Cystic fibrosis (CF), an autosomal recessive genetic disorder of electrolyte transport in epithelial cells, affects multiple organs.  Lung transplantation is the most common transplant performed in CF patients, followed by liver transplantation alone and combined lung-liver transplantation in those with CF-associated liver disease (CFLD) . Several reports highlight the potential benefits of pancreas transplantation in CF-related diabetes (CFRD); however, it remains rare with only 28 transplants documented in the United States between 1987 and 2014.  Most pancreas transplants for CFRD have been performed in combination with a liver or lung transplant. 
Aim: Herein, we report the indications and clinical course of a successful combined lung, liver, and pancreas transplant. Methods and Results: The patient is a 19-year-old male who has the homozygous Delta F508 mutation in the CF transmembrane conductance regulator (CFTR) gene. During the two years prior to transplantation, pulmonary function declined significantly, bleeding from esophageal variceal bleeding developed, and he became insulin-dependent.  Following bilateral lung transplantation, the liver and pancreas were transplanted en bloc and the donor duodenum was drained into the recipient jejunum.  All organs functioned well immediately after transplantation. His post-operative course was complicated by the development of mild graft pancreatitis, non-occlusive thrombosis in the aortic conduit supplying the liver/pancreas graft, and stenosis of the right bronchial anastomosis, which required periodic balloon dilatation. At 1-year follow-up, FEV1 was 2.7 liters (64% of predicted); serum bilirubin, liver enzymes, albumin, and INR were in the normal range; he had gained 10 kg of weight without oral exocrine enzyme and vitamin supplements, and was insulin-independent.  His renal function was normal with an estimated glomerular filtration rate >120 ml/s. Serum vitamin A, D, E levels at 1-year were normal.  At 1-year, fasting blood glucose (BG) and HBA1c values were 5.4 mmol/L and 0.058, respectively.  Oral glucose tolerance testing at 1-year showed BG values of 5.4 mmol/L and 10.0 mmol/L at 0 and 2 hours, respectively; the corresponding C-peptide values were 725 pmol/L and 2436 pmol/L.  
Conclusion: combined lung-liver-pancreas transplantation is an attractive option in selected CF patients.  The incidence of de novo diabetes after isolated lung and liver transplantation alone exceeds 50%, suggesting that pancreas transplantation might be more broadly considered in CF patients with glucose intolerance, which will result in better quality of life and possibly survival.