Guide for diagnosis and treatment of hepatocellular carcinoma

Table 1 Sensitivity and specificity of different radiological modalities in hepatocellular carcinoma

	Sensitivity (%)	Specificity (%)
US	60	97
Colour Doppler US	92	100
MPCT	68	93
MRI	81	85
Angiography	82-93	73

MPCT: Multiphasic helical computed tomography; MRI: Magnetic resonance imaging; US: Ultrasound.

Table 2 Currently used and investigational serum tumour markers[101]

Markers	Character	Cut-off level	Sensitivity	Specificity	Comments
AFP	Oncofoetal glycoprotein	10-16 ng/dL	60%-80%	70%-90%	Poor marker alone
		20 ng/dL	39%-66%	76%-97%
AFP-L3	AFP variant (subtype)	10%	39.9%	93.4%	Useful in combination
		15%	36.1%-96%	92%-99.5%	with other markers
GP73	Golgi-specific membrane protein	10 relative units	69%	86%	Promising marker
GPC3	Oncofoetal glycoprotein	2 ng/dL	51%	90%	Limited utility as a marker
DCP	Abnormal prothrombin	40 mAU/mL	48%-62%	81%-98%	Useful in combination
HS-GGT	Abnormal prothrombin	5.5 IU/mL	43.8%-74%	Not available	Non specific
AFU	Lysosomal enzyme	870 nmol/mL per hour	82%	71%	Lower specificity and poor marker

AFP: Alpha-fetoprotein; AFP-L3: Lens culinaris-reactive AFP; GP73: Golgi protein 73; GPC3: Glypican-3; DCP: Des-gamma-carboxyprothrombin; GGT: Gamma-glutamyl transferase; AFU: Alpha-L-fucosidase.

Table 3 MicroRNAs with potential prognostic impact in patients with hepatocellular carcinoma

MiRNAs	Molecular alteration	Clinical significance	Ref.
20 miRNAs	Signature	Venous metastasis, overall survival	[154]
19 mi NAs	Signature	Poor survival	[155]
MiR-19a, miR-886-5p, miR-126, miR-233, miR-24, and miR-147	Signature	Predictor of overall survival and recurrence-free survival after LT	[156]
MiR-26a	Down-regulation	Poor survival	[157]
MiR-122	Down-regulation	Gain of metastasis properties	[158,159]
MiR-122	Down-regulation	Early recurrence	[160]
Let-7 members	Down-regulation	Early recurrence	[161]
MiR-199a-3p	Down-regulation	Reduced time to recurrence	[162]
MiR-199b-5p	Down-regulation	Poor overall survival and progression-free survival rates	[163]
MiR-101	Down-regulation	Advanced tumour progression, poor prognosis	[164]
MiR-125a	Up-regulation	Better survival	[165]
MiR-92, miR-20, miR-18	Up-regulation	Poor differentiation	[166]
MiR-372	Up-regulation	Advanced TNM stage	[167]
MiR-221	Up-regulation	Multi-nodularity, reduced time to recurrence	[168]
MiR-221	Up-regulation	Gain of metastatic properties	[169]
MiR-221	Up-regulation	High tumour capsular infiltration	[170]
MiR-17-5p	Up-regulation	Multiple tumour nodules, vein invasion, shortened overall survival	[171]
MiR-155	Up-regulation	High recurrence and poor prognosis following OLT	[172]
MiR-203	Up-regulation	Good prognosis	[173]
MiR-18	Up-regulation	Poor prognosis	[174]

Data adapted from Negrini et al[175]. MiRNAs: MicroRNAs; TNM: Tumour-node-metastasis; LT: Liver transplantation; OLT: Orthotopic liver transplantation.

Table 4 Ongoing randomised phase II-III trials aimed at changing the standard of care in hepatocellular carcinoma management during the period 2012-2013[10]

Indication	Randomised studies
Adjuvant	Sorafenib vs placebo
Intermediate HCC	Chemoembolisation ± sorafenib
	Chemoembolisation ± brivanib
	Chemoembolisation ± everolimus
Advanced HCC
First line	Sorafenib ± erlotinib
	Sorafenib vs brivanib
	Sorafenib vs sunitinib
	Sorafenib vs linifanib
	Sorafenib ± yttrium-90
	Sorafenib ± doxorubicin
Second line	Brivanib vs placebo
	Everolimus vs placebo
	Ramucirmab vs placebo

HCC: Hepatocellular carcinoma.