Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis

Table 1 At risk population for HCC surveillance: AASLD guide lines[21]

Hepatitis B carriers

Asian males 40 years or more

Asian females 50 years or more

All cirrhotic hepatitis B carriers

Family history of HCC

Africans over age 20

For non-cirrhotic hepatitis B carriers not listed above the risk of HCC varies depending on the severity of the underlying liver disease, and current and past hepatic inflammatory activity. Patients with high HBV DNA concentrations and those with ongoing hepatic inflammatory activity remain at risk for HCC

Non-hepatitis B cirrhosis

Hepatitis C

Alcoholic cirrhosis

Genetic hemochromatosis

Primary biliary cirrhosis

Group with lack of evidence. Although the following groups have an increased risk of HCC no recommendations for or against surveillance can be made because a lack of data precludes an assessment of whether surveillance would be beneficial: a1-antitrypsin deficiency, non-alcoholic steatohepatitis, autoimmune hepatitis

Table 2 Overall sensitivity, specificity and predictive value of imaging technique for the diagnosis of hepatocellular carcinoma

Study	Nunber of patients (n)	HCC patients/ HCC instances	Gold standard reference	Imaging technique	Sensitivity (%)	Specificity (%)	PPV (%)	Ref.
Ward et al (2000)	145	25/76	Explant/	MR (SPIO)	66	NA	NA	[72]
			biopsy	MR (Double)	80	NA	93.5
Rode et al (2001)	43	18/13	Explant	SDCT	53.8	92.9	94.3	[58]
				MR (Gd)	76.9	57.1	42.3
Krinsky et al (2001)	71	10/19	Explant	MR (Gd)	53	NA	96.9	[69]
Krinsky et al (2002)	24	24/> 118	Explant	MR (Gd)	33	NA	NA	[70]
De Ledingen et al (2002)	34	21/54	Explant	MDCT	51.9	84.6 pts2	89.5	[55]
				MR (Gd)	61.1	1002	100
Libbrecht et al (2002)	49	17/77	Explant	MDCT	70 pts1	822	NA	[57]
				MR (Gd)	501	792	NA
Zacherl et al (2002)	23	23/50	Explant	MDCT	75	NA	64	[62]
Barthia et al (2003)	31	14/32	Explant	MR (Double)	78	NA	NA	[31]
Burrell et al (2003)	50	29/76	Explant	MDCT	61	NA	87	[3]
				MR (MRA)	76	NA	90
Teefey et al (2003)3	22	9/18	Explant	MDCT	57-67 pts1	69-752	NA	[60]
				MR (Gd)	50-561	63-812	NA
Battakiarjya et al (2004)	30	30/46	Explant	MDCT	67.4	78.9	NA	[53]
				IOCT	68	88.6	NA
Kim et al (2004)	27	27/50	Biopsy/clinical/radiological	MR (Gd)	91.3	NA	92.6	[68]
				MR (SPIO)	77.3	NA	NA
Valls et al (2004)	85	51/85	Explant	MDCT	78.8 pts	NA	88	[61]
Kim et al (2006)	46	31/53	Biopsy/clinical/radiological	MDCT	77.4-79.2	NA	95-97	[56]
				MR (Gd)	92.5-94.3	NA	92-96
Hecht et al (2006)	38	18/19	Explant	MR (Gd)	68.4	65.7	NA	[67]
Ronzoni et al (2007)	88	48/139	Explant	MDCT	64	NA	66.9	[59]
					73.3	NA	79
Lauenstein et al (2007)	115	27/36	Explant	MR (Gd)	77.8	NA	NA	[71]
Forner et al (2008)	89	60/60	Biopsy	MR (Gd)	61.7	96.6	NA	[42]
				CEUS	51.7	93.1	NA
Dai et al (2008)	498	NA/56	Biopsy/	MDCT	80.4	97.9	NA	[52]
			resection	CEUS	91.1	87.2	NA
Choi et al (2008)		47/41	Explant	MDCT	65	NA	NA	[54]
				MR (Gd)	83	NA	NA

¹Patient-based sensitivity;

²Patient-based specificity;

³Two observers; ⁴Three observers. CEUS: Contrast-enhanced ultrasonography; Gd: Gadolinium; HCC Hepatocellular carcinoma; IOCT: Ionized oil computed tomography; MDCT: Multi-detector computed tomography; MR: Magnetic resonance; MRA: Breath-old 3D gadolinium-enhanced angiography; MR (Double): Double-contrast MR with gadolinium and superparamagnetic iron oxide agents; NA: Not applicable; PPV: Positive predictive value; pts: patients; SDCT: Single-detector computed tomography; SPIO: Superparamagnetic iron oxide.

Table 3 Newly found focal liver lesion in patients with cirrhosis. Screening and diagnosis: AASLD guide lines[21]

Focal lesion < 1 cm diameter: screen every 3-4 mo

Focal lesion 1-2 cm diameter: HCC diagnosed when 2 dynamic imaging techniques are concordant for HCC feature

Focal lesion > 2 cm diameter: HCC diagnosed with feature of HCC on 1 dynamic imaging technique

Table 4 Immunohistochemistry for HCC

Marker	Staining pattern	Diagnostic use	Diagnostic value	Ref.
AFP	Specific for HCC Cytoplasm	Expressed in HCC cells cytoplasm but also in: fetal liver, hepatoid tumors, germ cells tumors	Sensitivity 17%-68%	[89-104]
			Specificity 97%
			For HCC
GP-3	Specific for HCC Cytoplasm	Expressed in HCC cell cytoplasm (less so if fibrolamellar or sarcomatoid variants) but also in: fetal liver, hepatoblastoma, melanoma	Sensitivity 49%-91%	[81,109-115]
			Specificity 89%-100%
			For HCC
CD-34	Endothelium	Surface of normal endothelium and HCC trabeculae or acini but also in: myelodysplasia in transformation, GI stromal tumors (high coexpression with bcl-2)	HCC positivity 82%	[117]
p-CEA	Biliary canalicula	Identifies biliary glycoprotein 1 on hepatocyte canalicular pole and cholangiocyte. Useful for differential diagnosis vs cholangiocarcinoma, other adenocarcinoma	HCC positivity 24%-90%	[94,98,100,118-128]
CD-10	Biliary canalicula	Surface of biliary tract cells and in HCC, but also positive in: B cell lymphomas, renal cells carcinoma, melanoma, prostate and pancreas adenocarcinoma. Useful for differential diagnosis vs cholangiocarcinoma, other adenocarcinomas	HCC positivity 28%-86%	[94,98,100,119,120,122-124,126,128]
Ki67 HepPar1	Cell proliferation marker HCC & normal Hepatocyte citoplasm	Assessing cell proliferation rate, correlates with tumor grade and clinical course. Useful to differentiate between HCC and hepatic adenoma	HCC positivity rate 10%-50%	[129]
		Expressed in HCC and in normal liver cells, but also in hepatoblastoma. useful for differential diagnosis vs cholangiocarcinoma and metastases	HCC positivity 66%-100%	[130-136]
Cytokeratins	Epithelial cells	Useful for differential diagnosis vs cholangiocarcinoma. HCC profile: CK7/CK19/CK8/CK18 = - / - / + / +	HCC positivity 76%-96%	[97,101,104,137-140]