Eur J Pediatr Surg 2012; 22(01): 060-066
DOI: 10.1055/s-0031-1291288
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Liver Transplantation in Children with Cystic Fibrosis: Experience in our Centre and Preliminary Results with a Combined En Bloc Liver-Pancreas Graft

M. Miguel
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
A.M. Andres
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
M. Lopez-Santamaria
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
S. Barrena
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
L. Hierro
2   Hospital Universitario La Paz, Servicio de Hepatología Infantily Trasplante Hepático Infantil, Madrid, Spain
,
F. Hernandez
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
M. Ramírez
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
E. Frauca
2   Hospital Universitario La Paz, Servicio de Hepatología Infantily Trasplante Hepático Infantil, Madrid, Spain
,
J.L. Encinas
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
S. Lopez-Fernandez
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
,
P. Jara
2   Hospital Universitario La Paz, Servicio de Hepatología Infantily Trasplante Hepático Infantil, Madrid, Spain
,
J.A. Tovar
1   Hospital Universitario La Paz, Pediatric Surgery, Madrid, Spain
› Author Affiliations
Further Information

Publication History

16 May 2011

21 September 2011

Publication Date:
07 December 2011 (online)

Abstract

Aim of the study Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: 1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; 2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT).

Methods 9 children (6M/3F) with CF and ESLD underwent LT between 1993 and 2010; median age and weight were 12.3 years (range: 5.4–17.0) and 36.7 kg (range: 14.2–58.5), respectively. 4 patients received a whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT. Immunosuppression followed the protocols at the time of transplantation.

Results Liver function was restored in all patients and none of them needed re-transplantation. Median follow-up was 105 months (range: 4–206). 1 child died of respiratory failure at 23 months after transplantation while awaiting pulmonary transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children already had IDD before transplantation and 3 developed diabetes immediately after transplantation. 2 had not developed IDD at the end of the study: the youngest at the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and who recovered normal exocrine and endocrine pancreatic function after transplantation.

Conclusions LT is a realistic option to treat CF-related ESLD children. IDD is common in these patients. En bloc liver-pancreas transplantation is an appealing option, since it simultaneously restores exocrine function and prevents IDD. This procedure has clear technical advantages over simultaneous isolated liver and pancreas transplantation.

 
  • References

  • 1 Colombo C, Battezzati PM, Crosignani A , et al. Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome. Hepatology 2002; 36 (06) 1374-1382
  • 2 Herrmann U, Dockter G, Lammert F. Cystic fibrosis-associated liver disease. Best Pract Res Clin Gastroenterol 2010; 24 (05) 585-592
  • 3 Costa M, Potvin S, Berthiaume Y , et al. Diabetes: a major co-morbidity of cystic fibrosis. Diabetes Metab 2005; 31: 221-232
  • 4 Marchetti P. New-onset diabetes after liver transplantation: from pathogenesis to management. Liver Transpl 2005; 11 (06) 612-620
  • 5 Koch C, Rainisio M, Madessani U , et al. Presence of cystic fibrosis-related diabetes mellitus is tightly linked to poor lung function in patients with cystic fibrosis: data from the European Epidemiologic Registry of Cystic Fibrosis. Pediatr Pulmonol 2001; 32 (05) 343-350
  • 6 Starzl TE, Todo S, Tzakis A , et al. Abdominal organ cluster transplantation for the treatment of upper abdominal malignancies. Ann Surg. 1989; 210 (03) 374-385 , discussion 385–386
  • 7 Parkins MD, Parkins VM, Rendall JC , et al. Changing epidemiology and clinical issues arising in an ageing cystic fibrosis population. Ther Adv Respir Dis 2011; 5 (02) 105-119
  • 8 Fridell JA, Bond GJ, Mazariegos GV , et al. Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center's experience. J Pediatr Surg 2003; 38 (08) 1152-1156
  • 9 Mekeel KL, Langham Jr MR, Gonzalez-Perralta R , et al. Combined en bloc liver pancreas transplantation for children with CF. Liver Transpl 2007; 13 (03) 406-409
  • 10 Milkiewicz P, Skiba G, Kelly D , et al. Transplantation for cystic fibrosis: outcome following early liver transplantation. J Gastroenterol Hepatol 2002; 17 (02) 208-213
  • 11 Kuo HT, Lau C, Sampaio MS , et al. Pretransplant risk factors for new-onset diabetes mellitus after transplant in pediatric liver transplant recipients. Liver Transpl 2010; 16 (11) 1249-1256
  • 12 Rosenecker J, Höfler R, Steinkamp G , et al. Diabetes mellitus in patients with cystic fibrosis: the impact of diabetes mellitus on pulmonary function and clinical outcome. Eur J Med Res 2001; 6 (08) 345-350
  • 13 Moran A, Hardin D, Rodman D , et al. Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res Clin Pract 1999; 45 (01) 61-73
  • 14 Fioretto P, Steffes MW, Sutherland DE , et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339 (02) 69-75
  • 15 Krimsky WS, Parker HW. Update: epidemiology of cystic fibrosis. Curr Opin Pulm Med 2002; 8 (06) 552-553
  • 16 Mieles L, Todo S, Tzakis A , et al. Treatment of upper abdominal malignancies with organ cluster procedures. Clin Transplant 1990; 4: 63-67
  • 17 Stern RC, Mayes JT, Weber Jr FL , et al. Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient. Clin Transplant 1994; 8 (01) 1-4
  • 18 Fridell JA, Vianna R, Kwo PY , et al. Simultaneous liver and pancreas transplantation in patients with cystic fibrosis. Transplant Proc 2005; 37 (08) 3567-3569
  • 19 Trotter JF, Bak TE, Wachs ME , et al. Combined liver-pancreas transplantation in a patient with primary sclerosing cholangitis and insulin-dependent diabetes mellitus. Transplantation 2000; 70 (10) 1469-1471
  • 20 Gaber AO, Shokouh-Amiri H, Hathaway DK , et al. Pancreas transplantation with portal venous and enteric drainage eliminates hyperinsulinemia and reduces postoperative complications. Transplant Proc 1993; 25: 1176-1178
  • 21 Pirenne J, Nakhleh RE, Dunn DL. Graft-versus-host disease after multiorgan transplantation. J Surg Res 1991; 50 (06) 622-628
  • 22 Wang C, Sun J, Li L , et al. Combined liver and pancreas transplantation induces pancreas allograft tolerance. Transplant Proc 1197 29: 1145-1146