Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease

Table 4 Serological biomarkers for the detection of fibrosis in nonalcoholic fatty liver disease

Ref.	Marker	Country	Categories Tested	Sample size (n)	Dx	Cutoff	AUROC (95%CI)	Sens (%)	Spec (%)	PPV (%)	NPV (%)	P value
Mandelia et al[84], 2016	CK18	Italy	F1-F3 vs F0	NAFLD (n = 201), F0 (n = 65), F1–F3 (n = 136)	Biopsy		0.75 (0.68-0.81)
Mandelia et al[84], 2016	CK18	Italy	F2-F2 vs F0	NAFLD (n = 201), F0 (n = 65), F1–F3 (n = 136)	Biopsy		0.67 (0.54-0.80)
Mandelia et al[84], 2016	CK18	Italy	F3 vs F0	NAFLD (n = 201), F0 (n = 65), F1–F3 (n = 136)	Biopsy		0.77 (0.56-0.97)
Fitzpatrick et al[67], 2010	CK18 [U/L]	United Kingdom	Significant Fibrosis (≥ F2)	NAFLD (n = 45), healthy controls (n = 13)	Biopsy	200	0.66 (0.5-0.82)	83	40
Lebensztejn et al[80], 2011	CK18 [U/L]	Poland	Fibrosis (F1-F3) vs F0	NAFLD (n = 52), NAFLD with obesity/overweight (n = 42), healthy non-obese controls (n = 25)	Biopsy	210	0.666	79	60	56	82	0.05
Nobili et al[79], 2010	HA [ng/mL]	Italy	F1 and F2+ vs F0	NAFLD (n = 100), F0 (n = 35), ≥ F1 (n = 65)	Biopsy	≥ 1200	0.88 (0.81–0.96)			90	50
Nobili et al[79], 2010	HA [ng/mL]	Italy	F2+ vs F0 and F1	NAFLD (n = 100), F0 (n = 35), ≥ F1 (n = 65)	Biopsy	2100	0.95 (0.91–0.99)			40	90
Lebensztejn et al[80], 2011	HA [ng/mL]	Poland	Fibrosis (F1-F3) vs F0	NAFLD (n = 52), NAFLD with obesity/overweight (n = 42), healthy non-obese controls (n = 25)	Biopsy	19.1	0.672	84	55	52	86	0.04
Lebensztejn et al[80], 2011	HA + CK18	Poland	Fibrosis (F1-F3) vs F0	NAFLD (n = 52), NAFLD with obesity/overweight (n = 42), healthy non-obese controls (n = 25)	Biopsy		0.73	74	79	56	63	0.002
Hamza et al[99], 2016	PIIINP [ng/mL]	Egypt	Presence of steatosis in obese children	Obese with NAFLD (n = 50), obese without NAFLD (n = 5), nonobese healthy controls (n = 30)	US	8.5		74	33
Mosca et al[101], 2019	PIIINP [ng/mL]	Italy	Presence of ≥ F2	No/borderline NASH (n = 115), definite NASH (n = 89)	Biopsy	> 8.89	0.921 (0.87-0.97)	84	94	95	79
Mosca et al[101], 2019	PIIINP [ng/mL]	Italy	Presence of F3	No/borderline NASH (n = 115), definite NASH (n = 89)	Biopsy	> 13.2	0.993 (0.98-1.0)	100	98	78	100

AUROC: Area under the receiver operating characteristic curve; CK18: Cytokeratin 18; CI: Confidence interval; Dx: Diagnosis; F: Fibrosis stage; HA: Hyaluronic acid; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; NPV: Negative predictive value; PIIINP: Amino-terminal propeptide of type III procollagen; PPV: Positive predictive value; Sens: Sensitivity; Spec: Specificity; US: Ultrasound.