Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation

Table 1 Patient and tumor characteristics according to recurrence rate, univariate analysis

Variables	Non-recurrent (n = 187)	Recurrent HCC (n = 37)	P-value
Patient characteristics
Age (yr)	52.05 ± 6.93	50.89 ± 6.88	0.354
Gender (male: female)	151 (80.7):36 (19.3)	33 (89.2):4 (10.8)	0.221
HBV: HCV: Other cause	164:11:12	33:2:2	0.965
Child-Pugh score	8.15 ± 2.41	8.14 ± 2.37	0.972
MELD score	12.76 ± 7.25	13.05 ± 9.45	0.858
GRWR (%)	1.20 ± 0.28	1.24 ± 0.24	0.454
≤ 1 (n = 29)	26 (89.7)	3 (10.3)	0.327
> 1 (n = 193)	159 (82.4)	34 (17.6)
AFP (ng/mL)	170.5 ± 806.2	249.94 ± 481.37	0.568
≤ 100 (n = 163)	142 (87.1)	21 (12.9)	0.025
> 100 (n = 59)	44 (74.6)	15 (25.4)
PIVKA-II (mAU/mL)	189.6 ± 1150.3	397.2 ± 674.5	0.576
≤ 100	99 (94.3)	6 (5.7)	0.018
> 100	14 (77.8)	4 (22.2)
Pre-transplant treatment			0.025
No (n = 57)	53 (93.0)	4 (7.0)
Yes (n = 167)	134 (80.2)	33 (19.8)
Pathologic characteristics
Maximal diameter (cm)	2.76 ± 1.98	5.54 ± 5.65	0.006
≤ 5 (n = 196)	170 (86.7)	26 (13.3)	< 0.001
> 5 (n = 20)	10 (50.0)	10 (50.0)
Total diameter (cm)	4.21 ± 2.88	7.82 ± 6.56	0.005
≤ 9 (n = 185)	162 (87.6)	23 (12.4)	0.001
> 9 (n = 19)	11 (57.9)	8 (42.1)
Tumor number	2.46 ± 2.18	3.06 ± 3.11	0.282
≤ 5 (n = 193)	164 (85.0)	29 (15.0)	0.046
> 5 (n = 22)	15 (68.2)	7 (31.8)
Microvascular invasion			0.039
No (n = 163)	140 (85.9)	23 (14.1)
Yes (n = 44)	32 (72.7)	12 (27.3)
E-S grade			0.300
Low (I, II) (n = 108)	93 (86.1)	15 (13.9)
High (III, IV)  (n = 81)	65 (80.2)	16 (19.8)

Data are expressed as absolute n (%) or mean ± SD. HBV: Hepatitis B virus; HCV: Hepatitis C virus; MELD: Model for End-Stage Liver Disease; GRWR: Graft vs recipient weight ratio; AFP: Alpha fetoprotein; PIVKA-II: Protein induced by vitamin K absence or angiotensin-II; E-S grade: Edmondson-Steiner grade.

Table 2 Risk factors for recurrence; multivariate analysis

Variables	P-value	Exp(B)	95%CI
AFP (100 ng/mL)	0.021	2.892	1.172-7.132
Pre-transplant treatment	0.114	2.421	0.742-7.897
Maximal diameter (5 cm)	< 0.001	11.891	3.784-37.368
Total diameter (9 cm)	0.142	2.633	0.754-9.194
Tumor number (5)	0.712	1.373	0.262-7.203
Microvascular invasion	0.27	1.768	0.653-4.784

AFP: Alpha fetoprotein; Exp(B): Exponentiation of the B coefficient.

Table 3 Recurrence rates according to various criteria n (%)

Variables	Non-recurrent	Recurrent	P-value
Milan criteria			0.021
Within (n = 133)	117 (88.0)	16 (12.0)
Beyond (n = 83)	63 (75.9)	20 (24.1)
UCSF criteria			0.002
Within (n = 154)	136 (88.3)	18 (11.7)
Beyond (n = 62)	44 (71.0)	18 (29.0)
CMC criteria			0.001
Within (n = 140)	126 (90.0)	14 (10.0)
Beyond (n = 74)	53 (71.6)	21 (28.4)
TNM			0.325
T1 (n = 81)	71 (87.7)	10 (12.3)
T2 (n = 127)	103 (81.1)	24 (18.9)
T3 (n = 7)	5 (71.4)	2 (28.6)
BCLC			< 0.001
0 (n = 36)	33 (91.7)	3 (8.3)
A (n = 82)	73 (89.0)	9 (11.0)
B (n = 53)	47 (88.7)	6 (11.3)
C (n = 45)	27 (60.0)	18 (40.0)
CLIP			0.023
0, 1 (n = 89)	73 (82.0)	16 (18.0)
2, 3 (n = 110)	97 (88.2)	13 (11.8)
4, 5 (n = 12)	7 (58.3)	5 (41.7)

UCSF: University of California, San Francisco; CMC: Catholic Medical Center; BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program; HCC: Hepatocellular carcinoma.

Table 4 Disease-free survival and overall survival rates according to various criteria

Criteria		Disease-free survival			Overall survival
		3 yr	5 yr	P-value	3 yr	5 yr	P-value
Milan	Within (n = 130)	0.880	0.867	0.009	0.808	0.798	0.137
	Beyond (n = 81)	0.730	0.704		0.733	0.706
UCSF	Within (n = 150)	0.881	0.869	0.001	0.822	0.813	0.009
	Beyond (n = 61)	0.681	0.645		0.677	0.643
CMC	Within (n = 138)	0.899	0.886	< 0.001	0.840	0.818	0.006
	Beyond (n = 71)	0.682	0.656		0.663	0.663
TNM	T1 (n = 80)	0.890	0.870	0.190	0.830	0.830	0.394
	T2 (n = 123)	0.788	0.773		0.753	0.725
	T3 (n = 7)	0.571	0.571		0.556	0.556
BCLC	0 (n = 35)	0.943	0.902	< 0.001	0.882	0.882	0.005
	A (n = 80)	0.878	0.878		0.805	0.787
	B (n = 52)	0.854	0.854		0.878	0.826
	C (n = 44)	0.578	0.544		0.549	0.549
CLIP	0,1 (n = 88)	0.795	0.771	0.011	0.776	0.776	0.272
	2,3 (n = 106)	0.885	0.870		0.819	0.792
	4,5 (n = 12)	0.556	0.556		0.509	0.509

UCSF: University of California, San Francisco; CMC: Catholic Medical Center; BCLC: Barcelona Clinic Liver Cancer; CLIP: Cancer of the Liver Italian Program.

Table 5 Comparison of the Milan and Catholic Medical Center criteria

Criteria		Recurrence rate	P-value	5-yr DFS	P-value	5-yr survival	P-value
Milan criteria
Single	≤ 5 cm (n = 91)	13%	< 0.001	0.862	< 0.001	0.829	< 0.001
	> 5 cm (n = 12)	61.5%		0.333		0.333
No. 2 or 3	≤ 3 cm (n = 39)	9.8%	0.889	0.878	0.891	0.711	0.251
	> 3 cm (n = 22)	8.7%		0.848		0.747
Number	≤ 3 (n = 164)	15.4%	0.209	0.824	0.228	0.781	0.316
	> 3 (n = 47)	21.7%		0.737		0.698
CMC criteria
Size ≤ 5 cm	AFP ≤ 100 (n = 138)	9.6%	0.001	0.886	< 0.001	0.818	< 0.001
Size ≤ 5 cm	AFP > 100 (n = 52)	20.0%		0.765		0.749
Size > 5 cm	AFP ≤ 100 (n = 15)	38.9%		0.514		0.508
Size > 5 cm	AFP > 100 (n = 4)	75.0%		0		0

CMC: Catholic Medical Center; DFS: Disease free survival; AFP: Alpha fetoprotein (mg/dL).