Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States

Table 1 Characteristics of donors in the pre-direct-acting antivirals era and the post-direct-acting antivirals era

Characteristics		D-R-	D-R+	D+R-	D+R+	P value
n	Pre	116108	4646	550	2455
	Post	46099	1443	1082	1303
Age (median [IQR])	Pre	40.0 [23.0, 51.0]	40.0 [24.0, 51.0]	41.0 [34.0, 46.0]	42.0 [33.0, 49.0]	< 0.001
	Post	40.0 [27.0, 52.0]	42.0 [29.0, 52.0]	35.0 [29.0, 44.0]	32.0 [26.0, 39.0]	< 0.001
Gender = M (%)	Pre	69042 (59.5)	2762 (59.4)	380 (69.1)	1574 (64.1)	< 0.001
	Post	28136 (61.0)	853 (59.1)	617 (57.0)	818 (62.8)	0.012
BMI (median [IQR])	Pre	25.6 [22.4, 29.7]	25.6 [22.3, 29.4]	24.8 [22.1, 28.0]	25.1 [22.3, 28.6]	< 0.001
	Post	27.1 [23.4, 31.9]	27.5 [23.7, 32.2]	26.3 [23.3, 30.5]	25.6 [22.8, 29.4]	< 0.001
Race (%)
White	Pre	83490 (71.9)	3209 (69.1)	409 (74.4)	1824 (74.3)	< 0.001
African American		14085 (12.1)	698 (15.0)	91 (16.5)	341 (13.9)
Hispanic		14482 (12.5)	574 (12.4)	45 ( 8.2)	260 (10.6)
Other		4051 (3.5)	165 ( 3.6)	5 ( 0.9)	30 (1.2)
White	Post	31238 (67.8)	929 (64.4)	922 (85.2)	1103 (84.7)	< 0.001
African American		6325 (13.7)	273 (18.9)	44 (4.1)	58 (4.5)
Hispanic		6421 (13.9)	187 (13.0)	94 (8.7)	116 (8.9)
Other		2115 (4.6)	54 (3.7)	22 (2.0)	26 (2.0)
Cause of death (%)
Anoxia	Pre	19852 (17.1)	750 (16.1)	67 (12.2)	470 (19.1)	< 0.001
Cerebrovascular/stroke		44318 (38.2)	1800 (38.7)	196 (35.6)	985 (40.1)
Head trauma		48450 (41.7)	1926 (41.5)	281 (51.1)	960 (39.1)
Other		3488 (3.0)	170 (3.7)	6 (1.1)	40 (1.6)
Anoxia	Post	18056 (39.2)	574 (39.8)	779 (72.0)	882 (67.7)	< 0.001
Cerebrovascular/stroke		12337 (26.8)	397 (27.5)	109 (10.1)	127 (9.7)
Head trauma		14151 (30.7)	430 (29.8)	176 (16.3)	272 (20.9)
Other		1555 (3.4)	42 (2.9)	18 (1.7)	22 (1.7)
DCD = yes (%)	Pre	10101 (8.7)	368 (7.9)	11 (2.0)	105 (4.3)	< 0.001
	Post	10519 (22.8)	329 (22.8)	151 (14.0)	128 (9.8)	< 0.001
SCR (median [IQR])	Pre	1.0 [0.7, 1.3]	1.0 [0.7, 1.3]	0.9 [0.7, 1.2]	0.9 [0.7, 1.1]	< 0.001
	Post	0.9 [0.7, 1.4]	1.0 [0.7, 1.4]	0.9 [0.7, 1.3]	0.9 [0.7, 1.1]	< 0.001
History of diabetes = yes (%)	Pre	6712 (5.8)	254 (5.5)	14 (2.5)	95 (3.9)	< 0.001
	Post	3616 (7.8)	123 (8.5)	41 (3.8)	30 (2.3)	< 0.001
History of hypertension = yes (%)	Pre	28967 (24.9)	1137 (24.5)	114 (20.7)	576 (23.5)	0.038
	Post	13638 (29.6)	453 (31.4)	226 (20.9)	173 (13.3)	< 0.001
Smoking history = no (%)	Pre	78484 (67.6)	3039 (65.4)	234 (42.5)	1068 (43.5)	< 0.001
	Post	36564 (79.3)	1154 (80.0)	723 (66.8)	953 (73.1)	< 0.001

D(-/+) R(-/+), hepatitis C virus (-) or (+) donors into hepatitis C virus (-) or (+) recipients. BMI: Body mass index; DCD: Donation after circulatory death; IQR: Interquartile range; M: male; Pre: Pre-direct-acting antivirals era; Post: Post-direct-acting antivirals era; SCR: Serum creatinine.

Table 2 Characteristics of recipients in the pre-direct-acting antivirals era and the post-direct-acting antivirals era

Characteristics		D-R-	D-R+	D+R-	D+R+	P value
n	Pre	116108	4646	550	2455
	Post	46099	1443	1082	1303
Age (median [IQR])	Pre	53.0 [42.0, 61.0]	51.0 [44.0, 58.0]	57.0 [47.0, 65.0]	53.0 [47.0, 59.0]	< 0.001
	Post	55.0 [44.0, 64.0]	59.0 [52.0, 64.0]	60.0 [52.0, 67.0]	60.0 [55.5, 65.0]	< 0.001
Gender = M (%)	Pre	69448 (59.8)	3251 (70.0)	406 (73.8)	1995 (81.3)	< 0.001
	Post	27135 (58.9)	994 (68.9)	739 (68.3)	1017 (78.1)	< 0.001
BMI (median [IQR])	Pre	26.8 [23.6, 30.9]	26.1 [23.0, 29.9]	26.5 [23.6, 29.4]	26.4 [23.3, 29.8]	< 0.001
	Post	28.6 [24.9, 32.8]	27.8 [24.4, 31.6]	29.1 [25.7, 33.3]	27.8 [24.5, 31.5]	< 0.001
Race (%)
White	Pre	56376 (48.6)	1383 (29.8)	211 (38.4)	404 (16.5)	< 0.001
African American		34683 (29.9)	2447 (52.7)	290 (52.7)	1789 (72.9)
Hispanic		15940 (13.7)	517 (11.1)	27 (4.9)	201 (8.2)
Other		9109 (7.8)	299 (6.4)	22 (4.0)	61 (2.5)
White	Post	16501 (35.8)	334 (23.1)	494 (45.7)	267 (20.5)	< 0.001
African American		15762 (34.2)	784 (54.3)	392 (36.2)	855 (65.6)
Hispanic		9079 (19.7)	226 (15.7)	117 (10.8)	137 (10.5)
Other		4757 (10.3)	99 (6.9)	79 (7.3)	44 (3.4)
Insurance = nonprivate (%)	Pre	83051 (71.5)	3733 (80.3)	418 (76.0)	1831 (74.6)	< 0.001
	Post	37085 (80.4)	1265 (87.7)	831 (76.8)	993 (76.2)	< 0.001
Education level (%)
High school	Pre	44906 (38.7)	1923 (41.4)	222 (40.4)	1195 (48.7)	< 0.001
Technical		22531 (19.4)	931 (20.0)	86 (15.6)	450 (18.3)
Post high school degree		18972 (16.3)	494 (10.6)	59 (10.7)	254 (10.3)
High school	Post	19085 (41.4)	741 (51.4)	403 (37.2)	680 (52.2)	< 0.001
Technical		11577 (25.1)	369 (25.6)	280 (25.9)	318 (24.4)
Post high school degree		10687 (23.2)	230 (15.9)	331 (30.6)	214 (16.4)
ESRD (%)
Diabetes	Pre	32208 (27.7)	1193 (25.7)	178 (32.4)	783 (31.9)	< 0.001
Hypertension		30368 (26.2)	1745 (37.6)	221 (40.2)	1108 (45.1)
Other		53532 (46.1)	1708 (36.8)	151 (27.5)	564 (23.0)
Diabetes	Post	14439 (31.3)	477 (33.1)	438 (40.5)	601 (46.1)	< 0.001
Hypertension		12513 (27.1)	543 (37.6)	270 (25.0)	444 (34.1)
Other		19147 (41.5)	423 (29.3)	374 (34.6)	258 (19.8)
Dialysis time, day, (median [IQR])	Pre	1143 [708, 1691]	1344 [889, 2164]	976 [580, 1388]	1118 [603, 1596]	< 0.001
	Post	1661 [1043, 2373]	1999 [1364, 2988]	1257 [637, 1674]	1065 [593, 1661]	< 0.001
CPRA (median [IQR])	Pre	0.0 [0.0, 2.0]	0.0 [0.0, 2.0]	0.0 [0.0, 0.0]	0.0 [0.0, 0.0]	< 0.001
CPRA (mean [SD])	Post	19.3 (32.8)	20.5 (33.5)	9.4 (21.9)	9.3 (21.3)	< 0.001
PVD = yes (%)	Pre	5374 (4.6)	210 (4.5)	26 (4.7)	111 (4.5)	< 0.001
	Post	4590 (10.0)	186 (12.9)	118 (10.9)	148 (11.4)	0.001
Diabetes = yes (%)	Pre	38827 (33.4)	1491 (32.1)	225 (40.9)	1014 (41.3)	< 0.001
	Post	17213 (37.3)	583 (40.4)	521 (48.2)	714 (54.8)	< 0.001

D(-/+) R(-/+), hepatitis C virus (-) or (+) donors into hepatitis C virus (-) or (+) recipients. BMI: Body mass index; ESRD: End stage renal disease; IQR: Interquartile range; M: Male; Pre: Pre-direct-acting antivirals era; Post: Post-direct-acting antivirals era; CPRA: Calculated panel reaction antibody; PVD: Peripheral vascular disease.

Table 3 Characteristics of transplantation in the pre-direct-acting antivirals era and the post-direct-acting antivirals era

Characteristics		D-R-	D-R+	D+R-	D+R+	P value
n	Pre	116108	4646	550	2455
	Post	46099	1443	1082	1303
TX year (median [IQR])	Pre	2005 [2000, 2010]	2004 [1999, 2009]	2001 [1997, 2007]	2006 [2001, 2010]	< 0.001
	Post	2016 [2015, 2018]	2016 [2015, 2018]	2018 [2017, 2018]	2016 [2015, 2017]	< 0.001
Region (%)
1	Pre	4694 (4.0)	167 (3.6)	11 (2.0)	74 (3.0)	< 0.001
2		14123 (12.2)	661 (14.2)	112 (20.4)	823 (33.5)
3		17507 (15.1)	704 (15.2)	64 (11.6)	235 (9.6)
4		10816 (9.3)	414 (8.9)	29 (5.3)	136 (5.5)
5		17680 (15.2)	655 (14.1)	63 (11.5)	260 (10.6)
6		4356 (3.8)	156 (3.4)	6 (1.1)	7 (0.3)
7		9360 (8.1)	403 (8.7)	54 (9.8)	137 (5.6)
8		7738 (6.7)	252 (5.4)	23 (4.2)	55 (2.2)
9		7150 (6.2)	355 (7.6)	29 (5.3)	222 (9.0)
10		10186 (8.8)	457 (9.8)	104 (18.9)	192 (7.8)
11		12498 (10.8)	422 (9.1)	55 (10.0)	314 (12.8)
1	Post	1601 (3.5)	62 (4.3)	35 (3.2)	65 (5.0)	< 0.001
2		5404 (11.7)	182 (12.6)	151 (14.0)	349 (26.8)
3		6590 (14.3)	221 (15.3)	181 (16.7)	150 (11.5)
4		4526 (9.8)	173 (12.0)	45 (4.2)	67 (5.1)
5		8107 (17.6)	238 (16.5)	101 (9.3)	144 (11.1)
6		1911 (4.1)	55 (3.8)	13 (1.2)	6 (0.5)
7		3192 (6.9)	110 (7.6)	37 (3.4)	45 (3.5)
8		3130 (6.8)	86 (6.0)	5 (0.5)	44 (3.4)
9		3057 (6.6)	85 (5.9)	125 (11.6)	174 (13.4)
10		3507 (7.6)	79 (5.5)	195 (18.0)	84 (6.4)
11		5074 (11.0)	152 (10.5)	194 (17.9)	175 (13.4)
Shared (%)
Local	Pre	85197 (73.4)	3464 (74.6)	223 (40.5)	931 (37.9)	< 0.001
Regional		9559 (8.2)	377 (8.1)	124 (22.5)	591 (24.1)
National		21352 (18.4)	805 (17.3)	203 (36.9)	933 (38.0)
Local	Post	35095 (76.1)	1115 (77.3)	337 (31.1)	379 (29.1)	< 0.001
Regional		5349 (11.6)	157 (10.9)	345 (31.9)	348 (26.7)
National		5655 (12.3)	171 (11.9)	400 (37.0)	576 (44.2)
CIT (median [IQR])	Pre	18.0 [13.0, 23.1]	18.0 [13.0, 23.5]	20.0 [16.0, 26.0]	19.0 [15.0, 25.0]	< 0.001
	Post	16.7 [11.4, 22.6]	16.5 [11.0, 22.0]	18.4 [13.1, 23.8]	18.0 [12.3, 23.5]	< 0.001
HLA mismatch = 4-6 (%)	Pre	76253 (65.7)	3238 (69.7)	452 (82.2)	2151 (87.6)	< 0.001
	Post	35126 (76.2)	1170 (81.1)	894 (82.6)	1154 (88.6)	< 0.001
DGF = yes (%)	Pre	28919 (24.9)	1440 (31.0)	139 (25.3)	756 (30.8)	< 0.001
	Post	13468 (29.2)	496 (34.4)	222 (20.5)	284 (21.8)	< 0.001

D(-/+) R(-/+), hepatitis C virus (-) or (+) donors into hepatitis C virus (-) or (+) recipients. CIT: Cold ischemia time; DGF: Delayed graft function; HLA: Human leukocyte antigen; IQR: Interquartile range; Pre: Pre-direct-acting antivirals era; Post: Post-direct-acting antivirals era; TX: Transplantation.

Table 4 Patient survival and death-censored graft survival at 3 years in the pre-direct-acting antivirals era and the post-direct-acting antivirals era

Cohorts in comparison (%)			D-R+	D+R+	D-R-	D+R-	Absolute risk difference
Crude	Patient survival	Pre	86.7 (85.8, 87.7)	84.8 (83.4, 86.3)	89.6 (89.5, 89.8)	73.1 (69.4, 76.9)	-
		Post	88.1 (85.7, 90.5)	89.8 (87.7, 92)	91 (90.6, 91.3)	86.1 (77.6, 95.6)	-
	Death-censored graft survival	Pre	84.2 (83.1, 85.3)	82 (80.4, 83.6)	88.8 (88.6, 89)	80.1 (76.6, 83.7)	-
		Post	92.4 (90.6, 94.2)	94.2 (92.5, 96)	92.5 (92.2, 92.8)	92.6 (87.3, 98.3)	-
D+ vs D- in R+	Patient survival	Pre	86.3 (84.4, 88.2)	84.8 (82.8, 86.8)	-	-	3.3 (1.8, 4.7)
		Post	90.2 (85.5, 95)	88.7 (84, 93.7)	-	-	2.7 (-2.9, 8.1)
	Death-censored graft survival	Pre	83.6 (81.5, 85.8)	81.6 (79.4, 83.9)	-	-	3.1 (1.2, 5)
		Post	90.1 (85.5, 94.9)	92 (87.9, 96.3)	-	-	0.4 (-5, 6.1)
D+ vs D- in R-	Patient survival	Pre	-	-	85.3 (82.3, 88.4)	73.5 (69.8, 77.4)	8 (5.2, 10.9)
		Post	-	-	89.1 (83.6, 94.9)	88.6 (81.6, 96.2)	-0.3 (-5.9, 6.1)
	Death-censored graft survival	Pre	-	-	86.9 (83.9, 89.9)	80.4 (76.8, 84.1)	7.4 (4.3, 10.5)
		Post	-	-	92.2 (87.8, 96.8)	93.8 (88.5, 99.4)	-2.3 (-7.4, 2.1)
R+ vs R- in D+	Patient survival	Pre	-	80.9 (77.3, 84.6)	-	76.7 (72.8, 80.7)	0.1 (-2.9, 3.1)
		Post	-	88.4 (84.3, 92.8)	-	85.1 (75.4, 96)	1.1 (-6.1, 7)
	Death-censored graft survival	Pre	-	79.4 (75.5, 83.5)	-	80.6 (76.9, 84.6)	1.2 (-2.5, 4.9)
		Post	-	93 (89.6, 96.5)	-	92.3 (86.2, 98.8)	0.7 (-5, 5.4)
R+ vs R- in D-	Patient survival	Pre	86.7 (85.8, 87.7)	-	88.7 (87.8, 89.6)	-	2.6 (1.9, 3.2)
		Post	88.1 (85.7, 90.5)	-	89.5 (87.3, 91.8)	-	-0.5 (-3.3, 2.2)
	Death-censored graft survival	Pre	84.2 (83.1, 85.3)	-	86.5 (85.5, 87.5)	-	3.5 (2.6, 4.4)
		Post	92.4 (90.6, 94.2)	-	92.1 (90.2, 94.1)	-	-0.2 (-2.4, 2)
D+R+ vs D-R-	Patient survival	Pre	-	85 (83.4, 86.5)	89 (87.7, 90.4)	-	5.3 (4.3, 6.4)
		Post	-	88.4 (85.5, 91.4)	91.8 (89.2, 94.4)	-	3.3 (0, 6.7)
	Death-censored graft survival	Pre	-	82.7 (81, 84.4)	87.8 (86.4, 89.2)	-	7.1 (5.7, 8.5)
		Post	-	93.3 (90.9, 95.8)	93.3 (90.9, 95.8)	-	1.7 (-1.4, 4.5)
D+R- vs D-R+	Patient survival	Pre	85.4 (82.1, 88.8)	-	-	75.6 (71.6, 79.7)	5.4 (2.6, 8.6)
		Post	88.7 (81.8, 96.3)	-	-	91.5 (85, 98.6)	3.2 (-5.9, 11.6)
	Death-censored graft survival	Pre	84.5 (81.1, 88.1)	-	-	81.1 (77.3, 85.1)	4.8 (1.4, 8.2)
		Post	94.4 (89.3, 99.7)	-	-	93.3 (87.4, 99.5)	2.5 (-3.6, 10)

D(-/+) R(-/+), hepatitis C virus (-) or (+) donors into hepatitis C virus (-) or (+) recipients. Pre: Pre-direct-acting antivirals era; Post: Post-direct-acting antivirals era.