Salvage living donor liver transplantation for posthepatectomy recurrence: a higher incidence of recurrence but promising strategy for long-term survival

Figures & data

Table 1 Univariate analysis of factors affecting recurrence-free survival

	n	Mean RFS (months)	HR, 95% CI	P-value
Age
<55	129	135.7	2.16 (1.10–4.23)	0.024
≥55	174	152.4	1
Gender
Female	59	125.0	1	0.679
Male	244	145.4	1.20 (0.50–2.89)
AFP (ng/mL)
<400	276	147.9	1	0.073
≥400	27	100.5	2.23 (0.93–5.36)
Hepatitis B virus
Yes	208	143.8	1.40 (0.66–2.98)	0.378
No	95	127.3	1
Hepatitis C virus
Yes	91	151.3	1	0.247
No	212	143.5	1.59 (0.73–3.49)
Child class
A	139	136.5	2.28 (1.14–4.55)	0.020
B, C	164	154.3	1
MELD score
<20	272	143.9	1.73 (0.41–7.20)	0.450
≥20	31	155.4	1
Year of transplantation
2001–2010	117	147.0	1	0.878
2011–2018	186	82.8	1.05 (0.53–2.07)
Transplantation type
Salvage	58	106.7	2.78 (0.41–5.50)	0.003
Primary	245	150.8	1
Previous treatment for HCC
Yes	253	143.4	1.55 (0.55–4.39)	0.407
No	50	154.2	1
Ascites (mL)
<1000	236	145.3	1	0.733
≥1000	67	144.0	1.14 (0.52–2.52)
Blood loss (mL)
<2000	197	144.3	1	0.860
≥2000	106	147.1	0.94 (0.46–1.91)
GRWR
<0.8%	69	135.8	1	0.758
≥0.8%	234	145.7	1.14 (0.50–2.60)
Graft type
Right liver graft	284	147.5	1	0.123
Left liver graft	19	81.8	2.27 (0.80–6.42)
Donor gender
Male	170	146.0	1.01 (0.52–1.95)	0.985
Female	133	131.9	1
Donor age
<40	253	148.7	1	0.070
≥40	50	130.6	2.01 (0.95–4.28)
Tumor number
≤3	233	153.2	1	0.001
>3	70	113.9	3.03 (1.57–5.83)
Maximum tumor size (cm)
≤5	276	147.4	1	0.338
>5	27	115.1	1.67 (0.59–4.72)
Sum of tumor size (cm)
≤8	248	153.6	1	<0.0001
>8	55	109.3	4.10 (2.12–7.95)
Histology grade
Grade 1, 2	229	151.5	1	0.005
Grade 3, 4	74	127.7	2.60 (1.33–5.04)
Microvascular invasion
Yes	53	105.1	1	<0.001
No	250	152.9	3.60 (1.85–6.99)
Milan
Within	201	158.2	1	<0.00001
Beyond	102	116.7	4.91 (2.45–9.84)
UCSF
Within	217	156.3	1	<0.0001
Beyond	86	115.6	4.23 (2.18–8.23)

Abbreviations: AFP, alpha-fetoprotein; MELD, model for end-stage liver disease; HCC, hepatocellular carcinoma; GRWR; graft recipient weight ratio; UCSF, university of california san francisco; RFS, recurrence-free survival.

Table 2 Multivariate analysis of all significant factors affecting recurrence-free survival

	p	Hazard ratio (95%CI)
Age <55 years	0.073	1.89 (0.94–3.82)
Child-Pugh class A	0.249	1.59 (0.72–3.52)
Salvage LDLT	0.025	2.49 (1.12–5.54)
Tumor number >3	0.630	0.76 (0.26–2.24)
Sum of tumor size >8 cm	0.437	1.44 (0.57–3.67)
Histology grade 3, 4	0.102	1.82 (0.88–3.77)
Microvascular invasion	0.103	1.92 (0.87–4.22)
Beyond Milan criteria	0.004	7.12 (1.86–27.25)
Beyond UCSF criteria	0.652	0.69 (0.14–3.39)

Abbreviations: LDLT, living donor liver transplantation; UCSF, university of california san francisco.

Table 3 Comparison of clinicopathological and demographic features of patients based on transplantation type

	Salvage LDLT	Primary LDLT	P-value
n=58 (%)	n=245 (%)
Age (years)
Median (range)	54 (13–69)	57 (33–70)	0.027
Gender
Female:Male	8:50	51:194	0.225
AFP (ng/mL)
Median (range)	9 (1.3–2181)	12 (1.7–18,250)	0.416
Hepatitis B virus
Yes	45 (77.6)	163 (66.5)	0.103
No	13 (22.4)	82 (33.5)
Hepatitis C virus
Yes	6 (10.3)	85 (34.7)	<0.001
No	52 (89.7)	160 (65.3)
Child class
A	42 (72.4)	97 (39.6)	<0.0001
B, C	16 (27.6)	148 (60.4)
MELD score
Median (range)	8.0 (5.0–18.0)	12.0 (6.0–36.0)	<0.0001
Pre-transplantation locoregional therapy
Yes	51 (87.9)	202 (82.4)	0.312
No	7 (12.1)	43 (17.6)
Ascites (mL)
Median (range)	0 (0–11,000)	0 (0–14,400)	<0.001
Blood loss (mL)
Median (range)	875 (100–13,000)	1400 (50–23,400)	0.012
Liver mobilization (min)
Median (range)	309 (182–518)	310 (165–532)	0.868
Total operative time (min)
Median (range)	680 (390–1025)	659 (352–1046)	0.239
GRWR
Median (range)	0.87 (0.51–1.44)	0.92 (0.58–1.79)	0.069
Graft type
Right liver graft	52 (89.7)	232 (94.7)	0.222
Left liver graft	6 (10.3)	13 (5.3)
Donor gender
Female:male	28:30	105:140	0.455
Donor age (years)
Median (range)	33 (18–58)	30 (18–55)	0.013
Tumor number
Median (range)	2 (1–20)	2 (1–22)	0.707
Maximum tumor size (cm)
Median (range)	2.0 (0.5–6.0)	2.5 (0.6–11.2)	0.018
Sum of tumor size (cm)
Median (range)	3.1 (0.5–20.1)	4.0 (0.6–20.1)	0.222
Histology grade
Grade 1, 2	43 (74.1)	186 (75.9)	0.777
Grade 3, 4	15 (25.9)	59 (24.1)
Microvascular invasion
Yes	13 (22.4)	40 (16.3)	0.273
No	45 (77.6)	205 (83.7)
Milan
Within	43 (74.1)	158 (64.5)	0.162
Beyond	15 (25.9)	87 (35.5)
UCSF
Within	44 (75.9)	173 (70.6)	0.425
Beyond	14 (24.1)	72 (29.4)
Hospital mortality	3 (5.2)	14 (5.7)	0.361

Abbreviations: LDLT, living donor liver transplantation; AFP, alpha-fetoprotein; MELD, model for end-stage liver disease; HCC, hepatocellular carcinoma; GRWR, graft recipient weight ratio; UCSF, university of california san francisco.

Figure 1 Kaplan–Meier survival curves in patients according to the type of living donor liver transplantation. (A) Recurrence-free survival (p=0.002). (B) Overall survival (p=0.326).

Table 4 Univariate and multivariate analyses of pretransplantation factors affecting HCC recurrence of patients after salvage living donor liver transplantation (n=58)

Factors (patient number)	Univariate analysis			Multivariate analysis
HR	95% CI	p-value	HR (95% CI)	p-value
Sex (male, female) (50 vs 8)	0.64	0.14–2.93	0.572	—	—
Hepatitis B virus (positive, negative) (52 vs 6)	0.49	0.11–2.25	0.365	—	—
Hepatitis C virus (positive, negative) (6 vs 52)	0.04	0.00–154.38	0.451	—	—
Liver resection
Age at LR (<55, ≥55 years) (41 vs 17)	2.16	0.47–9.75	0.316	—	—
Extent of LR (>3, <3 segments) (12 vs 46)	3.55	1.13–11.12	0.029	—	NS
Tumor number (single, multiple) (51 vs 7)	0.43	0.11–1.56	0.201	—	—
Maximum tumor size (≥5, <5 cm) (17 vs 41)	6.18	1.99–19.18	0.002	10.79 (2.10–55.43)	0.004
Microvascular invasion (yes, no) (7 vs 51)	1.82	0.40–8.29	0.435	—	—
Satellite nodule (yes, no) (12 vs 46)	1.72	0.53–5.60	0.365	—	—
Histology grade (I/II, III/IV) (46 vs 12)	0.74	0.16–3.34	0.697	—	—
Recurrent time after LR (≥1, <1 year) (40 vs 18)	1.90	0.64–5.68	0.246	—	—
Times of liver resection (1, >1) (52 vs 6)	1.86	0.41–8.48	0.419	—	—
Liver transplantation
Age at LT (<55, ≥55 years) (32 vs 26)	2.91	0.80–10.58	0.105	—	—
AFP (≥400, <400 ng/mL) (7 vs 51)	2.21	0.60–8.04	0.229	—	—
MELD score (≥20, <20) (0 vs 58)	—	—	—	—	—
Child class (A, B/C) (43 vs 15)	0.30	0.04–2.38	0.260	—	—
Tumor number (>3, ≤3) (11 vs 47)	4.48	1.49–13.43	0.007	—	NS
Maximum tumor size (>3, ≤3 cm) (11 vs 47)	3.74	1.20–11.60	0.022	—	NS
Milan criteria (beyond, within) (18 vs 40)	5.94	1.82–19.43	0.003	—	NS
UCSF (beyond, within) (13 vs 45)	7.25	2.34–22.46	0.001	—	NS

Abbreviations: HCC, hepatocellular carcinoma; LR, liver resection; LT, liver transplantation; AFP, alpha-fetoprotein; MELD, model for end-stage liver disease; UCSF, university of california at san francisco; NS, no significance.

Figure 2 The cumulative overall survival was calculated from the time of initial hepatocellular carcinoma diagnosis in patients who underwent salvage living donor liver transplantation.