Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease

Table 6 Imaging biomarkers for the detection of nonalcoholic steatohepatitis and 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
Yang et al[106], 2022	CAP [dB/m]	China	Predicting NASH in children with obesity	NAFLD (n = 61), Non-NAFLD (n = 59), NAFL (n = 44), NASH (n = 17)	US	> 276	0.722 (0.602-0.843)	70.6	72.8			0.0058
Chaidez et al[105], 2022	LSM	United States	F0-F2 vs F3-F6 (Ishak)	Total (n = 206)	Biopsy		0.73 (0.64-0.81)
Chaidez et al[105], 2022	LSM	United States	F0-F2 vs F3-F6 (Ishak)	NAFLD (n = 116)	Biopsy		0.77 (0.67-0.88)
Chaidez et al[105], 2022	LSM	United States	F0-F2 vs F3-F6 (Ishak)	Non-NAFLD (n = 90)	Biopsy		0.70 (0.56-0.83)
Yang et al[106], 2022	LSM [kPa]	China	Predicting NASH in children with obesity	NAFLD (n = 61), Non-NAFLD (n = 59), NAFL (n = 44), NASH (n = 17)	US	> 5.15	0.725 (0.611-0.839)	64.7	65			0.0048
Xanthakos et al[132], 2014	MRE [kPa]	United States	F2-F4 vs F0-F1	Chronic liver disease (n = 35; 27 with NAFLD); F0-F1 (n = 27), F2-F4 (n = 8)	Biopsy	2.71	0.92 (0.79-1.00)	88	85			0.02
Schwimmer et al[133], 2017	MRE [kPa]	United States	Any Fibrosis (F0 vs F1-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 2.77	0.77	44.4	90.7	76.2	71
Schwimmer et al[133], 2017	MRE [kPa]	United States	Any Fibrosis (F0 vs F1-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 2.69	0.79	47.2	88.9	73.9	71.6
Schwimmer et al[133], 2017	MRE [kPa]	United States	Any Fibrosis (F0 vs F1-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 2.78	0.772	44.4	90.7	76.2	71
Schwimmer et al[133], 2017	MRE [kPa]	United States	Advanced Fibrosis (F0-2 vs F3-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 3.05	0.925 (0.539-0.989)	50	91.7	30	96.2
Schwimmer et al[133], 2017	MRE [kPa]	United States	Advanced Fibrosis (F0-2 vs F3-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 3.03	0.879 (0.539-0.898)	33.3	94	28.6	95.2
Schwimmer et al[133], 2017	MRE [kPa]	United States	Advanced Fibrosis (F0-2 vs F3-4)	F0 (n = 54), F1 (n = 24), F2 (n = 6), F3 (n = 5), F4 (n = 1)	Biopsy	≥ 3.33	0.894 (0.682-0.959)	33.3	90.5	20	95
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-1 vs ≥ stage 2 fibrosis in total cohort	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy	2.27	0.70 (0.59-0.81)	68.6	74.3
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-1 vs ≥ stage 2 fibrosis in total cohort	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy	1.67		35.3	91.4
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-2 from ≥ stage 3 fibrosis	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy	6.55	0.90 (0.83-0.97)	85.7	77.8
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-2 from ≥ stage 3 fibrosis	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy	5.41		64.3	93.1
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-1 vs ≥ stage 2 fibrosis in patients with steatosis (n = 41)	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy		0.53 (0.35-0.71)
Trout et al[134], 2018	MRE [kPa]	United States	Ludwig stage 0-1 vs ≥ stage 2 fibrosis in patients without steatosis (n = 45)	Total (n = 86; 48 with NAFLD), Ludwig ≥ stage 2 (n = 51), steatosis (n = 44)	Biopsy		0.82 (0.67-0.96)
Alkhouri et al[108], 2012	PNFI	Italy	≥ F2	F0-F1 (n = 57), F2-F3 (n = 10)	Biopsy	8.2	0.747 (0.632-0.820)					0.005
Nobili et al[107], 2008	TE [kPa]	Italy	≥ F1	F0 (n = 11), F1 (n = 27), F2 (n = 7), F3-4 (n = 5)	Biopsy	5.1	0.97 (0.90-0.99)	97	91	97	91
Nobili et al[107], 2008	TE [kPa]	Italy	≥ F2	F0 (n = 11), F1 (n = 27), F2 (n = 7), F3-4 (n = 5)	Biopsy	7.4	0.99 (0.92-0.99)	100	92	80	100
Nobili et al[107], 2008	TE [kPa]	Italy	≥ F3	F0 (n = 11), F1 (n = 27), F2 (n = 7), F3-4 (n = 5)	Biopsy	10.2	1.00 (0.94-1.00)	100	100	100	100
Alkhouri et al[108], 2012	TE [kPa]	Italy	≥ F2	F0-F1 (n = 57), F2-F3 (n = 10)	Biopsy	8.6	1.00 (0.981-1.00)

AUROC: Area under the receiving operating characteristic; CAP: Controlled attenuation parameter; CI: Confidence interval; DX: Diagnosis; F: Fibrosis stage; LSM: Liver stiffness measurement; MRE: Magnetic resonance elastography; NAFL: Nonalcoholic fatty liver; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; NPV: Negative predictive value; PNFI: Proton density fat fraction index; PPV: Positive predictive value; Sens: Sensitivity; Spec: Specificity; TE: Transient elastography.