Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

Table 1 Diagnostic performance of alpha-fetoprotein serum levels in selected studies

Ref.	Year	n	Comparator	Cut-off-level	Sensitivity	Specificity	AUC
Marrero et al[20]	2009	836 total (419 HCC)	Liver cirrhosis	20 ng/mL	59%	90%	0.8
Mao et al[21]	2010	4217 total (789 HCC)	Amongst others healthy controls, HBV carriers, liver cirrhosis	35 ng/mL	58.20%	85.30%
Farinati et al[22]	2006	1158 HCC	No control	400 ng/mL	18%		0.59
Lok et al[23]	2010	39 HCC, 77 matched controls	Hepatitis C	20 ng/mL	61%	81%	0.79

AUC: Area under the cure; HCC: Hepatocellular carcinoma.

Table 2 Diagnostic performance of novel non-invasive biomarkers

Ref.	Year	Marker	n	Comparator	Cut-off-level	Sensitivity	Specifity	AUC
Toyoda et al[31]	2011	hs-AFP-L3%	666	Chronic liver disease and AFP < 20 ng/mL	5%	41.50%	85.10%	0.707
Ertle et al[37]	2013	DCP	586	Chronic liver disease	5 ng/mL	45.80%	95%	0.87
Wan et al[24]	2014	Osteopontin	Meta-analysis (7 studies)	mixed		Pooled: 86%	Pooled: 86%	0.92
Hsia et al[35]	2007	IL-6	128	Mixed, including chronic liver disease and healthy controls	3 pg/mL	46%	95%
Mao et al[21]	2010	GP73	4217	Mixed, including chronic liver disease and healthy controls	8.5 rel. units	74.60%	97.40%	0.94
Giannelli et al[36]	2007	SCCA	961	Liver cirrhosis	3.8 ng/mL	41.90%	82.60%	0.656
Ertle et al[37]	2013	AFP combined with DCP	586	Chronic liver disease	DCP 5 ng/mL AFP 10 ng/mL	78%	89.30%	0.91
Johnson et al[40]	2014	GALAD-score	670	Chronic liver disease		93%	89%

hs-AFP: High-sensitivity α-fetoprotein; DCP: Des-gamma-carboxy-prothrombin; SCCA: Squamous cell carcinoma antigen; GP73: Golgi protein 73; IL-6: Interleukin-6; AUC: Area under the cure.

Table 3 Genetic signatures from tumor tissue and their prognostic significance

Ref.	Year	Correlation with	No. of genes in signature	AUC	P-value
Nault et al[95]	2013	Disease-free survival after resection	5 (tumor)	0.8	< 0.0001
Lim et al[96]	2013	Disease-free survival after resection	25 (tumor)		0.002
Kurokawa et al[97]	2004	Tumor recurrence after resection	20 (tumor)		0.001
Yoshioka et al[98]	2009	Tumor recurrence after resection	172 (tumor)		< 0.0001
Woo et al[99]	2008	Recurrence free survival	628 (tumor)		< 0.01

AUC: Area under the cure.