Cooper KM, Colletta A, Hathaway NJ, Liu D, Gonzalez D, Talat A, Barry C, Krishnarao A, Mehta S, Movahedi B, Martins PN, Devuni D. Delayed referral for liver transplant evaluation worsens outcomes in chronic liver disease patients requiring inpatient transplant evaluation. World J Transplant 2023; 13(4): 169-182 [PMID: 37388395 DOI: 10.5500/wjt.v13.i4.169]
Corresponding Author of This Article
Katherine M Cooper, MD, Doctor, Department of Medicine, UMass Chan Medical School, 55 Lave Ave North, Worcester, MA 01605, United States. katherine.cooper@umassmed.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Transplant. Jun 18, 2023; 13(4): 169-182 Published online Jun 18, 2023. doi: 10.5500/wjt.v13.i4.169
Table 1 Baseline and demographics, %
Characteristic
Delayed referral (n = 78)
Early referral (n = 82)
P value
Portion of sample
49
51
-
Age (yr)
59 (10)
57 (9)
0.19
Distance to center (miles)
43.0 [20.5–59.5]
43.5 [19.3–67.3]
0.74
Time since diagnosis (mo)
30 [12.3–60]
11 [3.75–55.5]
< 0.01
Gender
0.59
Female
39.7
43.9
Male
60.3
56.1
Race
0.49
Asian
1.3
3.7
Black or African American
1.3
1.2
Other/Unknown
17.9
12.2
White
79.5
82.9
Ethnicity
0.11
Hispanic/other
19.2
9.8
Non-Hispanic
80.8
90.1
Etiology
0.88
Autoimmune
5.1
4.9
Alcohol
43.6
53.7
Cryptogenic/cholestatic
5.1
6.1
Genetic
7.7
4.9
Hepatitis C
11.5
9.8
NASH
26.9
20.7
Blood type
0.36
A
37.2
27.2
B
16.7
19.8
AB
1.3
4.9
O
44.9
48.1
Table 2 Liver transplant evaluation data, %
Delayed
Early
P value
Transferred to center
48.7
51.2
0.75
MELD-Na (points)
27.2 (7)
27.0 (9)
0.87
TIPS placed
15.4
7.3
0.22
ICU stay
51.3
43.9
0.35
ICU d (#)
10 (9)
8 (7)
0.44
Pressor support
34.6
26.8
0.29
Declined for LT listing
17.9
15.9
0.72
Reasons declined
Psychosocial
30.0
12.5
0.38
Medical
20.0
25.0
Death
30.0
12.5
Other
20.0
50.0
Decompensations
Ascites
94.9
96.3
0.65
Jaundice
64.1
72.0
0.29
EVB
21.8
24.4
0.70
HE
70.7
70.5
0.98
HRS
59.8
62.8
0.69
HHT
21.8
14.6
0.24
SBP
21.8
18.3
0.58
ACLF grade
Grade 1
34.6
42.7
0.56
Grade 2
50.0
42.7
Grade 3
15.4
14.6
ACLF bilirubin
< 15 mg/dL
82.1
76.8
0.28
15-25 mg/dL
9.0
17.1
> 25 mg/dL
9.0
6.1
ACLF INR
< 1.8
62.8
62.2
0.78
1.8-2.5
28.2
25.6
> 2.5
9
12.2
ACLF lactate
< 1.5 mmol/L
73.1
80.5
0.16
1.5-2.5 mmol/L
15.4
6.1
> 2.5 mmol/L
11.5
13.4
ACLF creatinine
< 0.7 mg/dL
7.3
7.3
0.64
0.7-1.5 mg/dL
32.9
32.9
> 1.5 mg/dL
52.6
59.8
Table 3 Pre-transplant clinical and demographic factors, %
Delayed
Early
P value
Education
0.14
Highschool or less
62.6
50.7
College degree or more
14.7
23.4
Substance use
Smoking history
55.1
57.3
0.15
Drinking history
62.8
74.3
0.12
Sobriety period
< 0.01
< 6 mo
22.4
59.0
6 mo – 2 yrs
53.0
26.2
> 2 yrs
23.6
14.8
Psychosocial factors
Depression history
39.7
28.0
0.12
Trauma history
9.0
2.4
0.07
Public insurance
50.0
50.0
1.00
Non-English first language
20.5
13.6
0.24
Lives with family
78.2
80.2
0.75
Married/stable partner
67.5
52.4
0.05
Unstable housing
6.4
4.9
0.68
Military service history
3.8
8.6
0.21
Worked within 1 mo
7.7
22.2
<0.01
Worked within 1 yr
24.4
49.4
<0.01
Clinical care
Outpatient GI documentation
83.3
78.0%
Ascites on diuretics
90.7
90.3
0.94
Ascites with regular paracentesis
32.0
25.0
0.35
On lactulose/rifaximin
85.0
90.5
0.39
Midodrine
42.9
46.0
0.81
Regular labs
n = 59
n = 40
Low albumin
89.8
77.5
0.09
High ALT/AST
93.2
87.5
0.31
High INR
84.7
72.5
0.14
Prior decompensations
Ascites
96.2
87.8
0.05
Jaundice
66.7
68.3
0.83
Variceal bleed
35.9
29.3
0.37
Hepatic encephalopathy
78.2
64.2
0.06
Hepatorenal syndrome
35.9
31.7
0.58
Hepatic hydrothorax
11.5
9.8
0.72
Spontaneous bacterial peritonitis
21.8
24.4
0.68
Table 4 Predictors of transplant
Initial multivariate regression
Backward logistic regression
Wald
P value
OR
95%CI
Wald
P value
OR
95%CI
Age (yr)
3.45
0.06
0.94
0.9-1.0
4.62
0.03
0.95
0.9-1.0
Education (HS)
2.41
0.12
1.49
0.9-2.5
-
-
-
-
ICU stay (+)
1.12
0.29
0.38
0.1-2.3
-
-
-
-
ACLF grade (G3)
2.67
0.10
2.76
0.8-9.3
4.75
0.03
2.13
1.1-4.2
MELD (points)
0.58
0.45
1.07
0.9-1.3
-
-
-
-
Creatinine (mg/dL)
0.08
0.78
0.90
0.4-1.9
-
-
-
-
Sodium (mmol/L)
1.28
0.26
0.90
0.8-1.0
-
-
-
-
Bilirubin (mg/dL)
1.06
0.30
1.05
1.1-1.1
-
-
-
-
INR
1.28
0.26
0.42
0.1-1.9
-
-
-
-
WBC (×109/L)
0.03
0.86
0.99
0.8-1.2
-
-
-
-
Hematocrit (%)
1.34
0.25
0.94
0.9-1.0
-
-
-
-
Platelets (×109/L)
1.73
0.19
0.99
1.0-1.0
5.50
0.02
0.99
1.0-1.0
N-L ratio
3.65
0.06
0.89
0.8-1.0
5.15
0.02
0.90
0.8-1.0
Albumin (g/dL)
6.79
< 0.01
3.58
1.4-9.4
9.04
< 0.01
3.32
1.5-7.3
Malnutrition (+)
0.30
0.59
1.39
0.4-4.6
-
-
-
-
Cardiac dx (+)
0.06
0.82
0.83
0.2-3.9
-
-
-
-
Sex (Male)
7.29
< 0.01
14.8
2.1-105
3.02
0.08
2.38
0.9-6.3
Race (White)
1.24
0.27
0.42
0.1-1.9
-
-
-
-
Depression (+)
4.17
0.04
4.24
1.1-17
-
-
-
-
Time since dx (mo)
2.44
0.12
1.01
1.0-1.0
2.69
0.10
1.01
1.0-1.0
Pressor need (+)
0.28
0.60
0.56
0.1-4.8
-
-
-
-
Height (cm)
2.37
0.12
0.94
0.9-1.0
-
-
-
-
Weight (kg)
1.22
0.27
0.99
1.0-1.0
4.72
0.03
0.98
1.0-1.0
Transferred (+)
0.00
1.0
1.00
0.3-3.5
-
-
-
-
Refer to LTE (d)
0.04
0.85
1.00
1.0-1.0
-
-
-
-
Delayed referral (+)
2.67
0.10
0.32
0.1-1.2
3.51
0.06
0.40
0.2-1.0
Decompensations (#)
0.11
0.73
0.91
0.5-1.6
-
-
-
-
Etiology (ETOH)
0.00
0.98
1.00
0.7-1.5
-
-
-
-
TIPS (+)
1.36
0.24
0.52
0.2-1.6
-
-
-
-
Blood type (A)
2.50
0.11
0.62
0.3-1.1
2.71
0.01
0.65
0.4-1.1
Constant
3.26
0.07
5000
-
0.745
0.38
6.54
-
Table 5 Predictors of death
Initial multivariate regression
Backward logistic regression
Wald
P value
OR
95%CI
Wald
P value
OR
95%CI
Age (yrs)
5.51
0.02
1.12
1.0-1.2
6.24
0.01
1.10
1.0-1.1
Education (HS)
0.72
0.40
0.75
0.4-1.5
-
-
-
-
ICU stay (+)
0.03
0.86
0.84
0.1-5.8
-
-
-
-
ACLF grade (G3)
0.06
0.81
1.19
0.3-4.9
-
-
-
-
MELD (points)
4.58
0.03
0.73
0.5-1.0
-
-
-
-
Creatinine (mg/dL)
2.85
0.09
2.46
0.9-7.0
-
-
-
-
Sodium (mmol/L)
5.25
0.02
0.82
0.7-1.0
-
-
-
-
Bilirubin (mg/dL)
0.04
0.84
0.99
0.9-1.1
-
-
-
-
INR
3.06
0.08
8.85
0.8-101
-
-
-
-
WBC (×109/L)
0.02
0.88
1.02
0.8-1.3
-
-
-
-
Hematocrit (%)
1.57
0.21
1.11
0.9-1.3
2.67
0.10
1.09
1.0-1.2
Platelets (×109/L)
0.09
0.76
1.00
1.0-1.0
-
-
-
-
N-L ratio
5.90
0.02
1.22
1.0-1.4
5.47
0.02
1.11
1.0-1.2
Albumin (g/dL)
5.07
0.02
0.18
0.0-0.8
2.67
0.10
0.49
0.2-1.2
Malnutrition (+)
0.04
0.85
0.84
0.1-5.1
-
-
-
-
Cardiac dx (+)
1.71
0.19
3.53
0.5-23
-
-
-
-
Sex (Male)
4.43
0.04
0.08
0.0-0.8
-
-
-
-
Race (White)
1.06
0.30
0.32
0.0-2.8
-
-
-
-
Depression (+)
1.72
0.19
3.07
0.6-16
-
-
-
-
Time since dx (mo)
5.84
0.02
0.97
1.0-1.0
3.52
0.06
0.99
1.0-1.0
Pressor need (+)
0.36
0.55
0.44
0.0-6.5
-
-
-
-
Height (cm)
4.04
0.05
1.13
1.0-1.3
-
-
-
-
Weight (kg)
3.83
0.05
1.04
1.0-1.1
7.01
< 0.01
1.02
1.0-1.0
Transferred (+)
1.53
0.22
0.36
0.1-1.8
-
-
-
-
Refer to LTE (d)
0.65
0.42
0.99
1.0-1.0
-
-
-
-
Delayed referral (+)
6.75
0.01
8.40
1.7- 42
7.27
< 0.01
4.51
1.5-14
Decompensations (#)
3.61
0.06
2.08
1.0-4.4
6.33
0.01
1.49
1.1-2.0
Etiology (ETOH)
1.22
0.27
1.30
0.8-2.1
-
-
-
-
Blood type (A)
4.98
0.03
3.01
1.1-7.9
-
-
-
-
TIPS (+)
0.44
0.51
1.45
0.5-4.4
-
-
-
-
Constant
0.09
0.76
0.02
-
0.75
0.38
6.54
-
Citation: Cooper KM, Colletta A, Hathaway NJ, Liu D, Gonzalez D, Talat A, Barry C, Krishnarao A, Mehta S, Movahedi B, Martins PN, Devuni D. Delayed referral for liver transplant evaluation worsens outcomes in chronic liver disease patients requiring inpatient transplant evaluation. World J Transplant 2023; 13(4): 169-182