|Year : 2019 | Volume
| Issue : 2 | Page : 78-81
Transplantation review: Liver, kidney, and pancreas transplantation
Department of HPB and Transplant Surgery, Fortis Hospital, Mumbai, Maharashtra, India
|Date of Submission||17-Oct-2019|
|Date of Acceptance||17-Oct-2019|
|Date of Web Publication||22-Nov-2019|
Dr. Rakesh Rai
Department of HPB and Transplant Surgery, Fortis Hospital, Mulund (West), Mumbai - 400 078, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rai R. Transplantation review: Liver, kidney, and pancreas transplantation. Biomed Res J 2019;6:78-81
In 1954, a kidney transplant was performed by Joseph Murray, J. Hartwell Harrison, John P. Merrill, and others. The procedure was done between identical twins Ronald and Richard Herrick which reduced problems of an immune reaction. The graft lasted for 8 years and Dr. Murray for his transplant-related work received Nobel prize in medicine in 1990.
Since that time, solid-organ transplantation has come a long way, and now for many patients with organ failure, transplantation has become the treatment of choice. These days transplantation of the heart, lung, liver, kidney, pancreas, and small bowel has become a routine procedure in the developed world. In India as well, transplantation of these organs is carried out in selected centers.
The source of graft for organ transplants come from either living donors as may be in the kidney, liver, and rarely, in pancreas transplants or from brain dead donors called donation after brain death (DBD). In case of heart and lung transplants, graft always comes from DBD donors. In Western world, majority of transplants are carried out using DBD donors. In India, due to the scarcity of DBD donors, majority of transplants are carried out using living donor grafts.
| Donation After Brain Death|| |
This type of donation is also called cadaveric organ donation. The word “Brain death” is a state of cessation of cerebral function, wherein the proximate cause is known and is considered irreversible. The American Association of Neurology has defined brain death with three cardinal signs, cessation of the functions of the brain, including the brainstem, coma or unresponsiveness, and apnea.
In India, the Transplantation of Human Organ Bill was introduced in the Lok Sabha on August 20, 1992, and became the Transplantation of Human Organ Act in 1994. Since 1995, organ transplants in India are being done using DBD donors.
Here, we will discuss about transplantation of the liver, kidney, and pancreas. Most commonly transplanted organs are liver and kidney.
| Kidney Transplant|| |
Living-donor kidney transplant is happening for more than 40 years. The cadaveric transplant started in 1995. At present, the Indian renal transplant program is the second largest program in numbers after the USA.
The indication of kidney transplantation is end-stage renal disease (ESRD), when glomerular filtration rate is <15 cc/min/1.73 m 2. The only option for long-term survival is either dialysis or renal transplantation. Common causes of ESRD are hypertension, diabetes, and autoimmune conditions. However, there are other genetic conditions and inborn error of metabolism that can also lead to ESRD. For majority of patients with ESRD, renal transplant is the treatment of choice, but unfortunately, most adult patients with ESRD are never referred for evaluation for transplantation and have 70% 5-year mortality on dialysis.
The prevalence of ESRD requiring transplantation in India is estimated to be between 151 and 232/million population. If an average of these figures is taken, it is estimated that almost 220,000 people require kidney transplantation in India. Against this, currently, approximately 7500 kidney transplantations are performed at 250 kidney transplant centers in India. Of these, 90% come from living donors and 10% from deceased donors. In living-donor renal transplant, any person can donate one of his kidney for transplantation. There are criteria to select a donor, but the intent of donation has to be altruistic.
Results of kidney transplant
The prognosis after kidney transplantation is generally excellent, with 1-year graft survival rates ranging from 93% to 98% and 5-year survival rates from 83% to 92% as shown in [Figure 1].
|Figure 1: Graft survival among adult kidney recipients as per age (OPTN/SRTR 2017 annual data report: Kidney)|
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Many factors influence the anticipated outcome. Human leukocyte antigen-identical transplants from living-related donors have the best overall graft survival rate, whereas transplants from complete-mismatch cadaveric donors have the worst. Other factors which affect transplant outcome are age of the donor, cold ischemia, and warm ischemia time.
Patients need to take immunosuppressive therapy lifelong after transplantation. These immunosuppressive medications decrease the chance of rejection of the graft.
| Liver Transplant|| |
The liver is the second most commonly transplanted major organ, after the kidney. In India, the first liver transplant was done in 1995 using a DBD graft, and the first living-donor liver transplant (LDLT) was done in 1998. Since then, number of liver transplants has increased rapidly, and many centers all over the country have started liver transplant programs. In 2014, close to 1400 liver transplants were done. Out of all the transplants, almost 85% are cadaveric and 15% LDLT. Centers in North India mainly do LDLT and centers in Mumbai and in South India do both cadaveric and LDLT. This is because cadaveric donation has not picked up in North India.
India has now emerged as the regional transplant center for southeast Asia. About 25%–30% of the total transplants per year are performed on patients from other countries. The foreign patients are transplanted using living donors who are patient's relatives.
Most common reason for liver transplant is a patient with cirrhosis which is a chronic liver disease with irreversible liver injury. There are many conditions which can cause progressive liver injury over many years leading to cirrhosis. The common conditions are alcoholic liver disease; nonalcoholic steatohepatitis; Viral hepatitis B and C viruses; autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, metabolic liver disease (alpha-1-antitrypsin deficiency, Wilson disease, tyrosinemia, glycogen storage disorder type I or type IV); and Budd–Chiari syndrome.
Then, there are patients who develop acute liver failure and may need liver transplantation. In acute liver failure, the disease causes liver damage within weeks to months. The common conditions leading to acute liver failure in India are – Hepatitis A, Hepatitis E infection, drug overdose like paracetamol poisoning, and acute Wilson disease. Patients with acute liver failure may not survive long and may need urgent liver transplant. To select patients who need urgent transplantation, there are selection criteria. One of the criteria which is used most commonly worldwide is King's College Criteria. Patients who fulfill the criteria are listed for urgent transplantation.
There are certain patients with liver cancer, mainly hepatocellular cancer, who can also benefit from liver transplant. The patients who need liver transplant but can wait are listed on the waiting list. In most countries, patients with more severe disease conditions are given priority. To assess disease severity, certain scores have been validated. The most common score is model for end-stage liver disease scoring system if they are more than 12 years or older, or the pediatric end-stage liver disease scoring system if they are younger than 12 years.
Source of graft
Like in kidney transplant, the liver graft can come from brain dead donors (DBD) or living persons. In case of DBD grafts, usually whole liver graft is used, but in certain situation, a full liver graft can be split into two separate grafts. This technique of splitting the graft can be very useful as there is severe shortage of organs.
A living altruistic donor can donate part of his liver. In certain countries like Korea and Japan, the DBD is very limited in number due to cultural and religious belief, so LDLT is the way for majority of patients. The living donor is an adult with matching blood group, although now blood group incompatible transplants are being done in certain centers. The living donor undergoes thorough investigations to assess his fitness for donation surgery as well as assessment of his liver function, anatomy, and liver volume.
| Results|| |
LT is a standard-proven therapy for ESLD and should be offered to any patient who needs it. Careful selection of both donors and recipients maximizes usage by optimizing outcomes. The graft and patient survival for 1 year are close to 90% and for 5 years up to 75%. The result of the transplant depends on many factors including the etiology of liver disease. [Figure 2] reflects the result of liver transplant as per etiology of the liver disease. This is from the scientific registry of transplant patients maintained by the US Department of Health. The risk to a living liver donor is 1 in 250 risks of mortality.
|Figure 2: Five-year patient survival postliver transplant as per liver disease|
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Posttransplant quality of life
Liver transplant patients remain on immunosuppressive therapy for life long, although the dose of medication required after 1 year of transplant is usually one tablet daily. Most of the recipients will go back to a productive life and with proper motivation; they can do whatever they want. There are examples of international sportspersons who have competed at international level after liver transplant.
| Pancreas Transplant|| |
The main purpose of pancreas transplantation is to ameliorate type 1 diabetes mellitus and produce complete independence from injected insulin. In addition, however, pancreas transplantation in patients with type 2 diabetes has increased steadily in recent years. With improvement in insulin delivery technology, the rate of pancreas transplant has decreased all over the world [Figure 3].
|Figure 3: Five-year patient survival following different types of pancreas transplant|
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The most common indication for pancreas transplant is a patient with juvenile type 1 diabetes who at young age develops diabetic nephropathy and requires renal transplant. These groups of patients can undergo simultaneous kidney-pancreas (SKP) transplant. Pancreas transplant alone (PTA) is performed in patients with type 1 diabetes who have labile diabetes and hypoglycemic unawareness. More than 80% of pancreas transplants in the US are SKP transplants and about 11% are isolated pancreas (PTA) and rest are pancreas after kidney.
Most of the pancreatic graft comes from DBD donors, although few living-donor pancreas transplantations have been performed.
| Transplantation in India|| |
The number of solid-organ transplants being done in India has steadily increased. However, there are two big hindrances to growth of transplants in India. The rate of organ DBD has remained low. The deceased donation rate in India is approximately 0.34/million of population which is much below when compared to organ donation rate prevalent in other countries such as Croatia's 36.5, Spain's 35.3, and America's 26/million, respectively. Even with an increase in organ donation rate to 1/million of population India would have 1100 organ donors or 2200 eyes, 2200 kidneys, 1100 livers, 1100 pancreas, and 1000 hearts. This should take care of almost all the current demands for organs.
Other issue which needs to be addressed urgently is availability of organ transplantation as treatment option for every one in India. Majority of transplants in India are being done in private hospitals and majority of cadaveric donations are also happening in private hospitals. Organ transplants in private hospital are costly options for majority of Indians. India needs to develop the government-run tertiary health-care facilities where transplants can be done at a subsidized rate so that anyone requiring organ transplant can get benefited.
| Future of Transplant|| |
The disparity between demand of organ and supply is increasing, and a lot of research is being done to narrow this gap.
- Improvements in organ preservation: Trials are going on using normothermic and hypothermic machine perfusion of grafts before transplant; that may increase the graft preservation time as well as will permit assessment of organ function before transplant
- Organ repair pretransplant: These perfusion technologies also allow the possibility of pretransplant repair of organs who were not suitable for transplant using pharmacological intervention or genetic manipulation 
- Tolerance: Large number of grafts and recipients are lost in the long run due to side effects of immunosuppressive agents. Transplantation tolerance is a state in which the immune system of the recipient of a tissue or organ transplantation does not attack the transplanted tissue. Research to induce tolerance where a recipient will not need immunosuppression is also ongoing 
- Bioartificial organs: The ultimate approach to the shortage of donor organs is likely to be some version of the manufacture and transplantation of bioartificial organs. The recellularization of organ scaffolds using stem cells or more differentiated cell precursors has great potential for the production of transplantable organs. The potential to produce organ scaffolds and populate scaffolds with cells using three-dimensional printing technology is also actively being investigated.
Looking at the future organ transplant, I hope that it should be available for every Indian citizen, and hopefully, no one will die on the waiting list due to the shortage of organs.
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[Figure 1], [Figure 2], [Figure 3]