Comparison between hepatocellular carcinoma prognostic scores: A 10-year single-center experience and brief review of the current literature

Table 1 Description of main features of prognostic score systems for hepatocellular carcinoma

Score system	Parameters taken into account	Classes/ levels	1-, 2-, 3-, or 5-yr survival rates/median survival	Ref.
BCLC	Tumor size; presence of metastasis; portal hypertension; Child Pugh score; total bilirubin; performance status	Stage 0 (very early HCC); stage A (early HCC, subdivided into A1-A4); stage B (Intermediate HCC); stage C (advanced HCC); stage D (end-stage HCC)	5-yr survival rates: 50%-70% for BCLC 0-A;2-yr survival rates: 63% for BCLC B; 1-yr survival rates: 82%, 44% and 11% for BCLC B, C and D respectively	Llovet et al[34], Mazzaferro et al[35], Weinmann et al[36], Barman et al[37], Yopp et al[38]
Okuda staging system	Tumor size (tumor > 50% of the liver; presence of ascites; albumin < 3 g/dL; bilirubin > 3 mg/dL	Stage I (0 factors); stage II (1-2 factors); stage 3 (3-4 factors)	1-yr survival rates: 57% for stage 1, 20% for stage 2 and 3% for stage 3 respectively	Maida et al[18]
CLIP staging system	Tumor size; tumor morphology (uninodular, < 50%; multinodular, < 50%; massive or > 50%); Child-Turcotte-Pugh score; alpha-fetoprotein levels (< or ≥ 400 ng/mL); presence of portal vein thrombosis	One point each parameter (total score ranging from 0 to 6)	1-yr survival rates: 86% for CLIP 0, 76% for CLIP 1, 57% for CLIP 2, 38% for CLIP 3, 22% for CLIP 4, 9% for CLIP 5 and 0% for CLIP 6 respectively; 2-yr survival rates: 69% for CLIP 0, 53% for CLIP 1, 25% for CLIP 2, 7% for CLIP 3, 10% for CLIP 4 respectively; 3-yr survival rates: 58% for CLIP 0, 39% for CLIP 1, 15% for CLIP 2, 6% for CLIP 3, 5% for CLIP 4	[19]
GRETCH staging system	Serum bilirubin; alkaline phosphatase; alpha-fetoprotein; evidence of portal obstruction; Karnofsky score	Stage A (low risk); stage B (intermediate risk); stage C (high risk)	1-yr survival rates are 79%, 31% and 4% for stage A, B and C, respectively	Maida et al[18], Cammà et al[20]
Japanese integrated staging score	LCSGJ TNM (presence of single mass; dimension < 2 cm absence of vessel invasion); Child-Pugh score	Total JIS score is the sum of LCSGJ TNM (I to IV are assigned 0 to 3 points) and Child Turcotte-Pugh score (A, B or C are assigned 0, 1 or 2 points)	2-yr survival rates are 94.5%, 88.9% 78.2%, 52.7%, 30.3% and 15.3% for JIS 0 to JIS 5	Kudo et al[21]
Tokyo scoring system	Serum albumin; serum bilirubin; tumor size; number of nodules, each of which is attributed a score	Total Tokyo score is the sum of: 0 points for serum albumin levels > 3.5 g/dL, serum bilirubin levels < 1 mg/dL, tumor size < 2 cm and ≤ 3 tumors; 1 point for serum albumin levels 2.8-3.5 g/dL, serum; bilirubin levels 1-2 mg/dL and tumor size 2-5 cm; 2 points for serum albumin levels < 2.8 g/dL, serum; bilirubin levels > 2 mg/dL, tumor size > 5 cm and > 3 tumors.	1-yr survival rates: 100% for score 0, 97.6% for score 1, 94.2% for score 2, 84.6% for score 3, 73.8% for score 4-6; 2-yr survival rates: 98.1% for score 0, 90.5% for score 1, 81.7% for score 2, 70.5% for score 3, 52.4% for score 4-6; 3-yr survival rates: 96.2% for score 0, 90.5% for score 1, 63.5% for score 2, 47.4% for score 3, 33.3 % for score 4-6; 5-yr survival rates: 52.8% for score 0, 37.3% for score 1, 27.9% for score 2, 19.2% for score 3, 16.7 % for score 4-6	Tateishi et al[54]
MESIAH staging score	Tumor size; number of nodules; vascular invasion; extrahepatic metastasis; age; serum albumin; AFP levels; MELD score	Each of the parameters is assigned a specific coefficient.	Along with the score is provided a tailored probability of survival at 1, 3, 6, 12, 24 and 36 mo	Kinoshita et al[24], Choi et al[25]
ALBI grading system	Serum bilirubin (µmol/L); serum albumin (g/L).	ALBI grade 1 corresponds to a score ≤ -2.60.ALBI grade 2 corresponds to a score > -2.60 and ≤ -1.39.ALBI grade 3 corresponds to a score > -1.39.	In European patients, the median survivals reported in the study were 24.7 mo for ALBI grade 1, 11.4 mo for ALBI grade 2 and 4.9 mo for ALBI grade 3.	Ogasawara et al[26]
ALBI-based BCLC staging system	The procedure to calculate the BCLC stage stays the same, but, instead of Child-Turcotte-Pugh grade A, B and C, ALBI grade 1, 2 and 3 are employed respectively.	An ALBI score 1 can be present in BCLC stage 0, A, B and C; ALBI score 2 can be present in BCLC stage A, B and C; ALBI score 3 is related to BCLC stage D	1-yr survival rates: 91.3% for ALBI- based BCLC 0, 85.8% for ALBI- based BCLC stage A, 72.6% for ALBI- based BCLC stage B, 32.9% for ALBI- based BCLC Stage C, 26.6% for ALBI- based BCLC stage D. 2-yr survival rates: 79.7% for ALBI- based BCLC 0, 69.2% for ALBI- based BCLC stage A, 46% for ALBI- based BCLC stage B, 14.5% for ALBI- based BCLC Stage C, 15.1% for ALBI- based BCLC stage D. 3-yr survival rates: 71.5% for ALBI- based BCLC 0, 69.2% for ALBI- based BCLC stage A, 26.4% for ALBI- based BCLC stage B, 7.2% for ALBI- based BCLC Stage C, 15.1% for ALBI- based BCLC stage D. 5-yr survival rates: 50% for ALBI- based BCLC 0, 30.1% for ALBI- based BCLC stage A, 10.2% for ALBI- based BCLC stage B, 2.9% for ALBI- based BCLC Stage C, 2% for ALBI- based BCLC stage D.	Chan et al[45]
ALBI-T score	ALBI grade; LCSGJ TNM staging system	The final score, ranging from 0 to 5, is obtained by adding the ALBI grade to the TNM stage and then subtracting 2	The reported median survival were 137.7 mo for ALBI-T score 0, 83.2 mo for ALBI-T score 1, 53.4 mo for ALBI-T score 2, 27.4 mo for ALBI-T score 3, 5 mo for ALBI-T score 4 and 1.4 mo for ALBI-T score 5	Hiraoka et al[27]
MESH scoring system	Tumor burden (within/beyond Milan criteria); vascular invasion; metastasis; Child-Pugh score; Performance Status; serum AFP; ALP	The sum of the points obtained in the various sections leads to the final MESH score (ranging from 0 to 6).	1-yr survival rates: 89.5% for MESH 0, 82.5% for MESH 1, 74% for MESH 2, 45.2% for MESH 3, 21.4% for MESH 4, 5.7% for MESH 5, 0% for MESH 6; 2-yr survival rates: 72.9% for MESH 0, 52.8% for MESH 1, 74% for MESH 2, 49.4% for MESH 3, 12.8% for MESH 4, 3.7% for MESH 5; 3-yr survival rates: 53.3% for MESH 0, 52.8% for MESH 1, 36% for MESH 2, 14.8% for MESH 3, 8.2% for MESH 4, 1.4% for MESH 5; 5-yr survival rates: 38.6% for MESH 0, 28% for MESH 1, 14.9% for MESH 2, 5.1% for MESH 3, 3.5% for MESH 4, 0% for MESH 5	Liu et al[28]
NIACE score system	Number of nodules (N); infiltrative HCC (I); serum AFP levels (A); Child-Turcotte-Pugh grade (C); ECOG PS (E)	The sum of the points obtained in the various sections leads to the final NIACE score (ranging from 0 to 7).	The reported median survivals are 44 mo for NIACE 0, 22 mo for NIACE 1, 20 mo for NIACE 1.5, 14 mo for NIACE 2.5, 9 mo for NIACE 3, 7 mo for NIACE 4, 4 mo for NIACE 4.5, 4 mo for NIACE 5.5, 3 mo for NIACE 6 and 3 mo for NIACE 7	Adhoute et al[29]
ITA.LI.CA score system	Tumor burden (assessed via the ITA.LI.CA tumor staging); performance status test; Child-Pugh score; AFP concentration	Each is assigned an amount of points that finally contribute to the total prognostic score (from 0, best prognosis, to 13, worst prognosis)	The median survival was reported to be 61 mo for patients in quartile 1 (ITA.LI.CA score ≤ 1), 38 mo for patients in quartile 2 (ITA.LI.CA score 2-3), 23 mo for patients in quartile 3 (ITA.LI.CA score 4-5) and 8 mo for patients in quartile 4 (ITA.LI.CA score > 5)	Farinati et al[46], Yoo et al[47], Borzio et al[48]
NSP scoring system	Tumor number (N); tumor size (S); prothrombin time (P)	The sum of the points obtained in the various sections leads to the final NSP score. Using a threshold score of 1 allows to identify 2 subgroups with different prognosis	1-yr survival rates are 88.4% for NSP ≤ 1 and 62.7% for NSP > 1; 3-yr survival rates are 57% for NSP ≤ 1 and 16.9% for NSP > 1; 5-yr survival rates are 30.2% for NSP ≤ 1 and 20.4% for NSP > 1	Zhang et al[30]
HAP scoring system	Serum levels of albumin; serum AFP; bilirubin; maximum tumor diameter; 1 point is assigned for serum albumin levels < 3.6 g/dL, serum AFP > 400 ng/dL, serum bilirubin > 0.99 mg/dL (17 mmol/L) and for a maximum tumor diameter > 7 cm	HAP A (low risk) for a total score 0, -HAP B (intermediate risk) for a total score 1; HAP C (high risk) for a total score 2; HAP D (very high risk) for a total score > 2	1-yr survival rates: 64.7% for HAP A, 50% for HAP B, 38.5% for HAP C, 25% for HAP D; 2-yr survival rates: 17.6% for HAP A. 10.3% for HAP B, 10.3% for HAP C, 10% for HAP D	Kadalayil et al[31]
STATE scoring system and START strategy	Up-to-7 criteria; serum albumin level; C reactive protein values. A neoplasia within Up-to-7 criteria is assigned 0 points, while a neoplasia beyond the criteria subtracts 12 points.C reactive protein values < 1 mg/dL are attributed 0 points, whereas values ≥ 1 mg/dL subtract 12 points	2 groups of patients presenting different prognosis were identified: STATE score < 18 and ≥ 18	Median survival of 20.5 mo for patients with a STATE score ≥ 18. Median survival of 6.1 mo for patients with a score < 18	Hucke et al[32]
SNACOR staging system	Tumor size (S); tumor number (N); baseline AFP (A); Child-Turcotte-Pugh class (C); objective radiological response (OR). No points are assigned for tumors < 5 cm, a number of tumors < 4, a baseline AFP < 400 ng/mL, a Child-Turcotte-Pugh class A and for complete response or partial response after TACE. 1 point is assigned for tumors ≥ 5 cm and for a Child-Turcotte-Pugh class B; 2 points are assigned for a number of tumors ≥ 4; 3 points are assigned for a baseline AFP ≥ 400 ng/ml and for stable disease or progressive disease after TACE	The final SNACOR score is the sum of the points obtained for the previous features and ranges from 0 to 10	1-yr survival rates: 80.9% for SNACOR 0-2, 69.4% for SNACOR 3-6, 40% for SNACOR 7-10; 2-yr survival rates: 55.3% for SNACOR 0-2, 38.9% for SNACOR 3-6, 20% for SNACOR 7-10; 3-yr survival rates: 42.6% for SNACOR 0-2, 26.4% for SNACOR 3-6, 6.7% for SNACOR 7-10; 5-yr survival rates: 24.5% for SNACOR 0-2, 16%% for SNACOR 3-6, 3.3% for SNACOR 7-10	Mähringer-Kunz et al[33]

AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin; BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program; ECGO: Eastern Cooperative Oncology Group; GRETCH: Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire; HAP: Hepatoma arterial-embolization; HCC: Hepatocellular carcinoma; HKLC: Hong Kong Liver Cancer; ITA.LI.CA: Italian Liver Cancer; JIS: Japanese Integrated Staging; LCSGJ: Liver Cancer Study Group of Japan; MELD: Model for End-Stage Liver Disease; MESH: Model to estimate survival for hepatocellular carcinoma patients; MESIAH: Model to Estimate Survival in Ambulatory hepatocellular carcinoma patients; NSP: Needle and syringe programmes; SNACOR: Tumour size and number, baseline alpha-fetoprotein, Child-Pugh and objective radiological response; STATE: Selection for Transarterial chemoembolization Treatment; TACE: Transarterial chemoembolization; TNM: Tumor-node-metastasis.

Table 2 Demographic and biochemical factors, liver function, features of hepatocellular carcinoma nodules, treatments and prognosis of our study cohort

Feature of interest	Study population, n = 140	Intergroup statistical significance
Gender
Male	109 (77.9%)
Female	31 (22.1%)
Age at diagnosis, yr	71.6 (65.6; 75.6)
Liver disease etiology
Viral	36 (25.7%)
Alcoholic	30 (21.4%)
Metabolic	19 (13.6%)
Mixed	55 (39.3%)
Laboratory parameters at diagnosis
Albumin, g/dL	1.12 (0.94-2.23)
INR	1.12 (0.94-2.23)
Total bilirubin, mg/dL	1.06 (0.37-14.47)
AST, UI/L	41 (11-511)
ALT, UI/L	32 (7-336)
ALP, UI/L	99 (40-529)
GGT, UI/L	69 (11-473)
Total serum proteins, g/dL	7.3 (5.1-8.9)
AFP, ng/mL	9.3 (5-110)
Creatinine, mg/dL	0.89 (0.5-2.99)
White blood cells, × 103 cells/µL	5.04 (1.51-12.18)
Red blood cells, × 106 cells/µL	4.34 (2.85-6.78)
Hemoglobin, g/dL	13.5 (8.7-17.8)
Platelets, × 103platelets/µL	113 (29-346)
Sodium, mmol/L	139 (128-145)
Potassium, mmol/L	4.24 (3.40-6.15)
Clinical characteristics at diagnosis
Ascites	11 (7.9%)
Portal hypertension	64 (45.7%)
Hepatic encephalopathy	10 (7.1%)
Portal vein thrombosis	10 (7.1%)
Metastasis	2 (2.4%)
Child-Turcotte-Pugh
Class A	116 (82.9%)
Class B	22 (15.7%)
Class C	2 (1.4%)
MELD score	9 (6-25)
Karnofsky score
100	136 (97.1%)
90	3 (2.1%)
80	0 (0%)
70	1 (0.7%)
< 70	0 (0%)
ECOG PS
0	137 (97.9%)
1	3 (2.1%)
> 1	0 (0%)
Number of nodules at diagnosis
1	91 (65%)
2	31 (22.1%)
3	7 (5%)
4	5 (3.6%)
5	6 (4.3%)
Nodule dimensions
Nodule diameter, mm	30 (20; 40)
Total tumor volume, cm3	14.13 (5.45-36.43)
Milan criteria
Within	99 (71.2%)
Beyond	40 (28.8%)
Up-to-7 criteria
Within	113 (81.3%)
Beyond	26 (18.7%)
Treatment
Type
Surgical resection	28 (20%)
Local ablation	49 (35%)
TACE	54 (38.6%)
Sorafenib	2 (1.4%)
Support	7 (5%)
Number
< 2	63 (45%)
≥ 2	77 (55%)
Response at 1 mo after treatment
Complete response	72 (51.4%)
Of whom treated with curative treatment	56 (77.7%)
Partial response	40 (28.6%)
Of whom treated with curative treatment	17 (42.5%)
Stable disease	14 (10%)
Of whom treated with curative treatment	1 (7.1%)
Disease progression	10 (10%)
Of whom treated with curative treatment	1 (10%)
Ultrasound surveillance every 6 mo
Adhesion to ultrasound surveillance
Under surveillance	81 (57.9%)
Not under surveillance	59 (42.1%)
Nodule diameter, mm		P < 0.001
Under surveillance	25 (20; 35)
Not under surveillance	34 (25; 45)
Number of nodules at diagnosis		P < 0.001
Under surveillance, < 2 nodules	69 (85.2%)
Not under surveillance, < 2 nodules	22 (37.3%)
Choice of curative treatment		P = 0.037
Under surveillance	54 (66.6%)
Not under surveillance	29 (49.2%)
Survival time, mo
Overall survival	35 (17;67)
Survival related to gender		NS
Male	34 (20; 80)
Female	35 (16; 64)
Survival related to etiology		NS
Viral	32 (15; 65)
Non-viral	41 (19; 67)
Survival related to treatment choice		P = 0.013
Curative (surgery/ablation)	48 (18; 68)
Non-curative (TACE/sorafenib/support)	23 (14; 34)
Survival related to ultrasound surveillance		P = 0.002
Under surveillance	48 (20; 75)
Not under surveillance	30 (12; 49)
Survival related to AFP		P < 0.001
AFP ≤ 200 ng/mL	55 (34; 75)
AFP > 200 ng/mL	22 (12; 54)

AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ECGO: Eastern Cooperative Oncology Group; GGT: Gamma glutaryl transferase; INR: International normalized ratio; MELD: Model for End-Stage Liver Disease; TACE: Transarterial chemoembolization.

Table 3 Patients’ allocation and their median survival according to prognostic scores taken into account

Score	Number of patients	Percentage	Median survival in mo	Statistical significance for prognostic stratification	Median survival in the original study in mo
ITA.LI.CA				P < 0.001
0	7	5%	93.5
1	33	23.6%	57.9
2	19	13.6%	63.1
3	38	27.1%	40.6
4	20	14.3%	25.2
5	11	7.8%	21.1
6	5	3.6%	20.8
7	4	2.9%	10.3
8	3	2.1%	4.3
> 8	0	0%
ITA.LI.CA
0-1	40	28.6%	57.9		57-61
2-3	57	40.7%	43		43-48
4-5	31	22.1%	21.7		23
> 5	12	8.6%	10.4		9-8
BCLC				P = 0.001
0	15	10.7%	> 81.1		> 60
A	83	59.3%	44.9		> 60
B	38	27.1%	21.3		20
C	2	1.4%	3.1		11
D	0	0%			< 3
BCLC A				P = 0.022
A1	29	20.7%	61.9		43.4
A2	25	17.6%	44.3		28.9
A3	5	3.5%	10.7		25.4
A4	24	17.1%	34.4		22.3
BCLC B (Bolondi)				P = 0.007
B1	13	9.3%	34.7		31.9
B2	19	15.7%	25.2		26.9
B3	3	0.7%	10.4		13.5
B4	3	1.4%	7.8		10.9
CLIP				P = 0.001	32
0	59	42.1%	50.7		27
1	47	33.6%	53.3		15
2	19	13.6%	20.5		9
3	12	8.6%	17.8		7
4	3	2.1%	3.1		5
> 4	0	0%			3
JIS				P = 0.049
0	27	19.3%	70.8		22.6
1	66	47.1%	44.3		22
2	40	28.6%	42		20.6
3	7	5%	10.4		16.9
4-5	0	0%			12.1-5.9
HKLC				P < 0.001
1	93	67.4%	47		79.7
2a	10	7.3%	19		33.4
2b	18	13%	34.7		32.7
3a	5	3.6%	10.4		12.5
3b	10	7.3%	20.8		5.5
4a	1	0.7%	17.8		3.9
4b	1	0.7%	3.1		1.9
5 (a/b)	0	0%			32.5/1.6
Tokyo				P = 0.002
0	10	7.1%	93.5
1	48	34.3%	47
2	41	29.3%	43.6
3	21	15%	30.3
4	14	10%	20.8
5	4	2.9%	10.4
6	1	0.7%	10.3
7	0	0%
8	1	0.7%	0.8
Okuda				P = 0.026
1	102	72.9%	45.5		15.8
2	36	25.7%	20.5		3.6
3	2	1.4%	0.8		1.3
GRETCH				P < 0.001
A	75	53.6 %	57.6		29.3
B	62	44.3 %	30		7.4
C	3	2.1 %	7.8		2.1
NIACE				P = 0.001
0	77	55 %	45.7		44
1	10	7.1 %	43		22
1.5	39	27.9 %	21.7		20
2.5	5	3.6 %	10.4		14
3	6	4.3 %	16.5		9
4	3	2.1 %	3.1		7
> 4	0	0 %			4
MESH				P < 0.001
0	40	28.6 %	57.9		66
1	46	32.9 %	43		37
2	30	21.4 %	19.5		21
3	19	13.6 %	20.8		10
4	5	3.5 %	10.4		5
> 4	0	0 %			4
ALBI				P = 0.008
1	43	31.9 %	79.2		24.7
2	87	64.4 %	34.7		11.4
3	5	3.7 %	15.7		4.9
ALBI				P = 0.008
2a	53	39.2 %	44.3		14.5
2b	34	25.2 %	25.2		6.6
BCLC based on ALBI				P = 0.048
0	15	10.9 %	> 81.1
A	75	54.3 %	44.9
B	20	14.5 %	22.2
C	1	0.7 %	3.1
D	27	19.6 %	21.7
ALBI-T				P = 0.002
0	12	9 %	93.5		137.7
1	42	31.6 %	63.1		83.2
2	49	36.8 %	42		53.4
3	28	21.1 %	21.3		27.4
4	2	1.5 %	0.8		5
5	0	0 %			1.4
HAP				P = 0.004
A	31	22.2 %	45.7		25.5
B	51	36.4 %	45.7		18.1
C	41	29.3 %	35.7		8.9
D	17	12.1 %	20.6		5.9
STATE				P = 0.322	20.5 (≥ 18 points)
> 37	8	5.7 %	25.2
27-37	17	12.1 %	40.6
18-27	16	11.4 %	44.9
< 18	13	9.3 %	20
Median STATE score	29.1 (range: 2.4 – 45.6)				6.1
SNACOR				P = 0.09
0-2	31	22.1 %	25.2		31.5
3-6	17	12.1 %	19		19.9
7-10	1	0.7 %	10.3		9.2
NSP				P = 0.03
0	63	45 %	79.2
1	49	35 %	42
2	11	7.9 %	14.9
3	10	7.1 %	20
4	4	2.9 %	22.2
5	3	2.1 %	5.6
NSP				P = 0.002
0-1	13	9.3 %	47		51.5
> 1	25	17.9 %	20.5		17.3

Comparison with data in original studies which available. NS: Not significant. ALBI: Albumin-bilirubin; BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program; GRETCH: Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire; HAP: Hepatoma arterial embolization; HKLC: Hong Kong Liver Cancer; ITA.LI.CA: Italian Liver Cancer; JIS: Japanese Integrated Staging; MESH: Model to estimate survival for hepatocellular carcinoma patients; NSP: Needle and syringe programme; SNACOR: Tumor size and number, baseline alpha-fetoprotein, Child-Pugh and objective radiological response; STATE: Selection for Transarterial chemoembolization treatment.