Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease

Table 7 Composite scores for the detection of nonalcoholic steatohepatitis

Ref.	Scores	Country	Categories Tested	Sample size (n)	Dx	Cutoff	AUROC (95%CI)	Sens (%)	Spec (%)	PPV (%)	NPV (%)
Manco et al[57], 2022	Ang-2 + CK18	Italy	Diagnosing NASH	NAFLD (n = 76), healthy controls (n = 28, by ultrasound)	Biopsy			71.4	100	100	80.4
Mosca et al[101], 2019	APRI	Italy	Definite NASH vs No/Borderline NASH	No/borderline NASH (n = 115), definite NASH (n = 89)	Biopsy	> 0.24	0.6826	58	72	69	62
Walenbergh et al[70], 2015	CatD + CK18	Italy	Steatosis from NASH	NASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)	Biopsy		0.998
Walenbergh et al[70], 2015	CatD + CK18	Italy	Borderline NASH vs definite NASH	NASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)	Biopsy		0.858
Walenbergh et al[70], 2015	CatD + CK18	Italy	Steatosis + Borderline NASH vs NASH	NASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)	Biopsy		0.892
Walenbergh et al[70], 2015	CatD + CK18	Italy	Steatosis vs borderline NASH + NASH	NASH (n = 26), borderline NASH (n = 51), steatosis (n = 19), obese (n = 96)	Biopsy		0.85
Mosca et al[101], 2019	FIB-4	Italy	Definite NASH vs No/Borderline NASH	No/borderline NASH (n = 115), definite NASH (n = 89)	Biopsy	> 0.22	0.6369	48	73	65	58
Arsik et al[54], 2018	Mean ALT over 96 wk	United States	NASH	Fibrosis (n = 128), NASH (n = 131)	Biopsy		81.84	80.5	83
Arsik et al[54], 2018	Mean ALT over 96 wk	United States	NASH + Fibrosis	Fibrosis (n = 128), NASH (n = 131)	Biopsy		77.78	71.8	80.8
Kwon et al[137], 2022	P1NP/ALP ratio	Korea	Presence of steatohepatitis	NAFLD (n = 60)	US	1.46	0.788 (0.658-0.918)	78.8	81.3
Kwon et al[137], 2022	P1NP/ALP ratio × ALT	Korea	Presence of steatohepatitis	NAFLD (n = 60)	US	119.08	0.894 (0.812-0.977)	82.6	92.9
Kwon et al[137], 2022	P1NP/osteocalcin ratio	Korea	Presence of steatohepatitis	NAFLD (n = 60)	US	3.54	0.782 (0.647-0.918)	80.9	76.9
Kwon et al[137], 2022	P1NP/Osteocalcin ratio × ALT	Korea	Presence of steatohepatitis	NAFLD (n = 60)	US	305.38	0.939 (0.88-0.999)	83	92.3
Manco et al[95], 2007	Risk Score	Italy	Predicting NAFLD Activity Score	NAFLD (n = 72), F0 (n = 31), F1 (n = 41)	Biopsy	≤ 12.9	0.985	9	2	4	33
Manco et al[95], 2007	Risk Score	Italy	Predicting NAFLD Activity Score	NAFLD (n = 72), F0 (n = 31), F1 (n = 41)	Biopsy	≥ 13.5		81	92	82	92

ALP: Alkaline phosphatase; ALT: Alanine transaminase; Ang-2: Angiopoietin-2; APRI: AST to platelet ratio index; AUROC: Area under the receiving operating characteristic; CatD: Cathepsin D; CK18: Cytokeratin 18; CI: Confidence interval; Dx: Diagnosis; F: Fibrosis stage; FIB-4: Fibrosis-4; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; P1NP: Procollagen type 1 amino-terminal propeptide; PPV: Positive predictive value; NPV: Negative predictive value; Risk Score: 0.440 + (1.454 × ln leptin) + (4.617 × ln TNF-α); Sens: Sensitivity; Spec: Specificity; TNF-α: Tumor necrosis factor-alpha; US: Ultrasound.