Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. The surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. Liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. The duration of the surgery ranges from 4 to 18 hours depending on outcome.[ medical citation needed ] Favorable outcomes require careful screening for eligible recipient, as well as a well-calibrated live or cadaveric donor match.[ medical citation needed ]
Liver transplantation is a potential treatment for acute or chronic conditions which cause irreversible and severe ("end-stage") liver dysfunction.Since the procedure carries relatively high risks, is resource-intensive, and requires major life-modifications after surgery, it is reserved for dire circumstances.
Judging the appropriateness/effectiveness of liver transplant on case-by-case basis is critically important (see Contraindications ), as outcomes are highly variable.
Although liver transplantation is the most effective treatment for many forms of end-stage liver disease, the tremendous limitation in allograft availability and widely variable post-surgical outcomes make case selection critically important. Assessment of a person's transplant eligibility is made by a multi-disciplinary team that includes surgeons, medical doctors, and other providers.
The first step in evaluation is to determine whether the patient has irreversible liver-based disease which will be cured by getting a new liver.Thus, those with diseases which are primarily based outside the liver or have spread beyond the liver are generally considered poor candidates. Some examples include:
Importantly, many contraindications to liver transplantation are considered reversible; a person initially deemed "transplant-ineligible" may later become a favorable candidate if their situation changes.Some examples include:
After a liver transplantation, immune-mediated rejection (also known as rejection) of the allograft may happen at any time. Rejection may present with lab findings: elevated AST, ALT, GGT; abnormal liver function values such as prothrombin time, ammonia level, bilirubin level, albumin concentration; and abnormal blood glucose. Physical findings may include encephalopathy, jaundice, bruising and bleeding tendency. Other nonspecific presentation may include malaise, anorexia, muscle ache, low fever, slight increase in white blood count and graft-site tenderness.
Three types of graft rejection may occur: hyperacute rejection, acute rejection, and chronic rejection.
Before transplantation, liver-support therapy might be indicated (bridging-to-transplantation). Artificial liver support like liver dialysis or bioartificial liver support concepts are currently under preclinical and clinical evaluation. Virtually all liver transplants are done in an orthotopic fashion; that is, the native liver is removed and the new liver is placed in the same anatomic location.The transplant operation can be conceptualized as consisting of the hepatectomy (liver removal) phase, the anhepatic (no liver) phase, and the postimplantation phase. The operation is done through a large incision in the upper abdomen. The hepatectomy involves division of all ligamentous attachments to the liver, as well as the common bile duct, hepatic artery, hepatic vein and portal vein. Usually, the retrohepatic portion of the inferior vena cava is removed along with the liver, although an alternative technique preserves the recipient's vena cava ("piggyback" technique).
The donor's blood in the liver will be replaced by an ice-cold organ storage solution, such as UW (Viaspan) or HTK until the allograft liver is implanted. Implantation involves anastomoses (connections) of the inferior vena cava, portal vein, and hepatic artery. After blood flow is restored to the new liver, the biliary (bile duct) anastomosis is constructed, either to the recipient's own bile duct or to the small intestine. The surgery usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the surgeon.
The large majority of liver transplants use the entire liver from a non-living donor for the transplant, particularly for adult recipients. A major advance in pediatric liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult liver is used for an infant or small child. Further developments in this area included split liver transplantation, in which one liver is used for transplants for two recipients, and living donor liver transplantation, in which a portion of a healthy person's liver is removed and used as the allograft. Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3).
Further advance in liver transplant involves only resection of the lobe of the liver involved in tumors and the tumor-free lobe remains within the recipient. This speeds up the recovery and the patient stay in the hospital quickly shortens to within 5–7 days.
Many major medical centers are now using radiofrequency ablation of the liver tumor as a bridge while awaiting for liver transplantation. This technique has not been used universally and further investigation is warranted.[ medical citation needed ]
Between removal from donor and transplantation into the recipient, the allograft liver is stored in a temperature-cooled preservation solution. The reduced temperature slows down the process of deterioration from normal metabolic processes, and the storage solution itself is designed to counteract the unwanted effects of cold ischemia. Although this "static" cold storage method has long been standard technique, various dynamic preservation methods are under investigation. For example, systems which use a machine to pump blood through the explanted liver (after it is harvested from the body) during a transfer have met some success (see Research section for more).
Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma often attributable to one or more of the following: long-term alcohol abuse, long-term untreated hepatitis C infection, long-term untreated hepatitis B infection. The concept of LDLT is based on (1) the remarkable regenerative capacities of the human liver and (2) the widespread shortage of cadaveric livers for patients awaiting transplant. In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the recipient’s diseased liver has been entirely removed.
Historically, LDLT began with terminal pediatric patients, whose parents were motivated to risk donating a portion of their compatible healthy livers to replace their children's failing ones. The first report of successful LDLT was by Christoph Broelsch at the University of Chicago Medical Center in November 1989, when two-year-old Alyssa Smith received a portion of her mother's liver.Surgeons eventually realized that adult-to-adult LDLT was also possible, and now the practice is common in a few reputable medical institutes. It is considered more technically demanding than even standard, cadaveric donor liver transplantation, and also poses the ethical problems underlying the indication of a major surgical operation (hemihepatectomy or related procedure) on a healthy human being. In various case series, the risk of complications in the donor is around 10%, and very occasionally a second operation is needed. Common problems are biliary fistula, gastric stasis and infections; they are more common after removal of the right lobe of the liver. Death after LDLT has been reported at 0% (Japan), 0.3% (USA) and <1% (Europe), with risks likely to decrease further as surgeons gain more experience in this procedure. Since the law was changed to permit altruistic non-directed living organ donations in the UK in 2006, the first altruistic living liver donation took place in Britain in December 2012.
In a typical adult recipient LDLT, 55 to 70% of the liver (the right lobe) is removed from a healthy living donor. The donor's liver will regenerate approaching 100% function within 4–6 weeks, and will almost reach full volumetric size with recapitulation of the normal structure soon thereafter. It may be possible to remove up to 70% of the liver from a healthy living donor without harm in most cases. The transplanted portion will reach full function and the appropriate size in the recipient as well, although it will take longer than for the donor.
Living donors are faced with risks and/or complications after the surgery. Blood clots and biliary problems have the possibility of arising in the donor post-op, but these issues are remedied fairly easily. Although death is a risk that a living donor must be willing to accept prior to the surgery, the mortality rate of living donors in the United States is low. The LDLT donor's immune system does diminish as a result of the liver regenerating, so certain foods which would normally cause an upset stomach could cause serious illness.[ citation needed ]
Any member of the family, parent, sibling, child, spouse or a volunteer can donate their liver. The criteriafor a liver donation include:
Living donor surgery is done at a major center. Very few individuals require any blood transfusions during or after surgery. All potential donors should know there is a 0.5 to 1.0 percent chance of death. Other risks of donating a liver include bleeding, infection, painful incision, possibility of blood clots and a prolonged recovery.The vast majority of donors enjoy complete and full recovery within 2–3 months.
In children, living liver donor transplantations have become very accepted. The accessibility of adult parents who want to donate a piece of the liver for their children/infants has reduced the number of children who would have otherwise died waiting for a transplant. Having a parent as a donor also has made it a lot easier for children - because both patients are in the same hospital and can help boost each other's morale.
There are several advantages of living liver donor transplantation over cadaveric donor transplantation, including:
Living donor transplantation is a multidisciplinary approach. All living liver donors undergo medical evaluation. Every hospital which performs transplants has dedicated nurses that provide specific information about the procedure and answer questions that families may have. During the evaluation process, confidentiality is assured on the potential donor. Every effort is made to ensure that organ donation is not made by coercion from other family members. The transplant team provides both the donor and family thorough counseling and support which continues until full recovery is made.
All donors are assessed medically to ensure that they can undergo the surgery. Blood type of the donor and recipient must be compatible but not always identical. Other things assessed prior to surgery include the anatomy of the donor liver. However, even with mild variations in blood vessels and bile duct, surgeons today are able to perform transplantation without problems. The most important criterion for a living liver donor is to be in excellent health.
Like most other allografts, a liver transplant will be rejected by the recipient unless immunosuppressive drugs are used. The immunosuppressive regimens for all solid organ transplants are fairly similar, and a variety of agents are now available. Most liver transplant recipients receive corticosteroids plus a calcineurin inhibitor such as tacrolimus or ciclosporin, (also spelled cyclosporine and cyclosporin) plus a purine antagonist such as mycophenolate mofetil. Clinical outcome is better with tacrolimus than with ciclosporin during the first year of liver transplantation.If the patient has a co-morbidity such as active hepatitis B, high doses of hepatitis B immunoglubins are administrated in liver transplant patients.
Liver transplantation is unique in that the risk of chronic rejection also decreases over time, although the great majority of recipients need to take immunosuppressive medication for the rest of their lives. It is possible to be slowly taken off anti rejection medication but only in certain cases. It is theorized that the liver may play a yet-unknown role in the maturation of certain cells pertaining to the immune system [ citation needed ]. There is at least one study by Thomas E. Starzl's team at the University of Pittsburgh which consisted of bone marrow biopsies taken from such patients which demonstrate genotypic chimerism in the bone marrow of liver transplant recipients.
The prognosis following liver transplant is variable, depending on overall health, technical success of the surgery, and the underlying disease process affecting the liver.There is no exact model to predict survival rates; those with transplant have a 58% chance of surviving 15 years. Failure of the new liver occurs in 10% to 15% of all cases. These percentages are contributed to by many complications. Early graft failure is probably due to preexisting disease of the donated organ. Others include technical flaws during surgery such as revascularization that may lead to a nonfunctioning graft.
As with many experimental models used in early surgical research, the first attempts at liver transplantation were performed on dogs. The earliest published reports of canine liver transplantations were performed in 1955 by Vittorio Staudacher at Opedale Maggiore Policlinico in Milan, Italy. This initial attempt varied significantly from contemporary techniques; for example, Staudacher reported "arterialization" of the donor portal vein via the recipient hepatic artery, and use of cholecystostomy for biliary drainage.
The first attempted human liver transplant was performed in 1963 by Thomas Starzl, although the pediatric patient died intraoperatively due to uncontrolled bleeding. [ medical citation needed ] Liver transplantation is now performed at over one hundred centers in the US, as well as numerous centres in Europe and elsewhere.Multiple subsequent attempts by various surgeons remained unsuccessful until 1967, when Starzl transplanted a 19 month old girl with hepatoblastoma who was able to survive for over 1 year before dying of metastatic disease. Despite the development of viable surgical techniques, liver transplantation remained experimental through the 1970s, with one year patient survival in the vicinity of 25%. The introduction of ciclosporin by Sir Roy Calne, Professor of Surgery Cambridge, markedly improved patient outcomes, and the 1980s saw recognition of liver transplantation as a standard clinical treatment for both adult and pediatric patients with appropriate indications.
The limited supply of liver allografts from non-living donors relative to the number of potential recipients spurred the development of living donor liver transplantation. The first altruistic living liver donation in Britain was performed in December 2012 in St James University Hospital Leeds.
There is increasing interest in improving methods for allograft preservation following organ harvesting. The standard "static cold storage" technique relies on decreased temperature to slow of anaerobic metabolic breakdown. This is currently being investigated at cold (hypothermic), body temperature (normothermic), and under body temperature (subnormothermic). Hypothermic machine perfusion has been used successfully at Columbia University and at the University of Zurich. °C) More recently, the first randomised controlled clinical trial comparing machine preservation with conventional cold storage showed comparable outcomes, with better early function, fewer discarded organs, and longer preservation times compared with cold stored livers.A 2014 study showed that the liver preservation time could be significantly extended using a supercooling technique, which preserves the liver at subzero temperatures (-6
The high incidence of liver transplants given to those with alcoholic cirrhosis has led to a recurring controversy regarding the eligibility of such patients for liver transplant. The controversy stems from the view of alcoholism as a self-inflicted disease and the perception that those with alcohol-induced damage are depriving other patients who could be considered more deserving.It is an important part of the selection process to differentiate transplant candidates who suffer from alcoholism as opposed to those who were susceptible to non-dependent alcohol use. The latter who gain control of alcohol use have a good prognosis following transplantation. Once a diagnosis of alcoholism has been established, however, it is necessary to assess the likelihood of future sobriety.
Historically, HIV was considered an "absolute" contraindication to liver transplantation. This was in part due to concern that the infection would be worsened by the immunosuppressive medication which is required after transplantation.
However, with the advent of highly active antiretroviral therapy (HAART), people with HIV have much improved prognosis. Transplantation may be offered selectively, although consideration of overall health and life circumstances may still be limiting. Uncontrolled HIV disease (AIDS) remains an absolute contraindication.
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transported from a donor site to another location. Organs and/or tissues that are transplanted within the same person's body are called autografts. Transplants that are recently performed between two subjects of the same species are called allografts. Allografts can either be from a living or cadaveric source.
A pancreas transplant is an organ transplant that involves implanting a healthy pancreas into a person who usually has diabetes. Because the pancreas is a vital organ, performing functions necessary in the digestion process, the recipient's native pancreas is left in place, and the donated pancreas is attached in a different location. In the event of rejection of the new pancreas, which would quickly cause life-threatening diabetes, there would be a significant chance the recipient would not survive very well for long without the native pancreas, however dysfunctional, still in place. The healthy pancreas comes from a donor who has just died or it may be a partial pancreas from a living donor. At present, pancreas transplants are usually performed in persons with insulin-dependent diabetes, who can develop severe complications. Patients with the most common, and deadliest, form of pancreatic cancer are usually not eligible for valuable pancreatic transplantations, since the condition usually has a very high mortality rate and the disease, which is usually highly malignant and detected too late to treat, could and probably would soon return. Better surgical method can be chosen to minimize the surgical complications with enteric or bladder drainage. Advancement in immunosuppression has improved quality of life after transplantation.
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.
Everolimus is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an inhibitor of mammalian target of rapamycin (mTOR).
Xenotransplantation, or heterologous transplant is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation, syngeneic transplantation or isotransplantation and autotransplantation.
Allotransplant is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts.
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease, and indicates that the liver has sustained severe damage. The complications are hepatic encephalopathy and impaired protein synthesis. The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.
Kidney transplantation or renal transplantation is the organ transplant of a kidney into a patient with end-stage kidney disease. Kidney transplantation is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ.
Lung transplantation, or pulmonary transplantation, is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor. Donor lungs can be retrieved from a living donor or a deceased donor. A living donor can only donate one lung lobe. With some lung diseases, a recipient may only need to receive a single lung. With other lung diseases such as cystic fibrosis, it is imperative that a recipient receive two lungs. While lung transplants carry certain associated risks, they can also extend life expectancy and enhance the quality of life for end-stage pulmonary patients.
Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person.
Organ procurement is a surgical procedure that removes organs or tissues for reuse, typically for organ transplantation.
The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces biochemicals necessary for digestion and growth. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm. Its other roles in metabolism include the regulation of glycogen storage, decomposition of red blood cells and the production of hormones.
Transplantable organs and tissues may both refer to organs and tissues that are relatively often or routinely transplanted, as well as relatively seldom transplanted organs and tissues and ones on the experimental stage.
Sander S. Florman, M.D., is an American transplant surgeon and Director of the Recanati/Miller Transplantation Institute at The Mount Sinai Hospital in New York City. He is a member of the American Society of Transplant Surgeons, the American Hepato-Pancreato-Biliary Association, the American Society of Transplantation and the American College of Surgeons.
A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease when other medical or surgical treatments have failed. As of 2018, the most common procedure is to take a functioning heart, with or without both lungs, from a recently deceased organ donor and implanting it into the patient. The patient's own heart is either removed and replaced with the donor heart or, much less commonly, the recipient's diseased heart is left in place to support the donor heart.
Thomas D. Schiano, M.D., is an American specialist in liver transplantation, intestinal transplantation and in the diagnosis and treatment of acute and chronic liver disease. He serves as associate editor for the journals Hepatology and Liver Transplantation and has published more than 200 peer-reviewed articles and abstracts and more than 20 book chapters.
ABO-incompatible (ABOi) transplantation is a method of allocation in organ transplantation that permits more efficient use of available organs regardless of ABO blood type, which would otherwise be unavailable due to hyperacute rejection. Primarily in use in infants and young toddlers, research is ongoing to allow for increased use of this capability in adult transplants. Normal ABO-compatibility rules may be observed for all recipients. This means that anyone may receive a transplant of a type-O organ, and consequently, type-O recipients are one of the biggest beneficiaries of ABO-incompatible transplants. While focus has been on infant heart transplants, the principles generally apply to other forms of solid organ transplantation.
Prof (Dr) Subhash Gupta is the Chief liver transplant/hepato-pancreato-biliary surgeon and the Chairman of the Max Center of Liver and Biliary Sciences at Max Hospital, Saket.
Intestine transplantation is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. While intestinal failure can oftentimes be treated with alternative therapies such as parenteral nutrition (PN), complications such as PN-associated liver disease and short bowel syndrome may make transplantation the only viable option. One of the rarest type of organ transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in immunosuppressive regimens, surgical technique, PN, and the clinical management of pre and post-transplant patients.
Ernesto Pompeo Molmenti, MD, PhD, MBA is an American transplant surgeon, scientist, and author. Currently practicing in Long Island, New York. He is Chief of Surgical Innovation and Vice-Chairman of the Department of Surgery at North Shore University Hospital / Northwell Health, and Professor of Surgery, Medicine, and Pediatrics at Zucker School of Medicine at Hofstra/Northwell. He is known by the development of a vascular reconstruction technique that has been named "Molmenti technique".