Table 2.
Summary of Biomarkers for Diagnosis of NASH.
| Noninvasive test | Parameters | Study subjects | Result (AUROC) | Diagnostic accuracy | References |
|---|---|---|---|---|---|
| Age, gender, AST, BMI, HA, AST:ALT ratio | 80 patients with NAFLD; 39 patients with simple steatosis, 41 patients with NASH | 0.76 | Sensitivity: 74%, specificity: 66% | 54, 12 | |
| Hypertension, DM, AST > 27, ALT > 27, sleep apnoea, nonblack race | 200 patients undergoing bariatric surgery: 64 patients had NASH. | 0.8 | ≥6 PPV: 87–93% ≤2 NPV: 93–80% |
51, 11 | |
| DM, TG > 150 mg/dl, ALT, obstructive sleep apnoea | 253 patients with morbid obesity | 0.76 | ≤1 NPV: 90% ≥4 PPV: 60% |
17, 14 | |
| Resistin, cleaved CK18, adiponectin | 101 patients with NAFLD | 0.91 in the test group, 0.73 in the validation set | Cut-off = 0.4320 Sensitivity: 72%, specificity: 91% |
23, 24 | |
| CK18, ALT, platelets, triglycerides | 95 patients with NAFLD | 0.92 | Cut-off = 0.361 Sensitivity: 89%, specificity: 86% |
24, 27 | |
| Adiponectin, leptin, ghrelin | 82 patients with morbid obesity | 0.79 | Sensitivity: 82%, specificity: 76% | 27, 35 | |
| Terminal peptide of procollagen III | 136 patients with NAFLD | 0.83 in the test group, 0.78 in the validation set | Cut-off = 6.6, NPV: 85–100% Cut-off = 11.0, PPV: 80–100% |
47, 69 | |
| CK18, soluble Fas | 177 patients with NAFLD | 0.93 in the test group, 0.79 in the validation set | Sensitivity: 88%, specificity: 89% | 22, 26 | |
| CK18 fragments | 139 patients with NAFLD | 0.83 | 19, 21 | ||
| CK18 fragment (CK18-M30, CK18-M65, CK18-M65ED) pooled analysis | 2415 patients with NAFLD | 0.82 | CK18-M30 Sensitivity: 68%, specificity: 74% |
20, 22 | |
| NashTest | 13 variables: age, sex, weight, height, TG, cholesterol, α2-macroglobulin, ApoA1, AST, ALT, haptoglobin, GGT, BR | 257 patients (17% patients with NASH) and 383 controls | 0.79 | Specificity: 94% (PPV = 66%), and sensitivity: 33% (NPV = 81%) | 56, 13 |
| NASH Diagnostics |
CK18-M65, CK18-M30, resistin and adiponectin | 101 patients with NAFLD, 69 patients in the test group, (32% of patients with NASH) 32 patients in the validation group | AUROC: 0.91 | Sensitivity: 96%, specificity: 70% | 43, 24 |
| NAFIC score | Ferritin, fasting insulin, type Ⅳ collagen S | 619 patients with NAFLD; 177 patients in the test group (95 patients with NASH), 442 patients in the validation group | 0.85 in the test group, 0.78 in the validation group | 57, 44 | |
| Nice model | CK18-M30, ALT, presence of metabolic syndrome | 454 patients obese, 310 patients in the test group, 154 patients in the validation group | 0.88 in the test group, 0.83 in the validation set | 58, 45 | |
| HAIR | Insulin resistance, hypertension and ALT | 105 patients with obesity undergoing bariatric surgery, including 26 with NASH | Sensitivity: 80%, specificity: 89% | 48, 36 | |
| Novel combinations | Collagen Pro-C3, CK18 (M30) fragments, AST, ALT, procollagen III N-terminal peptide, acetyl-HMGB-1 and PNPLA3 rs738409 | 374 patients with NAFLD | 0.87 | Sensitivity: 71%, specificity: 87% | 26, 29 |
HAIR, hypertension, ALT, insulin resistance; PPV, positive predictive value; NPV, negative predictive value; GGT, gamma-glutamyl transferase; AUROC, area under the receiver operating characteristic curve; AST, aspartate aminotransferase; ALT, alanine aminotransferase; BMI, body mass index; BR, bilirubin; CK, cytokeratin; DM, diabetes mellitus; HA, hyaluronic acid; NASH, nonalcoholic steatohepatitis; NAFLD, nonalcoholic fatty liver disease; PNPLA, patatin-like phospholipase domain–containing protein A; TG, triglyceride.