Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

Table 1 Clinicopathological characteristics of patients with hepatocellular carcinoma recurrence after living donor liver transplantation

Factors	Data, n (%)
Recipient age1	52.0 ± 8.1
Recipient sex, male	46 (85.2)
Etiology
Hepatitis B	46 (85.2)
Hepatitis C	2 (3.7)
Alcohol	5 (9.3)
Other	1 (1.9)
MELD score1	11.7 ± 8.5
GRWR1	1.28 ± 0.24
Pre-transplant locoregional treatment	48 (88.9)
Tumor marker at transplantation
AFP1	717.3 ± 1748.1 (median: 43.3)
HCC characteristics at pathology
Number1	2.4 ± 1.9 (median: 2.0)
Maximal tumor size (cm)1	4.85 ± 4.07 (median: 3.8)
Microvascular invasion	30 (60.0)
E-S grade III-IV	25 (52.1)
Beyond Milan criteria	38 (70.4)
Patterns of HCC recurrence
Time between LDLT and recurrence (mo)1	15.3 ± 23.9 (median: 6.5, range: 1-150)
Single vs multiple	14 (25.9) vs 40 (74.1)
Intrahepatic vs extrahepatic vs both	12 (22.2) vs 37 (68.5) vs 5 (9.3)
Recurrence organ
Lung	24 (44.4)
Liver	17 (31.3)
Bone	10 (18.5)

¹Values are shown as mean ± SD except where stated otherwise. MELD: Model for end-stage liver disease; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; E-S grade: Edmondson-Steiner grade; LDLT: Living donor liver transplantation.

Table 2 First treatment modalities for recurrent hepatocellular carcinoma after liver transplantation n (%)

Treatments	Curative	Palliative
	(n = 15, 27.8%)	(n = 39, 72.2%)
Operation	13 (86.7)	1 (2.6)
Operation and radiation	1 (6.7)	4 (10.3)
Operation and TACE		1 (2.6)
TACE		8 (20.5)
TACE and RFA	1 (6.7)	1 (2.6)
Radiation		7 (17.9)
Intravenous chemotherapy		5 (12.8)
Sorafenib		8 (20.5)
Conservative treatment		4 (10.3)

TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation.

Table 3 Differences of hepatocellular carcinoma recurrence patterns according to the Milan criteria at transplantation n (%)

Factors	Within Milan (n = 16)	Beyond Milan (n = 38)	P value
Recipient age1	47.4 ± 5.9	53.9 ± 8.1	0.005
Recipient sex, male	13 (81.3)	33 (86.8)	0.682
Etiology, hepatitis B	12 (75.0)	34 (89.5)	0.127
MELD score1	10.9 ± 9.1	12.0 ± 8.2	0.692
GRWR1	1.27 ± 0.20	1.28 ± 0.26	0.919
Pre-transplant locoregional treatment	13 (81.3)	35 (92.1)	0.346
Tumor marker at transplantation
AFP1	213.0 ± 371.8	829.6 ± 2040.7	0.043
HCC characteristics at pathology
Number1	1.2 ± 0.6	2.9 ± 2.0	< 0.001
Maximal tumor size1	2.33 ± 1.10	5.93 ± 4.41	< 0.001
Microvascular invasion	7 (50.0)	23 (63.9)	0.368
E-S grade III-IV	6 (46.2)	19 (54.3)	0.616
Recurrent HCC patterns
Recurrence rates	8.90%	33.60%	< 0.001
Time interval, median (mo) (LDLT-HCC recurrence)	7.0 (1-150)	6.0 (1-46)	0.157
	mean: 24.1 ± 39.5	mean: 11.5 ± 11.9
Single or Multiple			0.735
Single	5 (31.3)	9 (23.7)
Multiple	11 (68.7)	29 (76.3)
Recurrence site			0.555
Intrahepatic	5 (31.3)	7 (18.4)
Extrahepatic	10 (62.5)	27 (71.1)
Both	1 (6.3)	4 (10.5)
Survival after HCC recurrence, median (mo)	12.0 (3-122)	8.0 (1-62)	0.224
	mean: 24.0 ± 33.5	mean: 10.4 ± 10.5

¹Values are shown as mean ± SD except where stated otherwise. MELD: Model for end-stage liver disease; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; E-S grade: Edmondson-Steiner grade; LDLT: Living donor liver transplantation.

Table 4 Factors related with survival rates after hepatocellular caricnoma recurrence

Factors	Univariate analysis	Multivariate analysis
	P value	Harzard ratio (95%CI)	P value
Age > 60 yr	0.124
Male sex	0.739
Etiology	0.291
MELD score > 15	0.153
GRWR < 1.0	0.658
Pre-transplant treatments	0.170
Tumor state at transplantation
AFP > 100	0.575
Beyond Milan criteria	0.245
Microvascular invasion	0.384
E-S grade III-IV	0.227
Time to recurrence < 12 mo	0.010	2.408 (1.007-5.756)	0.048
Multiple recurrence	< 0.001	3.438 (1.072-11.025)	0.038
Recurrence site
Liver	0.824
Lung	0.937
Bone	0.695
Brain	< 0.001	2.966 (0.565-15.583)	0.199
Palliative treatment for recurrent tumors	< 0.001	3.886 (1.591-9.490)	0.003

MELD: Model for end-stage liver disease; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; E-S grade: Edmondson-Steiner grade.

Table 5 Clinicopathological characteristics in palliative treatment group between sorafenib and sirolimus treatment group and other treatment group n (%)

Factors	Sorafenib + Sirolimus	Other treatments	P value
Recipient age1	55.3 ± 9.1	51.6 ± 6.9	0.179
Recipient sex, male	9 (75.0)	24 (88.9)	0.348
Etiology, Hepatitis B	10 (83.3)	22 (81.5)	0.369
MELD score1	9.3 ± 3.3	14.0 ± 9.7	0.033
GRWR1	1.40 ± 0.27	1.23 ± 0.25	0.065
AFP at transplantation1	1038.3 ± 1849.2	256.5 ± 361.1	0.173
HCC characteristics at pathology
Number1	2.42 ± 2.02	2.38 ± 2.09	0.965
Maximal tumor size1	4.20 ± 2.06	5.44 ± 5.36	0.444
Beyond Milan criteria	9 (75.0)	17 (65.4)	0.714
Time between LDLT and recurrence, median	6 (range: 3-150)	5 (range: 1-46)	0.270
Patterns of HCC recurrence
Single or Multiple			0.219
Single	2 (16.7)	1 (3.7)
Multiple	10 (83.3)	26 (96.3)
Intrahepatic or Extrahepatic			0.074
Intrahepatic	0	9 (33.3)
Extrahepatic	10 (83.3)	15 (55.6)
Both	2 (16.7)	3 (11.1)
AFP at HCC recurrence1	7913.2 ± 16023.5	6139.5 ± 17794.2	0.772

¹Values are shown as mean ± SD except where stated otherwise. MELD: Model for end-stage liver disease; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; LDLT: Living donor liver transplantation.