Cut-off = 2, PPV: 27%, NPV: 95–97% | 54, 57, 59 |
| Hepascore | Age, sex, bilirubin, GGT, α2-macroglobulin and hyaluronic acid | 242 patients with NAFLD | 0.81 | Cut-off = 0.37, PPV: 57%, NPV: 92% | 65, 66 |
| FIB-C3 | Pro-C3, age, BMI, diabetes and platelets | 433 patients with NAFLD | 0.86 in the training set 0.85 in the validation set |
72 | |
| FIBROSpect test | a2-macroglubulin, hyaluronic acid and TIMP-1 | 792 patients with NAFLD | 0.87 in the training set 0.85 in the validation set |
Sensitivity: 84–81%, specificity: 72–74%. | 75 |
| Novel combinations | HA, CK18 and TIMP-1 | 180 patients with NAFLD | 0.90 | Sensitivity: 88.2%, specificity: 84.1% | 73 |
ELF, enhanced liver fibrosis; APRI, AST/platelet ratio index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUROC, area under the receiver operating characteristic curve; BMI, body mass index; CK, cytokeratin; INR, international normalised ratio; GGT, gamma-glutamyl transferase; HA, hyaluronic acid; NAFLD, nonalcoholic fatty liver disease; PPV, positive predictive value; NPV, negative predictive value; Pro-C3, C-terminal cleavage site of N-terminal type III collagen propeptide; PIIINP, N-terminal type III collagen propeptide; TIMP-1, tissue inhibitor of metalloproteinase-1.