SUPPLEMENTAL DIGITAL CONTENT
Figure Legends
Figure S1. Forest plot of studies estimating the prevalence of rejection (A), hepatic artery thrombosis (B), cytomegalovirus/Epstein-Barr virus infection (C), and biliary complications (D) posttransplant
Figure S2. Subgroup analyses of the pooled rate of hepatic artery thrombosis
Figure S3. Forest plot of studies estimating the rates of metabolic stability (A), liberalization of protein intake (B), reversal of pre-existing cardiomyopathy (C), and improvement of neurodevelopmental delay (D) posttransplant
Table S1 Search strategies Medline (PubMed)
Search
#1 propion*
#2 ((acidemia) OR acidaemia) OR aciduria
#3 #1 AND #2
#4 propionyl
#5 (coa) OR "coenzymea"
#6 #4 AND #5
#7 (((propionic) OR "PCCA") OR "PCCB") OR "PCC"
#8 (((deficien*) OR disorder) OR defect*) OR insufficien*
#9 #7 AND #8
#10 ((propionicaciduria) OR propionicacidemia) OR propionicacidaemia
#11 #3 OR #6 OR #9 OR #10
#12 (liver) OR hepatic
#13 (transplant*) OR graft*
#14 #12 AND #13
#15 liver transplantation [MeSH Terms]
#16 #14 OR #15
#17 #11 AND #16 Ovid Embase
# ▲ Searches
1 "propion*".af.
2 (acidemia or acidaemia or aciduria).af.
3 1 and 2 4 propionyl.af.
5 (coa or "coenzymea").af.
6 4 and 5
7 (propionic or "PCCA" or "PCCB" or "PCC").af.
8 (deficien* or disorder or defect* or insufficien*).af.
9 7 and 8
10 (propionicaciduria or propionicacidemia or propionicacidaemia).af.
11 3 or 6 or 9 or 10 12 (liver or hepatic).af.
13 (transplant* or graft*).af.
14 12 and 13
15 exp liver transplantation/
16 14 or 15 17 11 and 16 Cochrane Library
Searches
#1 ((((((propion*) AND (((acidemia) OR acidaemia) OR aciduria))) OR ((propionyl) AND ((coa) OR "coenzymea"))) OR ((((((propionic) OR "PCCA") OR "PCCB") OR "PCC")) AND ((((deficien*) OR disorder) OR defect*) OR insufficien*))) OR (((propionicaciduria) OR propionicacidemia) OR propionicacidaemia)):ti,ab,kw
#2 MeSH descriptor: [Liver Transplantation] explode all trees
#3 (liver or hepatic):ti,ab,kw
#4 (transplant* or graft*):ti,ab,kw
#5 #3 AND #4
#6 #2 OR #5
#7 #1 AND #6
Table S2 Quality assessment of case report studies and case series studies (according to Joanna Briggs Institute critical appraisal checklist for case reports and case series studies)
SUMMARY OF RISK OF BIAS ASSESSMENT IN CASE REPORT STUDIES
Study
Yorifuji et al, 2004
Manzoni et al, 2006
Amelook et al, 2011
Ryu et al, 2013
Arrizza et al, 2015
Honda et al, 2016
Silva et al, 2017
Moguilevitch et al, 2018
Tuchmann- Durand et al,
2020
Q1 Y Y U Y Y Y Y Y Y
Q2 U U U U Y N U U Y
Q3 U Y U U U Y Y Y U
Q4 Y Y U Y Y N Y U Y
Q5 U Y U U U U U Y N
Q6 Y Y U Y Y Y Y U U
Q7 U Y N Y U Y N U U
Q8 Y Y Y Y Y Y Y Y Y Total
score (max=16)
12 15 8 13 13 11 12 12 11
Q1: Were patient’s demographic characteristics clearly described?
Q2: Was the patient’s history clearly described and presented as a timeline?
Q3: Was the current clinical condition of the patient on presentation clearly described?
Q4: Were diagnostic tests or assessment methods and the results clearly described?
Q5: Was the intervention(s) or treatment procedure(s) clearly described?
Q6: Was the post-intervention clinical condition clearly described?
Q7: Were adverse events (harms) or unanticipated events identified and described?
Q8: Does the case report provide takeaway lessons?
Notes: Yes=2, Unclear=1, No=0, N/A = Not Applicable.
Low risk of bias: > 70% of total score (11 points);
SUMMARY OF RISK OF BIAS ASSESSMENT IN CASE SERIES STUDIES
Study
Kayler et al, 2002
Romano et al, 2010
Kasahara et al, 2012
Charbit- Henrion et
al, 2015
Critelli et al, 2018
Quintero et al, 2018
Celik et al, 2019
Chu et al, 2019
Ng et al, 2019
Pillai et al, 2019
Shanmuga m et al,
2019
Curnock et al, 2020
Q1 Y Y Y Y Y Y Y Y Y Y Y Y
Q2 Y N U Y Y Y U Y Y Y U U
Q3 U U Y Y Y Y Y Y U Y Y Y
Q4 N Y Y Y Y Y Y U Y Y U Y
Q5 Y N Y Y Y Y Y Y N Y Y Y
Q6 Y Y Y Y Y Y Y N Y Y Y Y
Q7 U Y U Y Y Y Y Y N Y Y Y
Q8 U U Y Y Y Y Y U Y Y Y Y
Q9 Y Y Y Y Y Y Y Y Y Y Y Y
Q10 Y Y Y Y Y Y Y Y Y Y Y Y Total
score (max=20)
15 14 18 20 20 20 19 16 15 20 18 19
Q1: Were the criteria for inclusion clearly defined?
Q2: Were the study subjects and the setting described in detail?
Q3: Was the source of information reliable?
Q4: Were valid methods used for identification of the condition for all participants?
Q5: Did the study subjects have consecutive inclusion of participants?
Q6: Was there clear reporting of the demographics of the participants?
Q7: Was there clear reporting of clinical information of the participants?
Q8: Were the outcomes or follow up results clearly reported?
Q9: Was statistical analysis appropriate?
Q10: Was the research value clearly clarified?
Notes: Yes=2, Unclear=1, No=0, N/A = Not Applicable.
Low risk of bias: > 70% of total score (14 points);
Table S3 Sensitivity analyses of the pooled rates of endpoints after excluding low-quality studies
Endpoint
Number of studies
Number of
patients Prevalence [95% CI]
Cochran’s Q
(P) I2 (%)
Patient survival 17 66 0.9515 [0.7982, 1.0000] 0.12 29.9
Graft survival 17 66 0.9090 [0.7093, 1.0000] 0.01 48.0
Occurrence of rejection 14 60 0.1942 [0.0427, 0.3922] 0.18 25.4
Occurrence of hepatic artery thrombosis 14 60 0.0964 [0.0084, 0.2340] 0.76 0
Occurrence of cytomegalovirus/Epstein-
Barr virus infection 14 60 0.1737 [0.0077, 0.4296] 0.01 53.0
Occurrence of biliary complications 14 60 0.0450 [0.0000, 0.1629] 0.81 0
Metabolic stability 13 52 0.9798 [0.8519, 1.0000] 0.33 11.8
Liberalization of protein intake 11 43 0.6113 [0.2758, 0.9081] 0.01 60.0
Reversal of pre-existing cardiomyopathy 6 9 1.0000 [0.7590, 1.0000] 1.00 0
Table S4 Subgroup analyses of the pooled rate of liberalization of protein intake
Group Number
of studies
Number of patients
Prevalence [95% CI] Cochran’s Q (P) I2 (%) Meta-regression (P)
Study design
Case report 5 8 0.8425 [0.2371, 1.0000] 0.15 40.2 Ref
Case series 8 37 0.5813 [0.2155, 0.9123] < 0.01 62.5 0.496
Geographical region
Asia 4 14 0.8346 [0.2282, 1.0000] 0.01 76.1 Ref
Europe 6 20 0.7143 [0.3595, 0.9785] 0.38 6.5 0.618
North America 3 11 0.2753 [0.0002, 0.7028] 0.34 8.7 0.085
Donor type
Living donor 7 18 0.6589 [0.1208, 1.0000] < 0.01 70.4 0.970
Decreased donor 7 27 0.6307 [0.3613, 0.8722] 0.46 0 Ref
Onset type
Early 11 34 0.5474 [0.2276, 0.8525] 0.10 38.1 Ref
Late 4 4 0.5000 [0.0000, 1.0000] 0.30 18.9 0.902
Indication for LT
Poor metabolic control 9 34 0.6644 [0.3109, 0.9525] 0.02 55.2 0.777
Cardiomyopathy 4 4 0.8218 [0.1676, 1.0000] 0.43 0 Ref
Preemptive treatment 3 7 0.5428 [0.0000, 1.0000] 0.14 49.4 0.621
Age at LT
> 1 year 12 40 0.6733 [0.3560, 0.9362] 0.03 49.5 0.404
< 1 year 5 5 0.3651 [0.0000, 0.9478] 0.35 9.9 Ref
