Surveillance and diagnosis of hepatocellular carcinoma: A systematic review

Table 1 Studies about the advantages and results of surveillance in HCC

Ref.	Location	Inclusion period	n	Screening (%)	Results surveillance group
	UNI/MULTI
Edenvik et al[21]	Sweden UNI	2005-2012	616	22%	Better survival
van Meer et al[22]	Netherlands MULTI	2005-2012	1074	27%	Smaller tumor size, earlier tumor stage, more often curative treatment and improving 1, 3, 5 years survival rates
Singal et al[23]	United States MULTI	2012-2013	374	42%	Early tumor detection and improved survival
Mittal et al[24]	United States MULTI	2005-2010	887	46.5%	Reduction in mortality
Atiq et al[25]	United States UNI	2010-2013	680	11.5%	Early HCC

UNI: Uni-center; MULTI: Multicenter; HCC: Hepatocellular carcinoma.

Table 2 Annual incidence of HCC in cirrhotic patients by etiology

Ref.	Location	n	Follow-up period	Study design	Incidence
	UNI/MULTI
Tansel et al[42]	North America, Europe, Asia, Australia. MULTI	6528	Median 8 yr	Meta-analysis	1.007% (95%CI: 0.69–1.47)
Fattovich et al[43]	Europe MULTI	297	Median 66 yr	Retrospective	2.2% for hepatitis B virus and 2.5% for hepatitis C virus
Mancebo et al[44]	Spain UNI	450	Median 42 mo	Prospective	2.6%
Shibuya et al[45]	Japan MULTI	396 (134 stage III or IV)	Median 43 mo	Prospective	1.5% for PBC stage III/IV

UNI: Uni-center; MULTI: Multicenter.

Table 3 Annual HCC incidence in cirrhotic patients with HCV

Ref.	Location	n	Follow-up period	Study design	Incidence
	UNI/MULTI
Li et al[55]	US MULTI	17836	Median 2719.2 d in patients treated with IFN, and 396.4 d for the ones treated with DAAs	Retrospective	Annual incidence in cirrhotic patients 2.28% treated with DAA and 2.12% in patients treated with IFN. Annual incidence in patients with no treatment of 4.531%
Piñero et al[57]	Latin America MULTI	1400	Median 16 mo	Prospective	Accumulated incidence in cirrhotic patients of 3% at 1 year and 6% at 2 yr
Waziry et al[59]	Europe, Asia, North America, South America MULTI	11523	Median 5.5 yr in patients treated with IFN and 1 yr in patients treated with DAA	Meta-analysis	Annual incidence 1.14% in patients with SVR treated with IFN and 2.96% in patients SVR treated with DAA. After adjusting for age and follow-up period, no greater risk is observed in those treated with DAA
Nahon et al[63]	France Multi	1270	Median 67.5 mo	Prospective	2.6% in cirrhotic patients in SVR with DAA. In patients with SVR the annual incidence is 12%

UNI: Uni-center; MULTI: Multicenter; IFN: Interferon; DAA: Direct-acting antiviral; SVR: Sustained viral response.

Table 4 Findings for HCC diagnosis

Vascular phase (CT/MRI)	Feature	Comments
Late arterial phase	Arterial phase hyperenhancement also known as "wash-in"	The lesion must be hypervascular with an enhancing part higher in attenuation or intensity than the liver, depicting a nonrim-like enhancement unequivocally greater in whole or in part of the lesion than the surrounding liver parenchyma
Portal phase or late venous phase	Washout	The lesion will present lower contrast uptake than the surrounding parenchyma
	"Capsule appearance"	A ring of peripheral uptake in the lesion

CT: Computed tomography; MRI: Magnetic resonance imaging.

Table 5 Computed tomography/magnetic resonance imaging diagnostic table

	Nonrim-like APHE
Observation size	10-19 mm	≥ 20 mm
Enhancing "capsule"	LR-4	LR-5
Non-peripheral washout or threshold grown	LR-5	LR-5

APHE: Arterial phase hyperenhancement; LR-5: LI-RADS lesions.

Table 6 Ancillary findings (LIRADS 2018)

Favoring HCC in particular	Favoring malignancy in general	Favoring benignity
Non-enhancing "capsule"	US visibility as discrete nodule	Size stability > 2 yr
Nodule-in-nodule	Subthreshold growth	Size reduction
Mosaic architecture	Restricted diffusion	Parallels blood pool
Blood products in mass	Mild-moderate T2 hyperintensity	Marked T2 hyperintensity
Fat in mass, more than adjacent liver	Fat sparing in solid mass	Undistorted vessels
	Iron sparing in solid mass	Iron in mass, more than liver
	Transitional phase hypointensity	Hepatobiliary phase isointensity
	Hepatobiliary phase hypointensity
	Corona enhancement

HCC: Hepatocellular carcinoma; US: Ultrasonography.

Table 7 LI-RADS 2018 recommendations for untreated ≥ 1 cm lesions without pathologic proof in patients at high risk for HCC

LR-NC	Cannot be categorized (image degradation, lack of key phases)
LR-1	Definitely benign (e.g., cyst, hemangioma, perfusion alteration)
LR-2	Probably benign (probable but no definitive LR-1 findings)
LR-3	Intermediate probability of malignancy (nonmalignant and malignant entities each have moderate probability)
LR-4	High probability but no certainty of HCC
LR-5	Definitively HCC
LR-M	Probably or definitely malignant, not HCC specific (e.g., HCC not meeting LR-5 criteria, intrahepatic cholangiocarcinoma, metastases to liver)
LR-TIV	Tumor in vein

HCC: Hepatocellular carcinoma.