Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

Table 1 Characteristics of the study population, n (%)

Variable	COVID, n = 518	Pre-COVID, n = 675	Pvalue
Recipient
Age, yr, median (IQR)	64.0 (60.0, 67.8)	63.0 (59.0, 67.0)	0.2
Male	405 (78)	529 (78)	0.98
Race, White	328 (63)	388 (57)	0.12
African American	36 (6.9)	47 (7.0)
Hispanic	108 (21)	153 (23)
Asian	39 (7.5)	69 (10)
Others	7 (1.4)	19 (2.8)
BMI median (IQR) kg/m2	29.3 (25.7, 33.2)	28.9 (25.3, 33.0)	0.26
Etiology, HCV	180 (35)	258 (38)	0.034
HBV	33 (6.4)	43 (6.4)
ALD	95 (18)	149 (22)
NASH	118 (23)	107 (16)
Others	92 (18)	118 (17)
Blood Type, A	203 (39)	235 (35)	0.13
AB	18 (3.5)	27 (4.0)
B	76 (15)	82 (12)
O	221 (43)	331 (49)
Diabetes	208 (40)	255 (38)	0.4
HCV positive serostatus	229 (46)	319 (49)	0.28
Previous abdominal surgery	229 (45)	330 (49)	0.19
Portal vein thrombosis	66 (13)	106 (16)	0.19
Hemodialysis at transplant	8 (1.6)	8 (1.2)	0.59
TIPSS	30 (5.8)	32 (4.7)	0.42
AFP ng/mL, median (IQR)	6.0 (3.0, 15.0)	7.0 (4.0, 16.0)	0.21
MELD score, median (IQR)	10 (8, 14)	10 (8, 14)	0.33
MELD exception	510 (98)	658 (97)	0.24
Mechanical ventilation	0 (0)	2 (0.3)	0.51
Waiting days, median (IQR)	279 (221, 392)	300 (228, 424)	0.041
Patient location at transplant			0.62
ICU at time of transplant	2 (0.4)	5 (0.7)
Non-ICU inpatient at time of transplant	19 (3.7)	31 (4.6)
Outpatient	487 (96)	639 (95)
Donor
Age, yr, median (IQR)	45.0 (32.0, 59.0)	44.0 (30.0, 56.0)	0.027
Male	326 (63)	421 (62)	0.84
Race, White	322 (62)	428 (63)	0.058
African American	104 (20)	117 (17)
Hispanic	73 (14)	92 (14)
Asian	15 (2.9)	17 (2.5)
Others	4 (0.8)	21 (3.1)
BMI median (IQR) kg/m2	27.8 (24.4, 33.2)	27.0 (23.8, 30.9)	< 0.001
Blood Type, A	204 (39)	237 (35)	0.12
AB	14 (2.7)	16 (2.4)
B	80 (15)	88 (13)
O	220 (42)	334 (49)
HCV NAT positive	37 (7.1)	39 (5.8)	0.34
HCV antibody positive	59 (11)	76 (11)	0.94
Donor causes of death: Anoxia	234 (45)	265 (39)	0.026
Cerebrovascular accident	158 (31)	221 (33)
Head trauma	104 (20)	172 (25)
Central nervous system tumor	2 (0.4)	4 (0.6)
Others	20 (3.9)	13 (1.9)
Donor after cardiac death	62 (12)	80 (12)	0.95
Organ Share, Local	241 (47)	508 (75)	< 0.001
Regional	174 (34)	145 (21)
National	103 (20)	22 (3.3)
Donor risk index, median (IQR)	1.68 (1.45, 2.06)	1.59 (1.35, 1.91)	< 0.001

COVID: Coronavirus disease; IQR: Interquartile range; BMI: Body mass index; HCV: Hepatitis C virus; HBV: Hepatitis B virus; ALD: Alcoholic liver disease; NASH: Non-alcoholic steatohepatitis; TIPSS: Transjugular intrahepatic portosystemic shunt; AFP: Alpha-fetoprotein; MELD: Model for end-stage liver disease; ICU: Intensive care units; NAT: Nucleic acid amplification test.

Table 2 Pathological characteristics of hepatocellular carcinoma in liver transplant, n (%)

Variable	COVID, n = 518	Pre-COVID, n = 675	Pvalue
Number of tumors
1	229 (44)	333 (49)
2	116 (22)	146 (22)
3	80 (15)	77 (11)
4	36 (6.9)	47 (7.0)
5	22 (4.2)	33 (4.9)
6	31 (6.0)	38 (5.6)
Tumor numbers > 3	89 (17)	118 (17)	0.89
Outside UCSF criteria	131 (25)	178 (26)	0.71
Outside Milan criteria	203 (39)	262 (39)	0.84
Tumor max size, cm median (IQR)	2.80 (1.80, 4.00)	2.90 (1.90, 4.00)	0.92
Worst tumor histology
Complete tumor necrosis	132 (25)	185 (27)	0.5
Moderate differentiated	265 (51)	344 (51)
Poorly differentiated	26 (5.0)	41 (6.1)
Well differentiated	95 (18)	105 (16)
Vascular invasion	6 (1.2)	11 (1.6)	0.019
Macro
Micro	77 (15)	65 (9.6)
None	435 (84)	599 (89)
Lymph node involvement	8 (1.5)	4 (0.6)	0.1
Extra hepatic spread	7 (1.4)	6 (0.9)	0.76
Intrahepatic metastasis	42 (8.1)	36 (5.3)	0.066
Previous treatment for HCC	511 (99)	657 (97)	0.21
High risk features	174 (34)	198 (29)	0.12

COVID: Coronavirus disease; IQR: Interquartile range; UCSF: University of California San Francisco; HCC: Hepatocellular carcinoma.

Table 3 Outcomes of liver transplant for hepatocellular carcinoma, n (%)

Variable		COVID, n = 518	Pre COVID, n = 675	Pvalue
Month	March	68 (13)	132 (20)	0.008
	April	86 (17)	123 (18)
	May	108 (21)	97 (14)
	June	78 (15)	95 (14)
	July	84 (16)	99 (15)
	August	94 (18)	129 (19)
Distance from donor hospital, miles, median (IQR)		88 (23, 188)	50 (8, 164)	< 0.001
Cold ischemia time, hours median (IQR)		5.87 (4.71, 7.07)	5.78 (4.65, 7.12)	0.84
Acute rejection before discharge		17 (3.3)	11(1.6)	0.061
Treatment rejection within 6 month		27 (6.4)	38 (6.6)	0.88
Treatment rejection within 1 year		35 (8.4)	45 (8.4)	0.99
Length of stay, days median (IQR)		8 (6, 11)	8 (6, 12)	0.60
Survival rate
90-day overall survival		97.7	97.9	0.95
180-day overall survival		94.7	97.0	0.048
Two-year overall survival		86.5	91.7	0.0063
90 day graft survival		96.1	96.7	0.71
180 day graft survival		92.8	95.7	0.035
Two-year graft survival		84.5	89.6	0.014

IQR: Interquartile range; COVID: Coronavirus disease.

Table 4 Multivariable Cox regression analysis of factors affecting overall mortality

Variable	HR	95%CI	Pvalue
COVID period	1.85	1.28, 2.68	0.001
Recipient age	1.02	0.99, 1.05	0.15
Recipient diabetes	1.47	1.04, 2.06	0.027
MELD score	1.04	1.01, 1.07	0.016
Donor age	1.01	1.00, 1.02	0.10
Donation after cardiac death	0.59	0.31, 1.14	0.12
Pathology
Intrahepatic metastasis	2.03	1.20, 3.42	0.008
Lymph node invasion	2.49	0.90, 6.86	0.078
Worst tumor histology
Complete tumor necrosis	reference	-
Well differentiated	1.11	0.63, 1.97	0.70
Moderate differentiated	1.27	0.81, 1.99	0.30
Poorly differentiated	2.76	1.48, 5.15	0.001

HR: Hazard ratio; CI: Confidence intervals; MELD: Model for end-stage liver disease; COVID: Coronavirus disease.