Table 2.
Accuracy of some biomarkers and diagnostic panels for non-alcoholic steatohepatitis (NASH) (inflammation, oxidative stress, apoptosis) and advanced liver fibrosis (bottom). A wide range of biomarkers and panels have been tested. In general, studies are small and need further validation. The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curves vary depending on the defined cut-off point
| Test | AUROC (%) | Cut-off value | Sensitivity (%) | Specificity (%) | PPV | NPV |
|---|---|---|---|---|---|---|
| TNFα mRNA [117] | 0.685 | 100 ng/mL | 66.7 | 74.1 | ||
| IL-6 [118] | 0.817 | 4.6 pg/mL | 58.1 | 100 | ||
| hsCRP [119] | 0.906 | 3.5 | 82 | 88 | ||
| Ferritin [120] | 0.82 0.732 |
240 ng/mL 196 |
91 64.2 |
70 76.5 |
||
| Adiponectin [121] | 0 .765 | <4 μg/mL | 68 | 79 | ||
| CK-18 | 0.93 [122] | 395 U/L | 85.7 | 99 | ||
| 0.83a [45] | 225 U/L | 70 | 82 | 84 | 73 | |
| 250 U/L | 60 | 93 | 95 | 69 | ||
| 300 U/L | 53 | 100 | 100 | 67 | ||
| 0.84b [68] | 121–479 | 78 | 87 | |||
| 95 % CI 64–92 | ||||||
| Hyaluronic acid [123, 124] | 0.797 | 43 ng/mL | 97.1 | |||
| NAFLD diagnostic panel (diabetes, gender, BMI, TG, CK-18) [47] | 0.81 0.85 |
0.221 0.3641 0.6183 ≤1.455c >0.676d |
91.2 79.4 44.1 90 67 |
47.4 73.7 92.1 60 97 |
60.8 73 83.3 |
85.7 80 64.8 |
| Hyaluronic acid [125] | 0.975 | 148.8 ng/mL | 97.5 | 95.7 | ||
| FIB4 index (age, ALT, AST, platelet count) [125, 126] | 0.802 | <1.30 | 74 | 71 | 43 | 90 |
| ELF (HA, TIMP1, PIIINP) [51, 68] | 0.90 0.76e 0.82f 0.90g |
0.3576 −0.2070 −0.1068 0.3576 |
80 61 70 80 |
90 80 80 90 |
71 | 94 |
| Fibrotest (a2macroglobuline, haptoglobin, GGT, tot BB, ApoA1) [127] | 0.81 | 0.3 0.7 |
77 15 |
77 98 |
54 73 |
90 76 |
| NAFLD fibrosis score (age, hyperglycemia, BMI, platelet count, albumin, AAR) [9, 16, 68] | 0.84 0.85h 95 % CI 0.81–0.90 |
≤1.455 >0.676 ≤1.455 >0.676 |
82 51 90 (86–95) 64 (59–70) |
77 98 60 (56–65) 97 (94–99) |
56 90 |
93 85 |
PPV positive predictive value, PNV negative predictive value, CK-18 cytokeratin 18, BMI body mass index, TG fasting triglycerides, ALT alanine aminotransferase, AST aspartate aminotransferase, ELF enhanced liver fibrosis panel, HA hyaluronic acid, TIMP1 tissue inhibitor of metalloproteinase 1, PIIINP amino-terminal propeptide of type III collagen, AAR AST/ALT ratio
aAccuracy for differentiating patients with NASH from those with simple steatosis with three different cut points: 225, 250, and 300 U/L. For every 50-U/L increase in the plasma level of CK-18, the likelihood of having NASH increased 30 % [OR (95 % CI) 1.3 (1.1–1.4)]. CK-18 fragment levels were significantly higher in patients with fibrosis as compared to those without fibrosis [45]
bSummary estimates of nine studies [68]
cTo exclude advanced fibrosis
dTo identify the presence of advanced fibrosis
e95 % CI 0.69–0.83 to identify any fibrosis (stage 1–4)
f95 % CI 0.75–0.88 to identify ≥F2
g95 % CI 0.84–0.96 to identify ≥F3
hSummary estimates of 13 studies. To identify ≥F3