Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years’ experience from the Nordic countries
Corresponding Author
S. Malenicka
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Correspondence
Silvia Malenicka, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Email: [email protected]
Search for more papers by this authorB.-G. Ericzon
Division of Transplantation Surgery, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Search for more papers by this authorM. H. Jørgensen
Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorH. Isoniemi
Department of Transplantation Surgery, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorT. H. Karlsen
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Search for more papers by this authorM. Krantz
Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Queen Silvia Children's Hospital, Gothenburg, Sweden
Search for more papers by this authorM. Olausson
Department of Transplantation Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for more papers by this authorA. Rasmussen
Department of Transplantation Surgery, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorK. Rönnholm
Department of Pediatric Nephrology, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorT. Sanengen
Department of Pediatric Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Search for more papers by this authorT. Scholz
Department of Transplantation Surgery, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorB. Fischler
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Contributed equally.Search for more papers by this authorA. Nemeth
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Contributed equally.Search for more papers by this authorCorresponding Author
S. Malenicka
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Correspondence
Silvia Malenicka, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Email: [email protected]
Search for more papers by this authorB.-G. Ericzon
Division of Transplantation Surgery, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Search for more papers by this authorM. H. Jørgensen
Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorH. Isoniemi
Department of Transplantation Surgery, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorT. H. Karlsen
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Search for more papers by this authorM. Krantz
Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Queen Silvia Children's Hospital, Gothenburg, Sweden
Search for more papers by this authorM. Olausson
Department of Transplantation Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for more papers by this authorA. Rasmussen
Department of Transplantation Surgery, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorK. Rönnholm
Department of Pediatric Nephrology, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorT. Sanengen
Department of Pediatric Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Search for more papers by this authorT. Scholz
Department of Transplantation Surgery, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorB. Fischler
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Contributed equally.Search for more papers by this authorA. Nemeth
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
Contributed equally.Search for more papers by this authorAbstract
Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 μmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the “sickest children first” allocation policy and correction of malnutrition before surgery.
References
- 1Martin SR, Atkinson P, Anand R, Lindblad AS. Studies of pediatric liver transplantation 2002: patient and graft survival and rejection in pediatric recipients of a first liver transplant in the United States and Canada. Pediatr Transplant. 2004; 8: 273–283.
- 2 US Transplant, Scientific Registry of Transplant Recipients. Available at www.srtr.org.
- 3Goss JA, Shackleton CR, McDiarmid SV, et al. Long-term results of pediatric liver transplantation: analysis of 569 transplants. Ann Surg. 1998; 228: 411–420.
- 4Caccioarelli TV, Dvorchik I, Mazariegos GV, et al. An analysis of pretransplantation variables associated with long-term allograft outcome in pediatric liver transplant recipients receiving primary tacrolimus (FK 506) therapy. Transplantation. 1999; 68: 650–655.
- 5Wallot MA, Mathot M, Janssen M, et al. Long-term survival and late graft loss in pediatric liver transplant recipients: a 15-year single-center experience. Liver Transpl. 2002; 8: 615–622.
- 6Broering DC, Kim JS, Mueller T, et al. One hundred thirty two consecutive pediatric liver transplants without hospital mortality: lessons learned and outlook for the future. Ann Surg. 2004; 240: 1002–1012.
- 7Utterson EC, Shepard RW, Sokol RJ, Bucuvalas J, Magee JC, McDiarmid SV, Anand R; SPLIT Research Group. Biliary atresia: clinical profiles, risk factors, and outcomes of 755 patients listed for liver transplantation. J Pediatr. 2005; 147: 180–185.
- 8 United Networks for Organ Sharing. Available at www.unos.org.
- 9 Scandiatransplant. Available at www.scandiatransplant.org.
- 10 Annual Report NLTR 2011. Available at www.scandiatransplant.org.
- 11Buusuttil RW, Seu P, Millis JM, et al. Liver transplantation in children. Ann Surg. 1991; 213: 48–57.
- 12Adam R, Karam V, Delvart V, et al. ; All contributing centers (www.eltr.org); European Liver and Intestine Association (ELITA). Evaluation of indications and results of liver transplantation in Europe: a report from the European Liver Transplant Registry. J Hepatol. 2012; 57: 675–688.
- 13Roberts EA. Biliary atresia. The jaundiced baby. In: Disease of the Liver and Biliary System in Children, 3rd edn. Wiley-Blackwell; 2008:69.
- 14Chardot C, Buet C, Serinet MO, et al. Improving outcomes of biliary atresia: French national series 1986–2009. J Hepatol. 2013; 58: 1209–1217.
- 15Gu YH, Yokoyama K, Mizuta K, et al. Stool color card screening for early detection of biliary atresia and long-term native liver survival: a 19-year cohort study in Japan. J Pediatr. 2015; 166: 897–902.
- 16 Unit conversion. Available at www.dialysis-diagnostics.com.
- 17 Unit conversion. Available at http://www.endmemo.com/medical/unitconvert/Albumin.php.
- 18 PELD and MELD calculator. Available at http://optn.transplant.hrsa.gov/resources/allocationcalculators.asp?index=97.
- 19 Unit conversion. Available at http://www.endmemo.com/medical/unitconvert/Bilirubin.php.
- 20 Unit conversion. Available at http://www.endmemo.com/medical/unitconvert/Creatinine.php.
- 21Kamath BM, Rand EB. Evaluation of the candidate. Goals of evaluation. In: Pediatric Solid Organ Transplantation, 2nd edn. Blackwell Publishing Ltd; 2007: 207.
- 22Ling SC, Walters T, McKiernan PJ, Schwarz KB, Garcia-Tsao G, Shneider BL. Primary prophylaxis of variceal hemorrhage in children with portal hypertension: a framework for future research. J Pediatr Gastroenterol Nutr. 2011; 52: 254–261.
- 23Spada M, Gridelli B, Colledan M, et al. Extensive use of split liver for pediatric liver transplantation: a single-center experience. Liver Transplant. 2000; 6: 415–428.
- 24Testa G, Malago M, Broelsch CE. From living related to in-situ split liver transplantation: how to reduce waiting-list mortality. Pediatr Transplant. 2001; 5: 16–20.
- 25Arnon R, Annunziato RA, D′Amelio G, Chu J, Shneider BL. Liver transplantation for biliary atresia: is there a difference in the outcome for infants? J Pediatr Gastroenterol Nutr. 2016; 62: 220–225.
- 26Arnon R, Annunziato R, Miloh T, et al. Liver transplantation in children weighing 5 kg or less: analysis of the UNOS database. Pediatr Transplant. 2011; 15: 650–658.
- 27Shneider BL, Mazariegos GV. Biliary atresia: a transplant perspective. Liver Transplant. 2007; 13: 1482–1495.
- 28DeRusso PA, Ye W, Shepard R, et al. Growth failure and outcomes in infants with biliary atresia: a report from Biliary Atresia Research Consortium. Hepatology. 2007; 46: 1632–1638.
- 29Magnusson M, Fischler B, Svensson J, Petrini P, Schulman S, Nemeth A. Bile acids and coagulation factors: paradoxal association in children with chronic liver disease. Eur J Gastroenterol Hepatol. 2013; 25: 152–158.
- 30Chung P, Wong K, Tam P. Liver transplant for biliary atresia is associated with worse outcome – myth or fact? J Pediatr Surg. 2015; 50: 2134–2136.
- 31Cowles RA, Lobritto SJ, Ventura KA, et al. Timing of liver transplantation in biliary atresia – results in 71 children managed by multidisciplinary team. J Pediatr Surg. 2008; 43: 1605–1609.
- 32Singal AK, Kamath PS. Model for end-stage liver disease. J Clin Exp Hepatol. 2013; 3: 50–60.
- 33Herden U, Grabhorn E, Briem-Richter A, Ganschow R, Nashan B, Fischer L. Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant. Clin Transplant. 2014; 28: 1061–1068.
- 34Pestana RC, Baracat EI, Massarollo PC, Pereira LA, Szutan LA. Consequences of the implementation of the model of end-stage liver disease system for liver allocation in Brazil. Transplant Proc. 2013; 45: 2111–2114.
- 35Melcher ML, Roberts JP. Outcomes and risk factors. In: Pediatric Solid Organ Transplantation, 2nd edn. Blackwell Publishing Ltd; 2007:242.
Citing Literature
