Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria

Table 1 Features of liver transplant criteria for hepatocellular carcinoma and survival rates

Criteria	Single Tm LTD in cm	Multiple Tm as NN	Multiple Tm LTD in cm	TTD in cm	AFP in ng/mL	PIVKA II	Differ.	MiVi	LTD + NN	TTV in cm3	GGT in IU/L	5-yr DFS criteria in, %	5-yr OS criteria, %	5-yr recurrence criteria, %
Paul-Brousse	3	1-2	3	-	-	-	-	-	-	-	-	83	83	-
Milan	≤ 5	2-3	≤ 3	-	-	-	-	-	-	-	-	82 (4 yr)	85 (4 yr)	8
UCSF	≤ 6.5	2-3	≤ 4.5	≤ 8	-	-	-	-	-	-	-	-	75.2
BCLC	≤ 7	2-34-5	≤ 5≤ 7	-	-	-	-	-	-	-	-	-	80.2	23.8
Extended criteria	≤ 7.5	2-3	≤ 5	-	-	-	(> 5 cm with poor diff also excluded)	-	-	-		76.8 (4 yr)	82.9 (4 yr)	-
Berlin	≤ 6	No limit	≤ 6	≤ 15	-	-	-	-	-	-	-	64 (3 yr)	68 (3 yr)	-
Kyoto	≤ 5	2-10	≤ 5	-	-	≤ 400	-	-	-	-	-	-	86.7	4.9
Tokyo	≤ 5	2-5	≤ 5	-	-	-	-	-	-	-	-	94 (3 yr)	75	-
Onaca	≤ 6	2-4	≤ 5	-	-	-	-	-	-	-	-	64.6	-	-
Hangzhou	≤ 8	-	-	≤ 8	-	-	-	-	-	-	-	70.7	62.4	-
	> 8			> 8	≤ 400		Well/Moder
Asan	≤ 5	2-6	≤ 5	-	-	-	-	-	-	-	-	-	76.3	13.6 (3 yr)
CUN	≤ 6	2-3	≤ 5	-	-	-	-	-	-	-	-	-	73	-
Valencia	≤ 5	2-3	≤ 5	≤ 10	-	-	-	-	-	-	-	-	67	9
Shangai	≤ 9	2-3	≤ 5	≤ 9	-	-	-	-	-	-	-	52.6	78.1	10.7
Kyushu	≤ 5	No limit	≤ 5	-	-	≤ 300	-	-	-	-	-	87	82.7	-
UpToSeven	≤ 6	-	-	-	-	-	-	Neg.	≤ 7	-	-	-	71.2	39.9
TTV/AFP28	-	-	-	-	≤ 400	-	-	-	-	≤ 115	-	-	Approximately 60 (4 yr)	-
Ext Toronto	No limit	No limit	No limit	-	-	-	Well/Moder	-	-	-	-	-	68	25.6
AFP-TTD	≤ 8	-	-	≤ 8	≤ 400	-	-	-	-	-	-	74.4	-	4.9
Samsung	≤ 6	2-7	≤ 6	-	≤ 1000	-	-	-	-	-	-	89.6	-	-
5-5-500	≤ 5	2-5	≤ 5	-	≤ 500	-	-	-	-	-	-	73.2	75.8	7.3
Malatya	≤ 6	No limit	≤ 6	-	≤ 200	-	Well/Moder	-	-	-	≤ 104	-	79.7	-
Exp Malatya	≤ 10	No limit	≤ 10	-	≤ 200	-	-	-	-	-	≤ 104	-	77.6	-

AFP: Alpha fetoprotein; BCLC: Barcelona Clinic Liver Cancer; CUN: Clinica Universitaria de Navarra criteria; DFS: Disease-free survival; Differ: Differentiation; GGT: Gamma glutamyl transferase; LTD: Largest tumor diameter; MiVi: Microvascular invasion; Moder: Moderate; NN: Number of nodules; OS: Overall survival; PIVKA II: Protein induced vitamin K antagonist II; Tm: Tumor; TTD: Total tumor diameter; TTV: Total tumor volume; UCSF: University of California San Francisco criteria.

Table 2 Comparison of some improved criteria with Milan and expanded Malatya criteria on the basis of overall survival

Within criteria	Overall survival, %
	1-yr	3-yr	5-yr	10-yr
Milan	88.8	86.2	81.9	72.5
UCSF	89	83	75	67
Up to Seven	90	86	78	69
BCLC	89	83	76	68
ETC	88	78	70	61
Hangzhou	88	79	70	61
Malatya	90.1	85.2	79.7	72.8

BCLC: Barcelona Clinic Liver Cancer; ETC: Extended Toronto criteria; UCSF: University of California San Francisco.

Table 3 Scoring systems for liver transplantation in hepatocellular carcinoma and survival rates stratified according to the recurrence rates

Scoring system	Scores of the parameters						Post-transplant recurrence risk	5-yr DFS in low risk	5-yr OS in low risk	Recurrence in low risk at 5-yr
AFP Model[44], 2012	LTD: ≤ 3 cm; 3-6 cm; > 6 cm. Point: = 0; = 1; = 4		NN: 1-3 nodule; > 4 nodule. Point: = 0; = 2		AFP: ≤ 100; 100-1000; > 1000. Point: = 0; = 2; = 3		Total point = score (0-9): Score ≤ 2, low risk; Score > 2, high risk		67.8; 47.5	8.8; 50.6
RETREAT[45], 2017	LTD + NVT: 0; 1.1-4.9; 5.0-9.9; ≥ 10. Point: = 0; = 1; = 2; = 3		MiVi: Positive. Point: = 2		AFP at LT: 21-99; 21-99; 100-999; ≥ 1000. Point: = 0; = 1; = 2; = 3		Total point = score (0-8): Score = 0; Score < 5, low risk; Score ≥ 5, high risk (RR)			2.9; 75.2
MORAL[46], 2017	Pre-LT-MORAL: LTD > 3 cm; NLR > 5; AFP > 200. Point: = 3; = 6; = 4				Post-LT-MORAL: LTD > 3 cm; NN > 3 nodules; Grade 4 tumor; MiVi positive. Point: = 3; = 2; = 6; = 2		Total point = score (0-13): Score 0-2, low risk; Score 3-6, medium risk; Score 7-10, high risk; Score > 10, very high risk	97.4; 75.1; 49.9; 22.1
NYCA[47] 2018	LTD at diagnosis: 0-3 cm; > 3-6 cm; > 6 cm. Point: = 0; = 2; = 4		NN at diagnosis: 1 nodule; 2-3; ≥ 4. Point: = 0; = 2; = 4		AFP response: AFP always < 200; Point: = 0. Responders: Max > 200-1000 to final < 200; Point: = 2. Max > 1000 to final < 1000 (must be 50% drop); Point: = 2. Nonresponders: Max > 200-400 to final > 200; Point: = 3. Max > 400-1000 to final > 200; Point: = 4. Max > 1000 to final > 1000; Point: = 6		Total point = score (0-14): Score 0-2, low risk; Score 3-6, acceptable risk; Score ≥ 7, high risk	90; 70; 42		Cumulative: 7; 27.5; 62.5
Metroticket 2.0[48], 2018	LTD + NN ≤ 7 and AFP ≤ 200 or LTD + NN ≤ 5 and AFP 200-400 or LTD + NN ≤ 4 and AFP 400-1000						Low risk	87.4	78
SNAPP[49], 2020	LTD: ≤ 3 cm; 3-6 cm; > 6 cm. Point: = 0; = 1; = 2	NN: 1 nodule; 2-3 nodule; ≥ 4 nodule. Point: = 0; = 1; = 2		AFP and PIVKA II: AFP ≤ 150 + PIVKA II ≤ 100; AFP ≤ 150 + PIVKA II > 100; AFP > 150 + PIVKA II ≤ 100; AFP > 150 + PIVKA II > 100. Point: = 0; = 1; = 2; = 3		PET-CT: Isometabolic; Hypermetabolic. Point: = 0; = 1	Total point = score (0-8): Score ≤ 2, low risk; Score 3-4, medium risk; Score > 5, high risk	97; 71; 31		3; 29; 69

AFP: Alpha fetoprotein; DFS: Disease-free survival; LT: Liver transplantation; LTD: Largest tumor diameter; MiVi: Microvascular invasion; NLR: Neutrophile to lymphocyte ratio; NN: Number of nodules; NVT: Number of viable tumors; NYCA: New York/California; OS: Overall survival; PET-CT: Positron emission tomography computed tomography; PIVKA II: Protein induced vitamin K antagonist II; RETREAT: Risk Estimation of Tumor Recurrence After Liver Transplant.