Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation

Table 1 Donor demographics and graft variables

Characteristic		n = 99
Donor
Age/yr	Median (range)	45 (6-78)
Gender/male	n (%)	53 (55)
Warm ischemia time/min	Median (range)	29 (24-79)
Cold ischemia time/min	Median (range)	265 (129-453)
Graft
Macrosteatosis	Median % (range)	0 (0-40%)
Microsteatosis	Median % (range)	0 (0-90%)

Table 2 Recipient demographics

Characteristic		n = 99
Recipient
Age/yr	Median (range)	59 (18-72)
Gender/male	n (%)	61 (62)
MELD at transplant	Median (range)	21 (6-38)
Etiology
EtOH	n (%)	25 (26)
NASH	n (%)	23 (23)
HCC	n (%)	18 (18)
HCV	n (%)	9 (9)
Other	n (%)	24 (24)
Peak AST (Day 1-7)/(IU/L)	Median (range)	631 (144-13645)
Peak ALT (Day 1-7)/(IU/L)	Median (range)	506 (87-5002)
INR (Day 7)	Median (range)	1.1 (0.9-2.5)
Bilirubin (Day 7)/(mg/dL)	Median (range)	1.9 (0.5-16.8)

MELD: Model for end-stage liver disease; EtOH: Alcoholic hepatitis; NASH: Nonalcoholic steatohepatitis; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; AST: Aspartate transaminase; ALT: Alanine aminotransferase; INR: International normalized ratio.

Table 3 Donor demographics and graft variables based on macrosteatosis

Characteristic		< 30%	≥ 30%	P value
Donor macrosteatosis
Cohort	n (%)	94	5
Age/yr	Median (range)	45 (6-78)	28 (21-52)	0.21
Gender/male	n (%)	51 (55)	2 (40)	0.50
Warm ischemia time/min	Median (range)	29 (24-79)	32 (28-37)	0.60
Cold ischemia time/min	Median (range)	265 (129-453)	307 (248-422)	0.06
Graft
Macrosteatosis	Median % (range)	0 (0-10%)	30 (30-40%)
Microsteatosis	Median % (range)	0 (0-100%)	50 (0-70%)	0.001c

^cP < 0.001.

Table 4 Recipient demographics based on donor macrosteatosis

Characteristic		< 30%	≥ 30%	P value
Donor macrosteatosis
Recipient Cohort		94	5
Age/yr	Median (range)	59 (21-72)	39 (18-69)	0.01b
Gender/male	n (%)	57 (61)	4 (80)	0.36
MELD at transplant	Median (range)	21 (6-38)	14 (8-34)	0.90
Etiology
EtOH	n (%)	24 (26)	1 (20)
NASH	n (%)	20 (21)	3 (60)
HCC	n (%)	18 (19)
HCV	n (%)	9 (10)
Other	n (%)	23 (24)	1 (20)
Peak AST (Day 1-7)/(IU/L)	Median (range)	617 (144-13645)	5195 (321-9829)	0.001c
Peak ALT (Day 1-7)/(IU/L)	Median (range)	494 (87-4253)	1327 (398-5002)	0.004b
INR (Day 7)	Median (range)	1.1 (0.9-2.5)	1.1 (1.0-1.5)	0.60
Bilirubin (Day 7)/(mg/dL)	Median (range)	1.9 (0.5-11)	4.6 (1.3-16.8)	0.03a
No EAD	n (%)	77 (82)	2 (40)
EAD	n (%)	17 (18)	3 (60)	0.04a

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

MELD: Model for end-stage liver disease; EtOH: Alcoholic hepatitis; NASH: Nonalcoholic steatohepatitis; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; AST: Aspartate transaminase; ALT: Alanine aminotransferase; INR: International normalized ratio; EAD: Early allograft dysfunction.

Table 5 Donor and recipient demographics for mRNA expression of grafts

Characteristic		< 30%	≥ 30%	P value
Donor
Cohort	n (%)	18	4
Age/yr	median (range)	46 (6-70)	27 (21-45)	0.13
Gender/male	n (%)	11 (61)	2 (50)	0.68
Warm ischemia time/min	Median (range)	29 (24-63)	33 (28-37)	0.93
Cold ischemia time/min	Median (range)	270 (203-296)	341 (248-422)	0.003b
Graft
Macrosteatosis	Median % (range)	2 (0-10%)	30 (30-40%)
Microsteatosis	Median % (range)	7.5 (0-80%)	45 (0-70%)	0.07
Recipient
Age/yr	Median (range)	58 (35-69)	40 (18-69)	0.07
Gender/male	n (%)	12 (67)	4 (100)	0.09
MELD-Na at transplant	Median (range)	21 (8-29)	14 (8-34)	0.66
Etiology
EtOH	n (%)	3 (17)	1 (25)
NASH	n (%)	7 (39)	3 (75)
HCC	n (%)	5 (28)
HCV	n (%)	1 (5)
Other	n (%)	2 (11)
Peak AST (Day 1-7)/(IU/L)	Median (range)	630 (212-12987)	3143 (321-9232)	0.12
Peak ALT (Day 1-7)/(IU/L)	Median (range)	494 (95-4253)	1018 (398-5002)	0.16
INR (Day 7)	Median (range)	1.1 (0.9-1.3)	1.1 (1.0-1.5)	0.45
Bilirubin (Day 7)/(mg/dL)	Median (range)	1.9 (0.6-9.6)	4.0 (1.3-16.8)	0.06
OLTHOFF EAD Index
No EAD	n (%)	16 (89)	2 (50)
EAD	n (%)	2 (11)	2 (50)	0.10

^bP < 0.01.

MELD: Model for end-stage liver disease; EtOH: Alcoholic hepatitis; NASH: Nonalcoholic steatohepatitis; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; AST: Aspartate transaminase; ALT: Alanine aminotransferase; INR: International normalized ratio; EAD: Early allograft dysfunction.

Table 6 mRNA expression levels of donor grafts with ≥ 30% macrosteatosis

Gene name	Accession number	Counts in ≥ 30%	Count in < 30%	Fold difference
CCL20	NM_004591.1	1,722	357	+4.8
S100A12	NM_005621.1	1,052	327	+3.2
S100A8	NM_002964.4	5,919	2,487	+2.4
S100A9	NM_002965.3	8,959	4,030	+2.2
C3	NM_000064.2	5,543	8,484	-1.5
IGFBP1	NM_000596.2	2,048	3,093	-1.5
FN1	NM_212482.1	1,833	2,736	-1.5
CFB	NM_001710.5	8,096	11,359	-1.4
CRP	NM_000567.2	33,132	45,455	-1.4

CCL20: Chemokine (C-C motif) ligand 20; S100A12: S100 calcium binding protein A12; S100A8: S100 calcium binding protein A8; S100A9: S100 calcium binding protein A9; C3: Complement C3; IGFBP1: Insulin like growth factor binding protein 1; FN1: Fibronectin 1; CFB: Complement factor B; CRP: C-reactive protein.