Hepatocellular carcinoma recurrence after liver transplant: An Australian single-centre study

Table 1 Baseline characteristics of patients with hepatocellular carcinoma with and without recurrence after liver transplantation, n (%)

Variable	Without recurrence (n = 109)	With recurrence (n = 10)	P value
Age at transplant (years)	56.8	55.8	0.68
Female	15 (14)	2 (20)	0.05
Male	94 (86)	8 (80)	0.58
Aetiology of liver disease
HCV	45 (41)	5 (50)	0.46
Alcohol	21 (19)	1 (10)	0.87
Alcohol +HCV	20 (18)	0 (0)	0.005
Non-alcoholic fatty liver disease	13 (12)	1 (10)	0.63
Hepatitis B virus	4 (4)	3 (30)	0.001
Primary sclerosing cholangitis	2(2)	0 (0)	0.74
Other	4 (4)	0 (0)	0.52
Child Pugh
A	32 (30)	1 (10)	0.78
B	40 (37)	6 (60)	0.25
C	37 (34)	3 (30)	0.94
Model for End-stage liver disease	15 ± 7.0	16 ± 7.4	0.64
Within Milan Criteria	102 (94)	9 (90)	0.81
Within University of California and San Francisco	105 (96)	10 (100)	0.82
Within Metroticket 2.0
Pre-transplant	101 (92)	9 (90)	0.55
Post-transplant	75 (68)	6 (60)	0.57
Comorbidities
Obesity	35 (32)	2 (20)	0.34
Overweight	43 (40)	6 (60)	0.17
Overweight or obese	78 (71)	8 (80)	0.60
Morphology at time of transplant
Number of nodules
1	85 (78)	7 (70)	0.74
2-3	22 (20)	3 (30)	0.21
> 3	2 (2)	0 (0)	0.78
Serum markers pre-transplant
AFP at time of transplant (ng/mL)	13.7 ± 30	41 ± 50	0.01
Highest pre-op AFP (ng/mL)	30.3 ± 64	41 ± 47	0.59
neutrophil-lymphocyte ratio at time of transplant	4.8 ± 13	2.9 ± 1.3	0.64
Biopsy pre-transplant performed	37 (34)	5 (50)	0.32
HCC treatment pre-transplant
Transarterial chemoembolization	25 (23)	3 (30)	0.56
Ablative techniques	19 (17)	3 (30)	0.78
Surgery	0	0 (0)	0.25
Radiology (selective internal radiation therapy/choline kinase)	9 (8)	0 (0)	0.65
Combined	24 (22)	4 (40)	0.10
Waiting time (days)	166 ± 180	194 ± 153	0.63
Explant histopathology findings
Number of viable nodules
0	8 (8)	1 (10)	0.14
1	45 (43)	3 (30)	0.24
2-3	37 (35)	2 (20)	0.46
> 3	16 (15)	4 (40)	0.001
Vascular invasion	25 (23)	4 (40)	0.003
Type of vascular invasion
Microvascular	25 (23)	3 (30)	0.001
Macrovascular	0 (0)	1 (10)	0.001
Viable HCC on explant	101 (92)	9 (90)	0.55
Histology grading
Well differentiated	44 (40)	1 (10)	0.001
Moderately differentiated	48 (44)	6 (60)	0.46
Poor differentiated	3 (3)	1 (10)	0.03

Quantitative data were expressed as mean ± SD. P values for the comparison between groups. Maximum diameter of viable tumour in mm. AFP: Alpha-fetoprotein; HCV: hepatitis C virus; HCC: Hepatocellular carcinoma.

Table 2 Predictors of post-transplant hepatocellular carcinoma recurrence

Variable	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age (years)	0.98 (0.91-1.05)	0.62
Male	1.55 (0.32-7.32)	0.57
Female	0.64 (0.13-3.03)	0.58
Obesity	0.56 (0.11-2.65)	0.46
Overweight	2.07 (0.58-7.35)	0.25
Histology pre-transplant performed	2.10 (0.60-7.31)	0.24
Explant tumour characteristics
Viable HCC on explant	0.72 (0.09-5.7)	0.76
Number of viable lesions
1	0.55 (0.05-5.3)	0.60
2-3	0.44 (0.04-4.8)	0.50
> 3	2.0 (0.22-17.9)	0.53
Max diameter of viable tumour (mm)	1.02 (0.98-1.06)	0.19
Sum of diameters (mm)	1.01 (0.96-1.0)	0.64
Macrovascular invasion	12.2 (1.47-102)	0.02	18.6 (1.98-174)	0.01
Microvascular invasion	1.75 (0.43-7.04)	0.42
Tumour differentiation
Well	1.52 (0.17-13.1)	0.58
Moderate	0.96 (0.10-8.6)	0.47
Poor	1.87 (1.63-80.5)	0.12
Serum markers
Highest Pre-op alpha-fetoprotein	1.00 (0.64-1.00)	0.64
neutrophil-lymphocyte ratio	0.90 (0.66-1.22)	0.51
Waiting time (days)	1.00 (0.99-1.00)	0.55
Cold Ischemia time (minutes)	1.00 (0.97-1.03)	0.70
Wait time from HCC diagnosis to liver transplantation
< 6 months	0.60 (0.17-2.15)	0.44
> 6 months	1.64 (0.46-5.85)	0.43

Results based on univariate and multivariate risk regression models. HCC: Hepatocellular carcinoma; HR: Hazard ratio.

Table 3 Characteristics of hepatocellular carcinoma recurrence after liver transplantation, n (%)

Variable	Overall (n = 10)
Time to recurrence (years)	2.9 ± 0.75
< 2	4 (40)
> 2	6 (60)
Location
Hepatic	1 (10)
Extrahepatic	9 (90)
Alpha-fetoprotein at time of recurrence (ng/mL)	4700 ± 9394
Treatment of recurrence
Yes	6 (60)
No	4 (40)
Type of treatment
Systemic therapy	1 (10)
Surgery	0 (0)
Radiotherapy	1 (10)
Combined	2 (20)
Other	2 (20)