"To understand organ transplantation is to understand all of modern
medicine, and to practice organ transplantation is to comprehend
the fundamental challenges of advanced healthcare delivery in
general. "
"The most fundamental diagnosis of medicine: alive or dead?"
Allan D. Kirk Duke University Medical Center, Durham, NC, USA
Organ transplantation (OTx) represents the only curative treatment for end-stage liver, heart, and lung diseases but it may also represent a lifesaving option following failure of other organs. Although end-stage kidney disease patients can be effectively treated with renal replacement therapy (like hemodialysis), kidney transplantation (KT) is generally accepted as the best treatment for both quality of life and cost effectiveness in the great majority of those with end-stage kidney disease. The failure of the endocrine pancreas, with consequent diabetes mellitus, is generally treated by insulin therapy; however, some patients with hypoglycemia unawareness and brittle diabetes may benefit from pancreas transplantation. In the same way, the standard treatment for patients with intestinal failure is parenteral nutrition. However, for those patients who develop life-threatening complications such as recurrent infections, thrombosis/blockage of major blood vessels, and intestinal failure-associated liver disease, bowel transplantation is a lifesaving option. The road to successful organ grafting in humans has been long and fraught with problems. Over the past half century, there have been major advances in the field of transplantation including improved surgical techniques, anesthesia, microbiology, interventional radiology,immunosuppression (IS), and per/post-operative care. All these elements have substantially improved patient and graft survival (particularly for kidney and liver transplantation) although outcomes for both intestinal and pancreas transplantation are still poor (Table 2.1). However, this success is only partial: long-term survival of patients is reduced compared with age- and sex-matched controls; and the shortage of organs compared with need, which translates in the mortality of those who do not receive the organ. Kidney transplant (KT) has improved both short and long-term survival, although there are remarkable disparities between countries [1]. Risk-adjusted survival after liver transplantation (LT) has improved primarily because of a reduction in early/postoperative deaths. Adult liver recipients who survive the first postoperative year have an estimated 7.7-year reduction in life expectancy compared with an age- and sex-matched population. The extent of reduced life expectancy in LT depends on several factors, including recipient’s age, gender, and indication [2]. Patient and graft survival after OTx is limited by many factors, including the recurrence of the original disease: this includes not only malignancy but also viral infections (like hepatitis C) after LT and recurrence of autoimmune diseases leading to graft failure (such as recurrent glomerular disease in KT or autoimmune hepatitis in LT). Furthermore, the consequences of long-term IS may limit survival
*
"Solid Organ Transplantation: Has the Promise Been Kept and the Needs Met? Marco Carbonea,b and James M. Neubergerb,c a Liver Unit, Addenbrooke’s Hospital, Cambridge, UK, b Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, c Liver Unit, Queen Elizabeth Hospital, Birmingham, UK"
"The most fundamental diagnosis of medicine: alive or dead?"
Allan D. Kirk Duke University Medical Center, Durham, NC, USA
Organ transplantation (OTx) represents the only curative treatment for end-stage liver, heart, and lung diseases but it may also represent a lifesaving option following failure of other organs. Although end-stage kidney disease patients can be effectively treated with renal replacement therapy (like hemodialysis), kidney transplantation (KT) is generally accepted as the best treatment for both quality of life and cost effectiveness in the great majority of those with end-stage kidney disease. The failure of the endocrine pancreas, with consequent diabetes mellitus, is generally treated by insulin therapy; however, some patients with hypoglycemia unawareness and brittle diabetes may benefit from pancreas transplantation. In the same way, the standard treatment for patients with intestinal failure is parenteral nutrition. However, for those patients who develop life-threatening complications such as recurrent infections, thrombosis/blockage of major blood vessels, and intestinal failure-associated liver disease, bowel transplantation is a lifesaving option. The road to successful organ grafting in humans has been long and fraught with problems. Over the past half century, there have been major advances in the field of transplantation including improved surgical techniques, anesthesia, microbiology, interventional radiology,immunosuppression (IS), and per/post-operative care. All these elements have substantially improved patient and graft survival (particularly for kidney and liver transplantation) although outcomes for both intestinal and pancreas transplantation are still poor (Table 2.1). However, this success is only partial: long-term survival of patients is reduced compared with age- and sex-matched controls; and the shortage of organs compared with need, which translates in the mortality of those who do not receive the organ. Kidney transplant (KT) has improved both short and long-term survival, although there are remarkable disparities between countries [1]. Risk-adjusted survival after liver transplantation (LT) has improved primarily because of a reduction in early/postoperative deaths. Adult liver recipients who survive the first postoperative year have an estimated 7.7-year reduction in life expectancy compared with an age- and sex-matched population. The extent of reduced life expectancy in LT depends on several factors, including recipient’s age, gender, and indication [2]. Patient and graft survival after OTx is limited by many factors, including the recurrence of the original disease: this includes not only malignancy but also viral infections (like hepatitis C) after LT and recurrence of autoimmune diseases leading to graft failure (such as recurrent glomerular disease in KT or autoimmune hepatitis in LT). Furthermore, the consequences of long-term IS may limit survival
TABLE-2.1-Patient-Survival-after-Adult-Transplant-fromDBD-(20042006)
%-Patient-Survival-(95%-Confidence-Interval)
One-Year-Five-Years
Kidney-97/90
Liver-89-/77-
Heart-82/72
Lungs-77/54
Pancreas-98/94
Intestine-75
DBD,-donor-after-brain-death.
Data-from-transplant-Activity-Report-20112012—organ-donation-and
*
"Solid Organ Transplantation: Has the Promise Been Kept and the Needs Met? Marco Carbonea,b and James M. Neubergerb,c a Liver Unit, Addenbrooke’s Hospital, Cambridge, UK, b Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, c Liver Unit, Queen Elizabeth Hospital, Birmingham, UK"
ABBREVIATIONS
ALG anti-lymphocyte globulin
ATG antithymocyte globulin
BAFF B-cell-activating factor
CNI calcineurin inhibitor
DBD donation after brain death
DDLT deceased donor liver transplant
DGF delayed graft function
DRI donor risk index
EMEA European medicines evaluation agency
FDA food and drug administration
GVHD graft-versus-host disease
HCV hepatitis C virus
HLA human leukocyte antigen
ICOS inducible costimulator
IFN Interferon
IL interleukin
IS immunosuppression
JAK Janus kinase
KT kidney transplantation
LDLT living donor liver transplantation
LFT liver function test
MELD model for end-stage liver disease
OTx organ transplantation
mTOR mammalian target of rapamycin
SOT spontaneous operational tolerance
PNF primary nonfunction
TPN total parenteral nutrition
UKELD UK End-Stage Liver Disease
UNOS United Network for Organ Sharing
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