Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

Table 1 Major Imaging modalities for the diagnosis of hepatocellular carcinoma

Modality		Role	Imaging features of HCC	Sensitivity		Specificity		Advantages	Disadvantages
				All size	≤ 20 mm	All size	≤ 20 mm
US	B-mode US	Screening and surveillance	Nodules with altered echogenicity (hypo- or hyperechoic) and abnormal portal venous and/or arterial blood flow compared with background liver.	51%-67%	26%-49%	80%-100%	67%-80%	1. Real-time, less expensive, no ionizing radiation. 2. CEUS Allows real-time continuous imaging and characterization of the dynamic washin of contrast agents. 3. CEUS Can help resolve indeterminate vascular shunts detected by CT or MRI.	1. Requires recognized expertise to perform good examinations. 2. Sensitive to inter- and intraobserver variabilities. 3. Limited application in obese patients and patients with very cirrhotic heterogeneous livers. 4. US is less accurate compared with CT and MRI for HCC diagnosis. 5. CEUS may demonstrate deteriorated performance for deep, subdiaphragmatic, multiple and treated lesions.
	CEUS	Focal liver lesion characterization, rapid diagnosis	Hyperenhancement in the hepatic arterial phase and wash-out appearance in the portal venous and/or delayed phases.	80%-94%	55%-76%	82%-98%	80%-98%
CT		Diagnostic	Hyperenhancement in the hepatic arterial phase and wash-out appearance in the portal venous and/or delayed phases.	63%-76%	63%-70%	87%-98%	89%-93%	1. Widely available and well validated worldwide. 2. Enables full cross-sectional evaluation of the liver and can provide important staging information. 3. Demonstrates high specificity for HCC diagnosis.	1. Ionizing radiation exposure. 2. Requires application intravenous contrast agents. 3. Less sensitive for early and small lesions.
MRI	All	Diagnostic	Hyperenhancement in the hepatic arterial phase and wash-out appearance in the portal venous and/or delayed phases.	77%-90%	68%-85%	84%-97%	88%-95%	1. No ionizing radiation exposure; 2. Widely available and well validated worldwide; 3. Enables full cross-sectional evaluation of the liver and can provide important staging information; 4. Demonstrate high specificity for HCC diagnosis; 5. Better depiction of tumor intrinsic characteristics than CT.	1. More Sensitive to motion and susceptibility artifact. 2. Requires injection of potentially nephrotoxic contrast agents. 3. More time-consuming than CT or US. 4. Limited sensitivity for early and small lesions.
	Gadolinium-enhanced MRI			67%-82%	57%-75%	68%-95%	86%-94%
	Gadoxetate-enhanced MRI		Arterial phase hyperenhancement, portal venous phase wash-out appearance and hepatobiliary phase hypointensity.	79%-93%	90%-93%	90%-97%	87%-91%	1. Permits evaluation of hepatocyte functions. 2. Very sensitive for early and small lesions. 3. Hepatobiliary phase signal intensity is well correlated with HCC histologic grade. 4. Can help differentiate early HCCs from cirrhosis-associated benign nodules.	1. Prolonged examination time and increased cost. 2. Less available and validated than CT or conventional MR. 3. Some HCCs can appear iso- or even hyperintense on hepatobiliary phase images. 4. Hepatobiliary phase hypointensity may be appreciated in a wide spectrum of diseases with both benign and malignant entities. 5. Delayed phase, which can better depict washout appearance, is absent.

US: Ultrasound; CEUS: Contrast-enhanced ultrasound; CT: Computed tomography; MRI: Magnetic res-onance imaging; HCC: Hepatocellular carcinoma.

Table 2 Comparison of guidelines of different countries and regions

Region	Year	Country/society	Stratification	Cut-off size	AFP	CEUS	EOB-MRI
Asia	2014	Japan/JSH-LCSG	Dynamic pattern	/	Not included	Included	First-line
	2014	Korea/KLCSG-NCC	Size-based	1 cm	Included	Not included	Preferentially recommended
	2014	India/INASL	Size-based	1 cm	Not included	Included	According to availability
	2017	China/NHFPCPRC	Size-based	2 cm	Included	Included	Optional
	2017	APASL	Dynamic pattern	/	Not included	Included	First-line
Europe	2012	EASL-EORTC	Size-based	1 cm/ 2 cm			Not included
America	2011	USA/AASLD	Size-based	1 cm			Not included

AFP: Alpha fetoprotein; CEUS: Contrast-enhanced ultrasonography; EOB-MRI: Gadoxetic acid-enhanced MRI; JSH-LCSG: Japan Society of Hepatology - Liver Cancer Study Group of Japan; KLCSG-NCC: Korean Liver Cancer Study Group - National Cancer Center; INASL: The Indian National Associa-tion for Study of the Liver; NHFPCPRC: National Health and Family Planning Commission of the Peo-ple’s Republic of China; APASL: Asia-Pacific Association for the Study of the Liver; EASL-EORTC: Eu-ropean Association for the Study of the Liver - European Organization for Research & Treatment of Can-cer; AASLD: The American Association for the Study of Liver Diseases.