Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

Table 1 Risk of bias assessment and concerns about applicability according to Quality Assessment of Diagnostic Accuracy Studies tool for quality assessment of prognostic accuracy studies

Ref.	Risk of bias				Applicability concerns
	Patients selection	Index test	Reference standard	Flow and timing	Patients selection	Index test	Reference standard
Ainora et al[5], 2023	Low	Unclear	Low	Low	Low	Low	Low
Dong et al[15], 2023	Unclear	Low	Low	Low	Low	Low	Low
Wildner et al[23], 2019	High	Unclear	Unclear	High	Low	Low	Low
Wildner et al[17], 2014	High	High	Low	High	Low	Low	Low

Table 2 Study characteristics of included publications

Ref.	Study design	Outcome	No. patients	Ultrasound contrast agent	Software for analysis of time-intensity curves
Ainora et al[5], 2023, Italy	Prospective	HCC vs ICC	82	SonoVue®	Vuebox®
Dong et al[15], 2023, China	Retrospective	HCC vs ICC	54	SonoVue®	Vuebox®
Wildner et al[23], 2019, Germany	Prospective	HCC vs ICC vs metastases vs FNH	148	SonoVue®	Vuebox®
Wildner et al[17], 2014, Germany	Prospective	HCC vs ICC	43	SonoVue®	Vuebox®

FNH: Focal nodular hyperplasia; HCC: Hepatocellular carcinoma; ICC: Intracellular cholangiocarcinoma.

Table 3 Baseline patients’ characteristics in the included publications

Ref.	Age (yr)	Sex (male/female)	Origin of the study population	No. HCC	No. non HCC
Ainora et al[5], 2023	68 ± 11	55/27	Cirrhotic and non-cirrhotic patients	38	44
Dong et al[15], 2023	59.4 ± 8.6 (ICC)	27/27	Non-cirrhotic patients	24	30
	60.9 ± 12.1 (HCC)
Wildner et al[23], 2019	63.8 ± 12.6	84/64	Cirrhotic and non-cirrhotic patients	41	107
Wildner et al[17], 2014	67	30/13	Cirrhotic and non-cirrhotic patients	23	20

HCC: Hepatocellular carcinoma; ICC: Intracellular cholangiocarcinoma.

Table 4 Dynamic continuous variables of hepatocellular carcinoma vs intracellular cholangiocarcinoma lesions in the included publications

	Ainora et al[5], 2023		Dong et al[15], 2023
	HCC (n = 38)	ICC (n = 44)	HCC (n = 24)	ICC (n = 30)
Rise time lesion (s)	10.9 ± 3.8	8.1 ± 4.1	11.9 ± 5.3	7.5 ± 3.0
Fall time lesion (s)	37.5 ± 19.5	35.4 ± 23.9	27.7 ± 10.8	14.9 ± 5.9
mTTL lesion (s)	67.0 ± 52.0	42.9 ± 46.1	68.9 ± 32.4	42.2 ± 18.0
TTP lesion (s)	12.5 ± 4.3	9.1 ± 5.8	17.6 ± 9.6	12.8 ± 6.4
PE percent change	0.66 ± 1.35	-0.04 ± 1.38	1.28 ± 0.47	1.16 ± 0.90
WiR percent change	2.41 ± 3.96	1.32 ± 1.91	2.33 ± 1.19	2.38 ± 2.33
WiAUC percent change	-0.22 ± 0.72	-0.52 ± 0.36	0.79 ± 0.45	0.61 ± 0.51
WoAUC percent change	-0.11 ± 0.74	-0.41 ± 0.53	0.85 ± 0.53	0.53 ± 0.42
WiWoAUC percent change	-0.13 ± 0.70	-0.39 ± 0.39	0.83 ± 0.50	0.55 ± 0.44

HCC: Hepatocellular carcinoma; ICC: Intracellular cholangiocarcinoma; mTTL: Mean transit time local; TTP: Time to peak; PE: Peak enhancement; WiR: Wash-in rate; WiAUC: Wash-in area under the curve; WiWoAUC: Wash-in and wash-out area under the curve; WoAUC: Wash-out area under the curve.