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. 2020 Apr 17;9(4):1005. doi: 10.3390/cells9041005

Table 1.

Various emerging modalities for nonalcoholic steatohepatitis (NASH) minimally invasive/noninvasive diagnosis: (A) blood clinical biochemistry liver function tests with liver histology as comparator; (B) physical tests US-based or not.

A. Blood Liver Funtion Tests Parameter Measured Pros Cons AUROC
ELF panel [39] Hyaluronic acid (HA),
Tissue inhibitor metalloproteinase 1 (TIMP1), and Aminoterminal peptide of procollagen 3 (PIIINP).
Feasible in large number of subjects
Good outcome correlation
Commercial test not routinely available 0.93 in adults
0.99 in pediatric patients
Pro-C3 [42] Pro collagen III Able to discriminate simple fatty liver from NASH and different stages of fibrosis Commercial test 0.86
NASH NIS4 [44] MicroRNA 34a-5p; alpha2 macrogobulin (A2M), Haemooglobin A1c (HbA1c), and Chitinase-3-like protein 1 (CHI3L1 also known as YKL40) This tool can enrich the selection of patients—candidate to experimental trials—with active NASH and significant fibrosis Commercial test;
performances might vary according to the baseline characteristics of the studied population
0.82
Lipidomic serum test §
(OWLiver) [45]
Two subsequent analyses of 11 and 20 triglycerides panel to be used in adults with BMI > 25 Able to discriminate normal liver form NAFLD and NAFLD from NASH Commercial test performed in a centralized laboratory 0.79 or 0.81 (according to inclusion or exclusion of patients with glucose >136 mg/dl)
B.US-Based Physical Tests Parameter Measured Pros Cons AUROC
TE [47,48] Liver stiffness Short processing time and
outpatient clinic setting
Measurement failures reported in up to 20% and
XL probe required in obese patients
0.95 for F4
0.93 for F3
0.84 for F2 fibrosis
Point shear wave elastgraphy (ARFI) [49] Liver stiffness Short processing and
outclinic setting
Quality criteria not well defined,
lack of large-scale studies
0.78–0.89 for F4
0.74–0.97 for F3
0.70–0.83
for F2 fibrosis
B. Not US-Based physical tests Parameter Measured Pros Cons AUROC
MRE [50,51] Liver stiffness Not influenced by BMI and inflammation Long processing,
expensive, and
not largely available
0.88–0.97
for F4
0.89–0.96
for F3
0.86–0.89
for F2
LiverMultiScan
(multiparametric resonance) [52]
Fibrosis and inflammation mapping Quick and no contrast agent required Further validation studies required 0.85
for F4

§ compared to histology.