Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Table 1 Hepatocellular carcinoma scores and staging systems published in the recent years

Scores and classifications	Liver function	AFP	PS	Tumor spread
Okuda 1985	Ascites, albumin, bilirubin	No	No	Hepatic spread 50% < vs > 50%
CLIP 1998	Child-Pugh score	< 400 ng/mL vs≥ 400 ng/mL	No	Nodule(s), hepatic spread 50% ≤vs > 50%
				Portal vein thrombosis
GRETCH 1999	Bilirubine, phosphatases alcalines	< 35 ng/mL vs≥ 35 ng/mL	Yes	Portal vein thrombosis
BCLC 1999	Child-Pugh score	No	Yes	Nodule(s), size
				Portal vein thrombosis
c-JIS 2003	Child-Pugh score	No	No	TNM LCSGJ
bm-JIS 2008	Child-Pugh score	Yes (+ AFP-L3 + DCP)	No	TNM LCSGJ
TIS 2010	Child-Pugh score	< 400 g/mL ≥ 400 ng/mL	No	Total tumor volume
HKLC 2014	Child-Pugh score	No	Yes	Nodule(s), size
				Portal vein thrombosis

BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program; JIS: Japan Integrated Staging; HKLC: Hong Kong Liver Cancer; TIS: Taipei Integrated Scoring System; AFP: Alpha-fetoprotein; PS: Performance Status; bm-JIS: Biomarker combined JIS; DCP: Des-gamma-carboxy prothrombin; LCSGJ: Liver Cancer Study Group of Japan; TNM: Tumor-node-metastasis.

Table 2 Definitions of the Okuda score and the Cancer of the Liver Italian Program score

Okuda score			CLIP score
Parameters	(+) 1 point	(-) 0 point	0 point	1 point	2 points
Tumor spread	> 50%	< 50%
Albumin, g/dL	< 3	> 3
Bilirubin, mg/dL	> 3	< 3
Ascites	Yes	No
Child-Pugh score			A	B	C
Tumor spread			Unipolar and hepatic spread ≤ 50%	Multinodular and hepatic spread ≤ 50%	Massive or hepatic spread > 50%
Portal vein thrombosis			No	Yes
AFP, ng/dL			< 400	≥ 400

AFP: Alpha-fetoprotein; CLIP: Cancer of the Liver Italian Program.

Table 3 Definitions of the c-Japan Integrated Staging score and the biomarker combined Japan Integrated Staging score

	0 point	1 point	2 points	3 points
Score c-JIS
Child-Pugh stage	A	B	C
TNM stage by LCSGJ1	I	II	III	IV
Score bm-JIS
Child-Pugh stage	A	B	C
TNM stage by LCSGJ1	I	II	III	IV
Elevated tumor markers, n (AFP, AFP-L3, DCP)	0	1	2 or 3

¹Definitions of the TNM stage by the LCSGJ; Stage I: T1 (fulfilling 3 T factors) N0 M0; Stage II: T2 (fulfilling 2 T factors) N0 M0; Stage III: T3 (fulfilling 1 T factor) N0 M0; Stage IV: T4 (fulfilling 0 T factor) N0 M0 or any T N0 - 1 M1; T factor: (1) single; (2) < 2 cm; and (3) no vascular involvement. LCSGJ: Liver Cancer Study Group of Japan; bm-JIS: Biomarker combined-Japan Integrated Staging.

Table 4 Barcelona Clinic Liver Cancer C hepatocellular carcinoma, a broad spectrum of tumors; example of the Advanced Liver Cancer Prognostic System score[36]

Parameters	Points
Ascites	2
Abdominal pain	2
Weight loss	2
Child-Pugh grade A/B/C	0/2/5
alkaline phosphatase, UI/L > 200	3
Bilirubin, mcmol/L ≤ 33/> 33- ≤ 50/> 50	0/1/3
Urea, mmol/L > 8.9	2
Portal vein thrombosis	3
Tumor size: Diffuse/> 5 cm/ ≤ 5 cm	4/3/0
Lung metastases	3
AFP, ng/mL > 400	4
Probability of patients surviving at least 3 mo estimated by the ALCPS score[36]
Score ≤ 8 points: 82.0% (95%CI: 76.5%-87.5%)
Score 9-15 points: 53.4% (95%CI: 48.3%-57.7%)
Score ≥ 16 points: 18.9% (95%CI: 14.7%-23.3%)

Probability of patients surviving at least 3 mo estimated by the ALCPS score[36]. AFP: Alpha-fetoprotein; ALCPS: Advanced Liver Cancer Prognostic System.

Table 5 NIACE score[38]

Score NIACE	Points
Nodules < 3	0
Nodules ≥ 3	1
Infiltrative HCC: No	0
Infiltrative HCC: Yes	1.5
AFP < 200 ng/mL (at baseline)	0
AFP ≥ 200 ng/mL (at baseline)	1.5
Child-Pugh grade A	0
Child-Pugh grade B	1.5
ECOG PS 0	0
ECOG PS ≥ 1	1.5

AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; ECOG (PS): Eastern Cooperative Oncology Group (Performance Status).

Table 6 Comparison of prognostic performance of the NIACE, Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems[44]

Score	Discriminatory ability linear trend test		Homogeneity likelihood ratio test		Akaike information criterion	C-index (95%CI)
	LT (χ2)	P value	LR (χ2)	P value
NIACE	91.6906	< 0.0001	532.0369	< 0.0001	10648.198	0.718 (0.688-0.748)
BCLC	79.0342	< 0.0001	380.4100	< 0.0001	10805.825	0.674 (0.645-0.704)
HKLC	71.8861	< 0.0001	455.3169	< 0.0001	10740.918	0.698 (0.673-0.731)
CLIP	87.2785	< 0.0001	430.3872	< 0.0001	10749.848	0.716 (0.687-0.746)

BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program; HKLC: Hong Kong Liver Cancer; LR: Likelihood ratio; LT: χ² linear trend test.

Table 7 Prognostic scores before the first transarterial chemoembolization

HAP (0 to 4 points)		NIACE (0 to 7 points)		STATE
Before the first TACE
Albumin < 36 g/dL	1 point	≥ 3 nodules	1 point	Albumin (g/L)
Bilirubin > 17 mcmol/L	1 point	infiltrative HCC vs nodular HCC	1.5 points	-12 (tumour load exceeding the up-to-7 criteria)
			0
AFP > 400 ng/mL	1 point	AFP ≥ 200 ng/mL	1.5 points
		Child-Pugh A vs Child-Pugh B	0
			1.5 points
Size of dominant tumour > 70 mm	1 point	ECOG PS ≥ 1	1.5 points	-12 (if CRP ≥ 1 mg/dL)
No chemoembolization
≥ 2 points		> 3 points		< 18 points

HAP: Hepatoma arterial-embolisation prognostic; AFP: Alpha-fetoprotein; TACE: Transarterial chemoembolization; HCC: Hepatocellular carcinoma; ECOG: Eastern Cooperative Oncology Group; PS: Performance status; CRP: C reactive protein; STATE: Selection for transarterial chemoembolisation treatment.

Table 8 Pronostic scores before retreatment with transarterial chemoembolization

ART (0 to 8 points)		ABCR (-3 to 6 points)
Before the second, the third TACE…..
No radiological response	1 point	AFP < 200 ng/mL	0
		AFP ≥ 200 ng/mL	1 point
AST increased > 25%	4 points	BCLC A/B/C	0/2/3 points
Child-Pugh increased: 1 point	1.5 points	Child-Pugh increased ≥ 2 points	2 points
Increased: ≥ 2 points	3 points	Radiological response	-3 points
No chemoembolization
ART ≥ 2.5 points		ABCR > 2 points

TACE: Transarterial chemoembolization; ART: Assessment for retreatment with TACE; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer.