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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Liver Transpl. Author manuscript; available in PMC Apr 1, 2012.
Published in final edited form as:
PMCID: PMC3078725
NIHMSID: NIHMS257704
Outcomes in Children Transplanted for Autoimmune Hepatitis
Steven R Martin,1 Fernando Alvarez,1 Ravinder Anand,2 Changhong Song,2 Wanrong Yin,2 and the SPLIT Research Group
1 Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal
2 The EMMES Corporation
Corresponding author: Steven R Martin MD, Gastroenterology & Nutrition, Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, Canada, T3B 6A8, Phone: 403 955-7721, Fax: 403 955-2992, stevenr.martin/at/albertahealthservices.ca
The outcomes of 113 children with autoimmune hepatitis (AIH), registered with Studies of Pediatric Liver Transplantation and transplanted between 1995 and 2006, were compared with those transplanted for other diagnoses (non-AIH). 4.9% of liver transplants were for AIH. 81% had AIH type 1 and most were transplanted for complications of chronic disease (60%), the majority in females (72%). Transplantation for fulminant AIH was more common in males (52.5% vs. 47.5% chronic, p=0.042). AIH patients differed from non-AIH by: age (13.0±0.4 vs. 4.6±0.1 years, p<0.0001), sex (64.6% female vs.52.9%, p=0.016), ethnicity (48.7% white vs. 58.2%, p<0.0001), initial immunosuppression (tacrolimus based: 72.6% vs. 62.6%, p=0.045; MMF use: 31.0% vs. 21.6 %, p=0.02) and immunosuppression at two years post-transplant (monotherapy: 51.9% vs.17.3%, p<0.0001). Late (>3 months), but not steroid-resistant or chronic rejection, was more common in AIH (log-rank p=0.0015). 5-year post-transplant survival for AIH was 86% (95%CI 73–93). Patient and graft survival, infectious and metabolic complications and re-transplantation rates did not differ between AIH and non-AIH groups. In conclusion, the higher risk for late acute rejection and greater degree of immunosuppression does not compromise outcomes of liver transplantation for AIH. Children transplanted for AIH in North America are typically female adolescents with complications of chronic AIH type 1 and include more children of African-American or Latino-American origin compared to the overall liver transplant population. These observations may inform detection, treatment and surveillance strategies designed to reduce the progression of autoimmune hepatitis and subsequently, the need for transplantation.
Keywords: Liver transplantation, Pediatrics, Late rejection, Outcome
Many patients with autoimmune hepatitis (AIH) already have cirrhosis at the time of diagnosis, and despite appropriate treatment, about 10%–15% of cases develop end-stage liver disease and require transplantation. (1) Almost 20%–25% of children with AIH, considering those with acute and chronic liver failure, will die or require liver transplantation while they are still children. (2) In adults, AIH is the underlying disease in 1.8–6% of those undergoing liver transplantation. (37) Adult patients transplanted for AIH experience acute cellular rejection and steroid-resistant rejection more frequently in the first year post-transplant than those transplanted for non-immune disorders.(510) Despite this increase in immune-mediated liver injury post-transplant, the long-term graft and patient survival, with a few exceptions, does not appear to be compromised.
As a consequence of its rarity few large pediatric series of AIH have been published. (1113) In the King’s College series, 52 patients were identified, of whom 10 (20%) required transplantation. One died awaiting transplantation while five (62.5%) experienced long-term survival. (11) Fulminant liver failure was the indication for transplantation in 4/9. In the Bicêtre series, 31 patients with type 1 AIH were followed. Two died of liver failure in the era prior to transplantation and 5 developed progressive liver failure, such that 7/31 (23%) could be considered to have required transplantation. (12) In contrast, in a recent pediatric series of 51 AIH patients who were followed for a median of 8 years, 28 (55%) came to transplantation. (13)
The Studies in Pediatric Liver Transplantation (SPLIT) registry was started in September 1995 and as of June 1st 2006, 44 participating centers in the United States and Canada registered 3161 children under the age of 18 years, of whom 2291 have received a first liver-only transplant. This represents approximately 56% of pediatric liver transplants in North America and includes the largest accumulation of data on children transplanted for AIH. The goal of this study was to determine the outcome of liver transplantation for AIH in children compared to the overall transplant population and to determine whether this outcome is influenced by the type of AIH or the mode of presentation.
Participation in the SPLIT registry was approved by each center’s institutional review board. Parents or legal guardians provided written informed consent and patient assent was obtained where appropriate. Enrolled patients were followed every 6 months until transplant. Post-transplant follow-up forms were sent every 6 months for 2 years, then annually until the patient’s 18th birthday. The timely, accurate and complete submission of data from each center was ensured by the Data Quality Committee, a subcommittee of the Scientific Advisory Board. This process included periodic site visits to evaluate the accuracy of the data; some data submissions were compared to that found in the UNOS database. In 2005–2006, 82.9% of post-transplant follow-up forms were submitted by the centers. In the follow-up period of greater than 2 years, 79.4% of forms were submitted from active centers.
As of June 1, 2006, 169 patients were registered with the diagnosis code of ‘autoimmune hepatitis/cirrhosis’ or ‘fulminant autoimmune hepatitis.’ Each center registering one or more of these patients was sent a supplemental form in order to confirm the diagnosis and obtain information on testing for the presence of serum auto-antibodies: nuclear (ANA), smooth muscle (ASM), liver-kidney microsomes (LKM-1), or ‘other antibodies’ defined as anti-liver cytosol-1 (LC-1), anti-asialoglycoprotein receptor or anti-soluble liver antigen. The form was completed for 132 patients of whom 2 were excluded (final diagnosis of primary sclerosing cholangitis; cirrhosis not considered to be of autoimmune origin). Of the 130 registered patients with a completed form, 17 were not yet transplanted, while 113 received a first liver-only transplant and form the patient population for this study. The age distribution of AIH patients compared with non-AIH patients (n=2178) is shown in figure 1. Certain outcomes in young infants differ from those in older children (14). Given that no AIH patient was under 1 year of age (compared to 35.2% of the whole SPLIT population), the AIH group was compared in this study to SPLIT patients that were older than one year of age (non-AIH group, n=1411).
Figure 1
Figure 1
Age distribution of AIH patients (n=113) and the total non-AIH population (n=2178), all recipients of a first liver-only transplant in SPLIT. Non-AIH patients >1 year were included in the study (n=1411) An external file that holds a picture, illustration, etc.
Object name is nihms257704ig1.jpg Non-AIH; An external file that holds a picture, illustration, etc.
Object name is nihms257704ig2.jpg AIH.
The pre-transplant diagnosis of AIH was in all cases accepted by pediatric hepatologists at SPLIT centers and reported to the SPLIT database. Although the definition of AIH, as with other primary diagnoses, is not operationalized in the SPLIT database, SPLIT centers constitute tertiary care institutions with specific expertise in pediatric hepatology who are currently active in transplanting children for AIH and other liver diseases within North America. Information was obtained from the registry on patient age, sex, ethnicity, blood group, fulminant vs. chronic presentation; calculated Pediatric End Stage Liver Disease (PELD) score, hospitalization status (at home, hospitalized, ICU), height and weight Z-scores, type of donor organ (cadaveric whole, reduced, split; living donor). Immunosuppression was recorded as initial and long-term (one month, 12 months and 2 years post-transplant). Outcomes included graft and patient survival; early acute rejection (<3 months), late acute rejection (>3 months), chronic and steroid resistant rejection. The diagnosis of rejection was made according to each individual center’s practice. Complications included biliary, vascular and infectious complications, glucose intolerance and re-transplantation AIH type 1 was defined by the presence of ANA and/or ASM while AIH type 2 was defined by the presence of anti-LKM-1 or anti-LC-1. Occasional patients with both ANA and LKM-1 were defined as AIH type 2. No data is available for studying disease recurrence and explant histology is not recorded in the database.
Statistical Analysis
Data are presented as percentage or mean ± standard error. Wilcoxon tests were used for testing the group differences of continuous variables. Large sample Chi-Square tests and Fisher’s exact tests were used to test the group differences of categorical variables. The Kaplan-Meier method was used to estimate the probability of time to event. Log-rank test was used for testing the group differences for the time to event data. Univariate Cox regression analysis was used to examine factors associated with patient and graft survival in AIH patients. Factors included liver disease presentation (fulminant vs. chronic); era of transplantation (1995–1999 vs. 2000–2006); height and weight deficit ( < 2 z-scores vs. > 2 z-scores); warm ischemia time; initial immunosuppression (cyclosporine A-based vs. tacrolimus-based); age at transplantation (1–5 years, 5–13 years, >13 years); organ type (living donor, cadaveric reduced, split, whole organ); donor age ( 0–6 months, 6–12 months, 18–50 years, >50 years). For multilevel categorical factors, the “overall p-value” indicates that the risk factor has an effect on the outcome. A statistically significant “overall p-value” indicates that at least two levels of the risk factor differ with respect to the outcome. Pairwise comparisons between two levels of interest of a risk factor were indicated by the “p-value”. Factors significant at 0.10 level in the univariate analysis were entered into a multivariate model. In addition, outcomes in AIH and non-AIH patients were compared for patient and graft survival and for rejection, adjusting for those factors of interest as defined in univariate analysis. All statistical analyses were implemented using the SAS System for Windows, version 9.1.3 (SAS Institute Inc., Cary, N.C.).
a) Patient Characteristics
The 113 AIH patients who received a first only liver transplant represented 4.9% of those transplanted within SPLIT. In examining the temporal distribution of AIH cases by year of listing (<2000, 2000–2002, 2003–2006) no difference in the proportion of AIH cases was observed (p=0.37). Characteristics at the time of transplant of the total AIH population and of subgroups with a chronic or fulminant presentation were compared with non-AIH patients (table 1). AIH patients were significantly older than non-AIH, and received a greater proportion of whole, deceased donor organ transplants (75.2% vs.59.3%, p=0.008), including few living donor organs (7.1% vs. 11.5%, p=0.008). AIH patients showed less impaired growth with a greater proportion of females and children of non-white ethnicity. In particular, a greater proportion of African-American and Latino-American patients were transplanted for AIH than for other diagnoses (49.6% AIH vs. 29.7% non-AIH, p<0.0001). No differences were observed between the groups for hospitalization status, for blood type or for median PELD score (9.6 vs.8.6).
Table 1
Table 1
Patient Characteristics and Outcome
b) Immunosuppression
The immunosuppressive regimen at transplant and throughout two years of follow-up is shown in table 2. At transplant, there were no differences between the groups in the use of induction therapy, corticosteroids, calcineurin inhibitors, azathioprine or sirolimus. By one month post-transplant, cyclosporine-based therapy was reduced in both groups in favor of tacrolimus and remained thereafter relatively unchanged until at least two years post-transplant. However, a greater reduction in the use of cyclosporine-based immunosuppression over time was observed in AIH patients (45.8% reduction, AIH vs. 16.1% reduction, non-AIH). By one to two years after liver transplant, monotherapy was more common in non-AIH patients due principally to greater reductions in the use of corticosteroids and azathioprine. MMF was used in a greater proportion of AIH patients than non-AIH from the time of transplantation; over time similar but small reductions in the use of MMF was reported in both groups. Sirolimus was introduced in a greater proportion of AIH patients beginning at one year after transplantation.
Table 2
Table 2
Type of Immunosuppression in AIH and Non-AIH Group
c) Outcome
The estimated probability of 5-year survival was 86% (95%CI 73–93). Univariate analysis did not identify any factor that was significantly associated with patient and graft survival in the AIH patients (table 3). Factors significant at a p-value of <0.1 in the univariate model were entered into a multivariate model. Variables selected for analysis of patient survival were liver disease presentation, weight deficit at transplant, and era of transplant; for graft survival analysis liver disease presentation and warm ischemia time were selected. Of these factors, only longer warm ischemia time was associated with a higher risk of graft loss (HR1.20; 95%CI 1.01–1.41, p=0.0374). When the AIH group was compared with the non-AIH group, no difference in patient or graft survival was observed (figure 2). Similarly, univariate analysis adjusting for various factors of interest revealed no significant differences between the AIH and non-AIH groups (table 4).
Table 3
Table 3
Univariate Analysis of Patient and Graft Survival for AIH Subjects
Figure 2
Figure 2
Kaplan-Meier curves for patient (A) and graft (B) survival in AIH and in Non-AIH patients > 1year of age.
Table 4
Table 4
Comparison of Patient Survival, Graft Survival and Rejection between AIH and Non-AIH groups
The time to first rejection is shown in figure 3, the curves remaining superimposed until after 6 months. No differences between AIH and non-AIH patients were observed for early acute rejection (31.9% vs. 31.3%), chronic rejection (3.5% vs. 3.0%) and steroid resistant rejection (12.4% vs. 9.0%). However, AIH patients were at greater risk of late acute rejection (28.3% vs. 21.1%, log-rank p=0.0056). In univariate analysis, there was no difference in risk of rejection between AIH and non-AIH groups (table 4).
Figure 3
Figure 3
Kaplan-Meier curves for first rejection in AIH and in Non- AIH patients > 1year of age.
d) Complications
No differences were observed between AIH and non-AIH patients within the first year pos-transplant for biliary tract complications (15.9% vs. 16.9%, p=0.783), for vascular complications (8.8% vs. 15.5 %, p=0.05), for glucose intolerance (12.4% vs. 10.5%, p=0.528) or for infection with cytomegalovirus (5.3 % vs. 8.6 %, p=0.218). Lymphoproliferative disease was rare in both groups (AIH n=0, non-AIH n=31 (2.2%)). This was associated with significantly fewer Epstein Barr virus (EBV) infections in AIH patients (n=1) than non-AIH n=95 (6.7%) log rank p value= 0.0185). Within the first month, fungal infections were similar but bacterial infections were less frequent in AIH patients (16.8% vs. 28.5%, p=0.013). Re-transplantation was required in 11 (9.7%) AIH patients and in 9.9% of non-AIH (ns); none was for recurrent disease: primary graft dysfunction (2); biliary complications (1); hepatic artery thrombosis (2); acute cellular rejection (2); chronic rejection (1); not reported (3).
e) Chronic vs. fulminant presentation of AIH
AIH patients were classified by transplant for complications of chronic disease (60%, n=68) or by fulminant presentation (40%, n=45). No significant differences were observed overall between chronic and fulminant presentation for age, ethnicity, weight, and blood type, degree of cholestasis, type of donor organ, hospitalization status or risk of for rejection. The calculated PELD of the chronic group was 10.8±1.7. A fulminant presentation was more common in males (52.5% vs. 47.5% chronic) than in females (32.8% vs. 67.2% chronic), p=0.042. Fulminant AIH patients had higher height z-scores. Cyclosporine appeared to be used less often for fulminant AIH but care is needed in interpreting these data as information was missing in 8/45 (17.8%) fulminant vs. 5/68 (7.4%) chronic. While no differences in 4 year patient or graft survival were observed, all deaths in the fulminant group (5/45) occurred within the first year (log rank test p<0.05).
AIH and non-AIH patients with a fulminant presentation were also compared (table 1). At transplant, fulminant non-AIH patients were younger and appeared more ill as suggested by a lower weight and a higher serum bilirubin and INR. Patient and graft survival in AIH fulminant patients was similar to the non-AIH fulminant and the chronic AIH group (table 1).
f) AIH type 1 vs. AIH type 2
Of the 113 AIH patients, 87 had serological data available; however for 13 of these cases the autoantibody data was incomplete (one or more antibody missing) thus preventing precise classification. Of the remaining 74 patients, 60 (81%) were AIH type 1, 9 (12%) were AIH type 2 and 5 (6.8%) were negative for all markers. No patients were reported with anti-asialoglycoprotein receptor or anti-soluble liver antigen antibodies. Table 5 shows the characteristics of these two subgroups. Overall the age at transplantation was similar for both AIH types. The two males with AIH type 2 were transplanted with a fulminant presentation; they were younger (7.8±6.5 years) than other males presenting with either chronic or fulminant AIH type 1 (13.4±1.2 years and 15.4±0.6 years respectively). All females were transplanted as adolescents, whether with a fulminant presentation (AIH type 1: 15.3± 0.8 years vs. AIH type 2: 14.9±0.1 years), or with chronic disease (AIH type 1: 12.3±0.8 vs. AIH type 2: 12.6±1.9 years). Due to the small numbers of AIH 2 patients, meaningful statistical comparisons could not be made.
Table 5
Table 5
Patient Characteristics and Outcome by AIH Subtype
Current understanding of the course of patients who receive a liver transplant for AIH is largely based on the adult literature and on pediatric series from individual centers. The patients herein described represent the largest group of children with AIH followed after liver transplantation. 4.9% of transplants within SPLIT were for AIH, a similar proportion to that reported in adults (4% European Liver Transplant Registry, 2006; 3.6% The Organ Procurement and Transplantation Network database, 2007). Most children in this study came to transplant with chronic disease. If one reasonably assumes that the 17 patients not yet transplanted of the 130 that were registered are likely to be listed with chronic disease, then 85 children with AIH (75%) would come to transplant with complications of cirrhosis. As such, strategies to reduce the need for transplantation in AIH would seem best targeted to reducing the progression of the disease to cirrhosis, including early detection, aggressive initial treatment and, at least in pediatrics, a very close surveillance of patients in whom weaning of therapy is considered. Given the nature of a registry it is difficult to determine the precise indications for listing these children for transplant (liver failure, complications of portal hypertension) but the mean PELD scores for those with a chronic presentation were under 15, suggesting that the majority of patients were not in advanced liver failure at the time of transplant.
Many of the demographic differences from the other children transplanted within SPLIT reflect the nature of AIH as a disease that affects older children with a female preponderance characterized by preserved growth, greater use of whole organs and fewer living donors. Of interest is the higher proportion of non-white children transplanted for AIH compared to other diagnoses, potentially indicating a more aggressive disease in some ethnic groups, as was previously suggested (15,16). Socioeconomic factors influencing access to timely evaluation and therapy could be a confounding factor that would require further verification (17). Children transplanted for AIH have excellent outcomes that are not different from children undergoing liver transplant for other conditions. Our results compare favorably with the 5-year patient survival of 0.79 (95%CI 0.51–0.92) recently reported for pediatric AIH patients in the European Liver Transplant Registry (18). However, AIH patients experience greater levels of immunosuppression in the first two years after transplant and are at higher risk of late, acute rejection but not of steroid-resistant rejection or chronic rejection. A greater proportion of AIH patients received corticosteroids and was converted to tacrolimus-based immunosuppression by the end of the first year post-transplant. We cannot readily distinguish between the administration of higher degrees of immunosuppression as a consequence of therapy for late rejection episodes (as suggested by the greater use of sirolimus by the end of the first year) and an aggressive immunosuppressive approach from the time of transplantation to address a perceived greater risk for rejection (as suggested by the greater use of MMF from the time of transplant).
Surprisingly, despite increased immunosuppression AIH patients experienced less infectious complications than non-AIH patients, perhaps related to their older age (more likely already exposed to CMV and EBV), lack of previous surgery and better nutritional status. AIH patients are at greater risk for type 1 diabetes. Given the preference for tacrolimus-based immunosuppression and the prolonged use of corticosteroids, one might expect to observe glucose intolerance more frequently but this was not observed. The rate of re-transplantation in this study was only 9.7% and none was for recurrent disease. Clear criteria for recurrent AIH were not available at the inception of the SPLIT database and still remain somewhat controversial. We were, therefore, unable to study the risk of relapse of AIH post-transplant which has been estimated at approximately 22% (19).
Of concern was the finding that 23% of children transplanted for AIH appear not to have had any search for confirmatory serum markers. While such markers are not pathognomonic for AIH, the absence of a systematic search for serologic markers hinders the study of the course of AIH before and after transplantation. This should be addressed by the pediatric transplant community.
Important research questions concerning children transplanted for AIH include the proportion of all AIH patients requiring transplant, the duration of disease before listing, the type of pre-transplant therapy, its duration and its impact (non-response versus an initial response followed by long-term deterioration). Post-transplant issues include the development of co-morbidities such as ulcerative colitis, how to identify recurrent disease and the impact of medication adherence on outcomes. These questions are not well answered by a pediatric transplant registry such as SPLIT, or by individual centers, but will require the cooperation in the form of an international registry of AIH.
In conclusion, the majority of children receiving a liver transplant for autoimmune hepatitis in North America are female adolescents with AIH type 1 presenting as chronic disease, with an over representation of African-Americans and Latino-Americans compared with the overall transplant population. Despite a greater degree of immunosuppression, outcomes are similar to the overall population with no increase in infectious or metabolic complications and although the risk of late acute cellular rejection is higher this does not result in increased chronic rejection, steroid-resistant rejection or need for re-transplantation.
Acknowledgments
The SPLIT Research Group are: S. Dunn, J. Menendez, L. Flynn (Alfred I Dupont Hospital for Children, Wilmington, DE); M. Jonas, D.. Healey. (Boston Children’s Hospital, Boston, MA); R. Kane, E. Phillips, H. Solomon(Cardinal Glennon Children’s Hospital, St. Louis University, St. Louis, MO); T. Heffron, S. Sekar, T. Pillen, L. Davis, J.DePaolo, G.Smallwood; (Children’s Healthcare of Atlanta, Atlanta, GA); J. Bucuvalas, F. Ryckman, A. Howkins, G. Arya, S. Krug, C. Tiao, K. Campbell.(Children’s Hospital Cincinnati, Cincinnati, OH); M. Narkewicz, R. Sokol, F. Karrer, K. Orban-Eller (Children’s Hospital Denver, University of Colorado School of Medicine, Denver, CO); E. Rand, K. Anderer, B. Patel(Children’s Hospital of Philadelphia, Philadelphia, PA); G. Mazariegos, N. Chien, MA Karuna, K Haberman (Children’s Hospital of Pittsburgh, Thomas E Starzl Transplantation Institute Pittsburgh, PA); P. Atkinson (Children’s Hospital Western Ontario, London, ON, Canada); G. Telega, S. Lerrett, J Nebel (Children’s Hospital of Wisconsin, Milwaukee, WI); D. Desai, N. Mittal, L. Cutright, L. Arnott (Children’s Medical Center of Dallas, Dallas, TX); E. Alonso, J. Lokar, S. Kelly, K. Neighbors, R Superina, P Whitington, K Tuzinkiewicz (Children’s Memorial Medical Center, Transplant Center of Excellence, Chicago, IL); W. Andrews, J. Daniel, V. Fioravanti, A. Tendick (Children’s Mercy Hospital, Kansas City, MO); S. Jarvis (Duke University Medical Center, Durham, NC); A. Fecteau, V. Ng, W Drew (Hospital for Sick Children Toronto, Toronto, ON, Canada); J. Tector, J. Lim, J. Molleston, J. Pearson, S Hicks (Indiana University Medical College, Indianapolis, IN); K. Schwarz, P. Colombani, M. Alford, C Bhave, L Wilson, R. Jurao (Johns Hopkins Hospital, Baltimore, MD); J. Eason, J. Eshun, S. Powell, H Grewl (Le Bonheur Children’s Medical Center, Memphis, TN); D. Freese, M El-Yossef, J. Weckwerth, J. Greseth, L Pearson, L. Young (Mayo Medical School, Rochester, MN); R. Fisher, M. Akyeampong, M. Benka, A. Lassiter (Medical College of Virginia, Richmond, VA); N. Sekar, S. Parkar, R. Gagliardi (Mount Sinai Medical Center, New York, NY); S. Lobritto, J Cho (New York Presbyterian Hospital, New York, NY); L. Book, M. O’Gorman, C. Kawai, L. Bruschke, J. Kraus, R. Thorson(Primary Children’s Hospital Medical Center, Salt Lake City, UT); C. Viau (Sainte-Justine Hospital, Montreal, QC, Canada); R. Shepherd, J. Lowell, M. Nadler, S. Guelker (St. Louis Children’s Hospital, St. Louis, MO); W. Berquest, M. Castillo, A. Bula, R. Berquist (Stanford University Medical Center, Palo Alto, CA);
P. Karpen, J. Mayo, J. Goss, D. Ybarra, B. Carter, (Texas Children’s Hospital, Houston, TX); S. McDiarmid, S. Fiest (UCLA Medical Center, Los Angeles, CA); S. Gilmour, B. Dodd, N. Kneteman, A. Jones (University of Alberta, Edmonton, AB, Canada); J. Lavine, A. Khanna, R. Clawson (University of California San Diego, San Diego Medical Center, San Diego, CA); P. Rosenthal, D. Filipowski, J. Roberts (University of California San Francisco, San Francisco, CA); J. Millis, P. Boone (University of Chicago, Chicago, IL); R. González-Peralta, M. Langham, M. Hodik, (University of Florida-Shands Children’s Hospital, Gainesville, FL); A. Tzakis, T. Kato, D. Weppler, L. Cooper, M. Gonzalez, L. Smith, A. Santiago (University of Miami, Jackson Memorial Hospital, Miami, FL); J. Lopez, J. Magee, V. Shieck (University of Michigan, Ann Arbor, MI); A. Humar, B. Durand. (University of Minnesota, Minneapolis, MN); A. Langnas, D. Antonson, J. Botha, W. Grant, D. Sundan, D. Andersen, B. Fleckten, K. Seipel, C. Torres, B. Shaw. (University of Nebraska Med Center, Omaha, NE); J. Fair, P. McIver, J. Young, A. Raizada, J. Prinzhorn, . (University of North Carolina, Chapel Hill, NC); M. Orloff, T. Shisler, T. Rossi, C. Hill-Sober. (University of Rochester, Strong Memorial Hospital, Rochester, NY); G. Halff, J. Silva (University of Texas, HSC San Antonia, San Antonio, TX); S. Horslen, K. Wallace. (University of Washington Seattle, Seattle, WA); M. Kalayoglu, A. D’Alessandro,, R. Judd, S. Knechtle, E. Spaith (University of Wisconsin, Madison, WI).
The Studies of Pediatric Liver Transplantation (SPLIT) research group thanks the following people at the data coordinating center (EMMES Corporation): A. Lindblad PhD, K. Martz, D. Falleroni, J. He, G. Fraser, J. Mitchell, L.Covington, N. Hornbeak, N. Patel.
Abbreviations
SPLITStudies of Pediatric Liver Transplantation
AIHAutoimmune Hepatitis
PELDPediatric end stage liver disease
UNOSUnited Network for Organ Sharing
ANAanti-nuclear antibody
ASManti-smooth muscle antibody
LKM-1anti-liver kidney microsomal type 1 antibody
LC1anti-liver cytosol antibody
MMFmycophenolate mofetil

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