Risk factors for autoimmune liver disease recurrence after liver transplantation

Table 1 Variables included in predictive models

Model 1	Model 2	Model 3	Model 4
Time from diagnosis to LT	TB before LT	TB 3 months after LT	Age at LT
Age at LT	ALT before LT	ALT 3 months after LT	Sex
Sex	AST before LT	AST 3 months after LT	Socioeconomic status
Concomitant autoimmune disease1	ALB before LT	ALB 3 months after LT	Chronic kidney disease
Family history of autoimmune disease2	ALC before LT	ALC 3 months after LT	Infection history 6 months after LT
Child-Pugh score	ANC before LT	ANC 3 months after LT	History of acute transplant rejection
Model for end-stage liver disease-Na score	Infection history 6 months after LT	Infection history 6 months after LT
	History of acute transplant rejection	History of acute transplant rejection

¹Diagnosis of a concomitant autoimmune disease, distinct from autoimmune liver disease, before liver transplantation.

²History of autoimmune disease in first-degree or second-degree relatives.

ALC: Absolute lymphocyte count; ALB: Albumin; ALT: Alanine aminotransferase; ANC: Absolute neutrophil count; AST: Aspartate aminotransferase; LT: Liver transplantation; TB: Total bilirubin.

Table 2 Sociodemographics, clinical characteristics, outcomes, and treatment, n (%)

Characteristics	Full cohort (n = 79)	Recurrent AILD (n = 21)	Non-recurrent AILD (n = 58)	Odds ratio (95%CI)	P value
Age at diagnosis (years) (mean ± SD)	41.03 ± 11.94	37.29 ± 12.48	42.38 ± 11.55	0.96 (0.92-1.00)	0.098
Time from diagnosis to LT (years) (mean ± SD)	6.24 ± 4.15	6.48 ± 4.13	6.16 ± 4.19	1.01 (0.90-1.14)	0.760
Age at LT (years) (mean ± SD)	47.14 ± 11.75	43.76 ± 11.99	48.36 ± 11.53	0.96 (0.92-1.00)	0.128
Sex
Male	24 (30.4)	6 (28.6)	18 (31.0)	0.88 (0.29-2.66)	0.833
Female	55 (69.6)	15 (71.4)	40 (69.0)	1.0 (ref)
Socioeconomic status1
1	11 (13.9)	4 (19.0)	7 (12.1)	Ref	-
2	32 (40.5)	10 (47.6)	22 (37.9)	0.79 (0.18-3.35)	0.755
3	20 (25.3)	5 (23.8)	15 (25.9)	0.58 (0.11-2.86)	0.507
4	6 (7.6)	0 (0.0)	6 (10.3)	-	-
5	2 (2.5)	1 (4.8)	1 (1.7)	1.75 (0.08-36.28)	0.718
6	1 (1.3)	1 (4.8)	0 (0.0)	-	-
7	7 (8.9)	0 (0.0)	7 (12.1)	-	-
Family history of autoimmune disease2,3	12 (20.3)	3 (20.0)	9 (20.5)	0.97 (0.22-4.19)	0.970
Concomitant autoimmune disease4	23 (29.1)	7 (33.3)	16 (27.6)	1.31 (0.44-3.84)	0.620
Comorbidities
Type 2 diabetes mellitus	9 (11.4)	2 (9.5)	7 (12.1)	0.76 (0.14-4.02)	0.754
Chronic hypertension	6 (7.6)	0 (0.0)	6 (10.3)	-	-
Hypothyroidism	13 (16.5)	3 (14.3)	10 (17.2)	0.80 (0.19-3.24)	0.755
Chronic kidney disease	4 (5.1)	1 (4.8)	3 (5.2)	0.91 (0.09-9.33)	0.941
AILD etiology
AIH	30 (38.0)	8 (38.1)	22 (37.9)	Ref	-
PBC	19 (24.1)	4 (19.0)	15 (25.9)	0.73 (0.18-2.87)	0.657
AIH/PBC overlap	17 (21.5)	6 (28.6)	11 (19.0)	1.50 (0.41-5.40)	0.535
PSC	10 (12.7)	3 (14.3)	7 (12.1)	1.17 (0.24-5.69)	0.838
PSC/AIH overlap	2 (2.5)	0 (0.0)	2 (3.4)	-	-
PSC/PBC overlap	1 (1.3)	0 (0.0)	1 (1.7)	-	-
Child-Pugh score (mean ± SD)	10.86 ± 1.83	11.61 ± 1.16	10.58 ± 1.96	1.43 (1.03-2.00)	0.032
MELD score (mean ± SD)	19.86 ± 7.01	22.76 ± 5.47	18.81 ± 7.24	1.08 (1.01-1.16)	0.032
MELD-Na score (mean ± SD)	22.49 ± 6.81	24.71 ± 5.41	21.69 ± 7.12	1.06 (0.99-1.15)	0.085
Chronic liver disease complications5
Esophageal varices6	66 (91.7)	16 (88.9)	50 (92.6)	0.64 (0.10-3.82)	0.625
Portal thrombosis7	11 (14.7)	3 (15.8)	8 (14.3)	1.12 (0.26-4.76)	0.873
Hepatic encephalopathy	57 (72.2)	14 (66.7)	43 (74.1)	0.69 (0.23-2.05)	0.514
Ascites	70 (88.6)	20 (95.2)	50 (86.2)	3.20 (0.37-27.26)	0.287
Spontaneous bacterial peritonitis8	23 (30.3)	8 (40.0)	15 (26.8)	1.82 (0.62-5.32)	0.273
Hepatorenal syndrome9	6 (7.7)	1 (4.8)	5 (8.8)	0.52 (0.05-4.73)	0.562
Infection history 6 months after LT	46 (58.2)	12 (57.1)	34 (58.6)	0.94 (0.34-2.58)	0.906
History of acute transplant rejection10	12 (15.2)	4 (19.0)	8 (13.8)	1.47 (0.39-5.50)	0.567
Treatment following LT
Basiliximab11	57 (93.4)	16 (94.1)	41 (93.2)	1.17 (0.11-12.10)	0.895
Methylprednisolone12	71 (100)	18 (85.71)	53 (91.37)	-	-
Tacrolimus13	72 (98.6)	21 (100)	51 (98.1)	-	-
Mycophenolate13	64 (87.7)	18 (85.7)	46 (88.5)	0.78 (0.17-3.46)	0.747
Cyclosporine13	8 (11.0)	0 (0.0)	8 (15.4)	-	-
Prednisone13	73 (100)	21 (100)	52 (100)	-	-

¹Socioeconomic status was determined based on monthly income, ranging from ‘1’ for the lowest to ‘7’ for the highest.

²History of autoimmune disease in first-degree or second-degree relatives.

³Data for this variable was available in the electronic medical records of only 59 patients.

⁴Diagnosis of a concomitant autoimmune disease, distinct from autoimmune liver disease, before liver transplantation (LT).

⁵History of chronic liver disease complications at any time before LT.

⁶Data for this variable was available in the electronic medical records of only 72 patients.

⁷Data for this variable was available in the electronic medical records of only 75 patients.

⁸Data for this variable was available in the electronic medical records of only 76 patients.

⁹Data for this variable was available in the electronic medical records of only 78 patients.

¹⁰Acute transplant rejection was considered as rejection occurring within the first 4 months after LT.

¹¹Data for this variable was available in the electronic medical records of only 61 patients.

¹²Data for this variable was available in the electronic medical records of only 71 patients.

¹³Data for this variable was available in the electronic medical records of only 73 patients.

Logistic regression models were used to estimate crude odds ratio and their corresponding 95%CI. AIH: Autoimmune hepatitis; AILD: Autoimmune liver disease; LT: Liver transplantation; MELD: Model for end-stage liver disease; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis.

Table 3 Laboratory values before and at three months after liver transplantation, n (%)

Value	Full cohort (n = 79)	Recurrent AILD (n = 21)	Non-recurrent AILD (n = 58)	Odds ratio (95%CI)	P value
Before LT
TB (mg/dL) (mean ± SD)	11.67 ± 12.38	15.49 ± 12.95	10.28 ± 11.99	1.03 (0.99-1.07)	0.108
Direct bilirubin (mg/dL) (mean ± SD)	6.59 ± 7.39	8.70 ± 7.12	5.83 ± 7.40	1.04 (0.98-1.11)	0.137
Indirect bilirubin (mg/dL) (mean ± SD)	5.07 ± 5.34	6.80 ± 6.06	4.45 ± 4.96	1.07 (0.98-1.17)	0.099
ALT (U/L) (mean ± SD)	98.94 ± 132.33	136.94 ± 184.39	85.19 ± 106.34	1.00 (0.99-1.00)	0.147
AST (U/L) (mean ± SD)	144.35 ± 161.63	171.43 ± 177.24	134.54 ± 156.08	1.00 (0.99-1.00)	0.378
AST/ALT (mean ± SD)	1.83 ± 0.72	1.62 ± 0.64	1.91 ± 0.73	0.50 (0.21-1.20)	0.123
Alkaline phosphatase (U/L) (mean ± SD)	285.24 ± 199.90	326.67 ± 254.21	270.24 ± 176.48	1.00 (0.99-1.00)	0.272
Total proteins (g/dL) (mean ± SD)	6.41 ± 1.20	6.35 ± 1.56	6.43 ± 1.05	0.94 (0.61-1.43)	0.782
ALB (g/dL) (mean ± SD)	2.89 ± 0.66	2.70 ± 0.62	2.95 ± 0.67	0.53 (0.24-1.19)	0.128
Globulin (g/dL) (mean ± SD)	3.52 ± 1.36	3.65 ± 1.90	3.47 ± 1.12	1.09 (0.76-1.57)	0.611
ALB/globulin ratio (mean ± SD)	1.01 ± 0.60	1.01 ± 0.66	1.01 ± 0.59	1.01 (0.44-2.31)	0.981
Total leukocyte count (× 103/μL) (mean ± SD)	5.35 ± 3.35	5.47 ± 3.07	5.31 ± 3.47	1.01 (0.87-1.17)	0.848
ALC (× 103/μL) (mean ± SD)	0.82 ± 0.62	0.71 ± 0.46	0.86 ± 0.67	0.64 (0.26-1.59)	0.341
ANC (mean ± SD)	3.88 ± 3.05	4.12 ± 2.79	3.79 ± 3.16	1.03 (0.88-1.21)	0.669
TB > 3 (mg/dL)	61 (77.2)	42 (72.4)	19 (90.5)	3.61 (0.75-17.33)	0.108
ALT > 2 (ULN)	30 (37.9)	18 (31)	12 (57.1)	2.96 (1.06-8.28)	0.038
AST > 2 (ULN)	50 (63.2)	34 (58.6)	16 (76.2)	2.25 (0.72-7.00)	0.158
Three months after LT
TB (mg/dL) (mean ± SD)	1.08 ± 2.56	1.65 ± 4.63	0.84 ± 0.82	1.12 (0.89-1.41)	0.319
ALT (U/L) (mean ± SD)	61.45 ± 179.98	51.47 ± 105.78	65.47 ± 203.19	0.99 (0.99-1.00)	0.765
AST (U/L) (mean ± SD)	41.25 ± 113.26	35.46 ± 67.48	43.59 ± 127.69	0.99 (0.99-1.00)	0.783
ALB (g/dL) (mean ± SD)	4.13 ± 0.50	4.17 ± 0.33	4.11 ± 0.56	1.29 (0.44-3.77)	0.632
Creatinine (mg/dL) (mean ± SD)	0.90 ± 0.25	0.90 ± 0.21	0.90 ± 0.27	1.03 (0.13-7.70)	0.972
Total leukocyte count (× 103/μL) (mean ± SD)	4.47 ± 1.64	4.60 ± 1.42	4.42 ± 1.73	1.06 (0.78-1.45)	0.683
ALC (× 103/mL) (mean ± SD)	1.13 ± 0.73	0.94 ± 0.43	1.21 ± 0.80	0.50 (0.19-1.26)	0.146
ANC (mean ± SD)	2.76 ± 1.18	3.05 ± 1.01	2.65 ± 1.23	1.33 (0.86- 2.07)	0.197

Logistic regression models were used to estimate crude odds ratio and their corresponding 95%CI. ALB: Albumin; ALC: Absolute lymphocyte count; AILD: Autoimmune liver disease; ALT: Alanine aminotransferase; ANC: Absolute neutrophil count; AST: Aspartate aminotransferase; LT: Liver transplantation; TB: Total bilirubin; ULN: Upper limit normal.