Characteristics and risk factors for recurrence of nonalcoholic steatohepatitis following liver transplantation

Figures & data

Figure 1. Flow chart of patient enrollment. NASH: nonalcoholic steatohepatitis.

Table 1. Pretransplant characteristics of 95 LT recipients.

Variable	NASH (n = 27)	ALD (n = 68)	p Value
Recipient age, years, mean (range)	59.7 (38–69)	59.4 (36–72)	.88
Recipient sex (male/female)	21/6	57/11	.56
Body mass index, kg/m^2	31.3 (4.7)	28.6 (4.3)	.01
Body weight, kg	96.6 (17.3)	88.0 (17.3)	.03
MELD score	15.3 (6.7)	17.0 (6.8)	.26
Diabetes mellitus			<.001
Noninsulin-dependent	7 (26%)	2 (3%)
Insulin-dependent	15 (56%)	14 (21%)
Hepatocellular carcinoma	15 (56%)	16 (24%)	.004
Bilirubin, mg/dL	2.0 (0.5–9.8)	2.4 (0.4–34.3)	.24
Creatinine, mg/dL	1.0 (0.4–2.9)	0.9 (0.5–4.2)	.75
Albumin, mg/dL	2.8 (1.7–3.8)	2.8 (1.5–4.5)	.56
Aspartate aminotransferase, U/L	55 (21–126)	49 (19–209)	.24
Alanine aminotransferase, U/L	41 (16–78)	29 (7–112)	.01
Triglyceride, mg/dL	85 (50–274)	73 (31–345)	.02
Total cholesterol, mg/dL	120 (54–185)	135 (35–251)	.046

LT: liver transplantation; NASH: nonalcoholic steatohepatitis; ALD: alcoholic liver disease; MELD: model for end-stage liver disease.

Table 2. Biochemistry at 3 months after LT.

Variable	NASH (n = 22)	ALD (n = 52)	p Value
Within 72 h after LT
Peak AST level, U/L	1066 (186–9780)	1398 (170–7095)	.51
Three months after LT
Body mass index, kg/m^2	29.1 (3.6)	25.7 (4.0)	.001
Body weight, kg	90.4 (13.7)	78.7 (15.8)	.004
Albumin, g/dL	3.5 (0.6)	3.6 (0.4)	.27
Total bilirubin, mg/dL	0.5 (0.1–1.3)	0.4 (0.2–3.9)	.48
AST, U/L	27 (13–74)	23 (13–113)	.06
ALT, U/L	37 (11–277)	23 (11–78)	.11
Triglyceride, mg/dL	150 (81–460)	133 (58–549)	.36
Total cholesterol, mg/dL	170 (69–255)	181 (42–367)	.28

LT: liver transplantation; NASH: nonalcoholic steatohepatitis; ALD: alcoholic liver disease; AST: aspartate aminotransferase; ALT: alanine aminotransferase.

Table 3. Biochemistry and histological findings at one year after LT.

Variable	NASH (n = 22)	ALD (n = 52)	p Value
Body mass index, kg/m^2	30.9 (4.5)	26.9 (4.2)	<.001
Body weight, kg	95.8 (15.8)	82.2 (15.2)	.009
Increase in body weight, kg	1 (−25–17)	−5 (−23–12)	.21
Albumin, g/dL	3.4 (0.5)	3.7 (0.3)	.02
Total bilirubin, mg/dL	0.6 (0.2–1.9)	0.5 (0.2–1.7)	.15
AST, U/L	25 (14–164)	25 (13–78)	.30
ALT, U/L	25 (10–265)	25 (10–121)	.74
Triglyceride, mg/dL	195 (78–593)	133 (52–770)	.049
Total cholesterol, mg/dL	139 (35–386)	179 (23–344)	.006
HbA1c, mmol/mol	47.6 (14.6)	41.8 (10.2)	.06
Alcohol relapse	0 (0%)	7 (11%)	.03
Use of mTOR inhibitor	5 (19%)	2 (3%)	.01
Use of statin	6 (27%)	4 (8%)	.06
Histological findings (1-year biopsy)
Steatosis	–	–	.39
Grade 0	8 (36%)	28 (53%)	–
Grade 1	7 (32%)	16 (31%)	–
Grade 2	4 (18%)	4 (8%)	–
Grade 3	3 (14%)	4 (8%)	–
Perisinusoidal fibrosis	–	–	.64
Grade 0	11 (50%)	18 (34%)	–
Grade 1	9 (40%)	28 (54%)	–
Grade 2	1 (5%)	4 (8%)	–
Grade 3	1 (5%)	2 (4%)	–
Hepatocyte ballooning	9 (41%)	16 (31%)	.43
Rejection activity index	–	–	.85
≤2	17 (77%)	39 (75%)	–
3	2 (9%)	7 (13%)	–
≥4	3 (14%)	6 (12%)	–

LT: liver transplantation; NASH: nonalcoholic steatohepatitis; ALD: alcoholic liver disease; AST: aspartate aminotransferase; ALT: alanine aminotransferase.

Table 4. Risk factors for post-LT development of fatty liver disease in 74 patients with NASH and ALD: univariate and multivariate analyses.

	Univariate analysis			Multivariate analysis
Variable	OR	95% CI	p Value	OR	95% CI	p Value
Recipient, pre-LT
Age	1.07	0.99–1.14	.047	1.08	1.01–1.18	.04
Sex, male	0.91	0.28–2.84	.86	–	–	–
Body mass index	1.08	0.98–1.21	.14	–	–	–
MELD score	0.97	0.91–1.04	.42	–	–	–
Diabetes mellitus
None	1.00	–	–	–	–	–
Noninsulin-dependent	2.60	0.46–20.1	.28	–	–	–
Insulin-dependent	2.28	0.81–6.71	.12	–	–	–
Triglyceride	1.01	0.99–1.02	.11	–	–	–
Total cholesterol	1.00	0.99–1.01	.40	–	–	–
Recipient, 1-year post-LT
Body mass index	1.16	1.04–1.32	.007	1.16	1.02–1.35	.02
Triglyceride	1.00	0.99–1.01	.15	–	–	–
Total cholesterol	0.99	0.99–1.01	.45	–	–	–
HbA1c	1.04	0.99–1.09	.07	1.01	0.96–1.06	.74
Alcohol relapse	4.12	0.57–82.7	.17	–	–	–
Use of mTOR inhibitor	0.61	0.08–3.91	.60	–	–	–
Use of statin	10.9	1.88–206	.005	4.54	0.65–91.2	.14
Donor
Age	1.00	0.97–1.04	.90	–	–	–
Sex, male	1.00	0.38–2.60	>.99	–	–	–
Body mass index	0.93	0.80–1.06	.26	–	–	–
Cause of death	–	–	.65	–	–	–
CVA	1.14	0.31–4.13	–	–	–	–
Trauma	0.50	0.05–3.66	–	–	–	–
Others	1.00	–	–	–	–	–
Graft steatosis ≥20%	0.97	0.21–4.42	.97	–	–	–
Cold ischemia time	0.99	0.99–1.00	.77	–	–	–

LT: liver transplantation; NASH: nonalcoholic steatohepatitis; ALD: alcoholic liver disease; OR: odds ratio; CI: confidence interval; AST: aspartate aminotransferase; ALT: alanine aminotransferase; MELD: model for end-stage liver disease; CVA: cerebral vascular accident.

Table 5. Comparison of patients who developed NASH recurrence with those who did not.

Variable	Recurrence	No recurrence	p Value
	(n = 9)	(n = 13)
Recipient, pre-LT
Age, years, median (range)	64 (52–69)	57 (38–69)	.07
Sex (male/female)	6/3	12/1	.26
Body mass index, kg/m^2	30.9 (4.6)	31.4 (4.4)	.81
Diabetes mellitus	–	–	.009
Noninsulin-dependent	0	5 (38%)	–
Insulin-dependent	8 (89%)	4 (31%)	–
Albumin, g/dL	3.1 (2.3–3.8)	2.7 (1.8–3.5)	.28
Triglyceride, mg/dL	88 (58–274)	106 (50–265)	.71
Total cholesterol, mg/dL	120 (77–185)	108 (54–181)	.62
HbA1c, mmol/mol	48 (23)	37 (10)	.22
Recipient, 3 months post-LT
Body mass index, kg/m^2	29.1 (4.6)	29.1 (2.9)	.98
HbA1c, mmol/mol	39 (11)	37 (10)	.72
Recipient, 1-year post-LT
Body mass index, kg/m^2	31.2 (5.8)	30.6 (3.5)	.75
Albumin, mg/dL	3.5 (2.4–4.1)	3.6 (2.5–4.1)	.46
Triglyceride, mg/dL	168 (78–593)	212 (86–513)	.43
Total cholesterol, mg/dL	135 (89–386)	151 (35–228)	.97
HbA1c, mmol/mol	53 (17)	43 (11)	.12
Increase in body weight, kg	3.0 (−20–17)	−0.4 (−25–17)	.59
Increase in HbA1c, mmol/mol	15 (10)	5 (8)	.05
Use of mTOR inhibitor	1 (11%)	3 (23%)	.62
Use of statin	4 (44%)	2 (15%)	.18
Donor
Age, years, median (range)	71 (48–80)	62 (21–73)	.23
Sex (male/female)	5/3	7/6	.70
Body mass index, kg/m^2	26.1 (4.6)	24.9 (4.0)	.55
Cause of death	–	–	.17
CVA	7 (87%)	7 (54%)	–
Trauma	0 (0%)	2 (15%)	–
Others	1 (13%)	4 (31%)	–
Graft weight, g	1523 (407)	1734 (422)	.27
Cold ischemia time, min	482 (160)	411 (99)	.21
Graft steatosis >10	0	3 (25%)	.23

NASH: nonalcoholic steatohepatitis; LT: liver transplantation; CVA: cerebral vascular accident.