Liver transplantation
Overview
 
Liver transplantation or hepatic transplantation is the replacement of a diseased liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure.
Encyclopedia
Liver transplantation or hepatic transplantation is the replacement of a diseased liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. Typically three surgeons and one anesthesiologist are involved, with up to four supporting nurses. The surgical procedure is very demanding and ranges from 4 to 18 hours depending on outcome. Numerous anastomoses and sutures, and many disconnections and reconnections of abdominal and hepatic tissue, must be made for the transplant to succeed, requiring an eligible recipient and a well-calibrated live or cadaveric donor match. By any standard, hepatic transplantation is a major surgical procedure with an appreciable degree of risk.

History

The first human
Human
Humans are the only living species in the Homo genus...

 liver transplant was performed in 1963 by a surgical team led by Dr. Thomas Starzl
Thomas Starzl
Thomas E. Starzl is an American physician, researcher, and is an expert on organ transplants. He performed the first human liver transplants, and has often been referred to as "the father of modern transplantation."-Life:...

 of Denver, Colorado
Denver, Colorado
The City and County of Denver is the capital and the most populous city of the U.S. state of Colorado. Denver is a consolidated city-county, located in the South Platte River Valley on the western edge of the High Plains just east of the Front Range of the Rocky Mountains...

, United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

. Dr. Starzl performed several additional transplants over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post transplantation. 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
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

 by Sir Roy Calne
Roy Calne
Sir Roy Yorke Calne, FRS, is a British surgeon and pioneer in organ transplantation; he performed the first liver transplantation operation in Europe in 1968. His surgical procedures also laid claim to many other pioneering successes in his career: the world's first liver, heart, and lung...

 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. Liver transplantation is now performed at over one hundred centers in the USA, as well as numerous centres in Europe and elsewhere. One year patient survival is 80-85%, and outcomes continue to improve, although liver transplantation remains a formidable procedure with frequent complications. Unfortunately, the supply of liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 allografts from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of living donor liver transplantation.

Indications

Liver transplantation is potentially applicable to any acute or chronic condition resulting in irreversible liver dysfunction, provided that the recipient does not have other conditions that will preclude a successful transplant. Uncontrolled metastatic cancer outside liver, active drug or alcohol abuse and active septic infections are absolute contraindications. While infection with HIV was once considered an absolute contraindication, this has been changing recently. Advanced age and serious heart, pulmonary or other disease may also prevent transplantation (relative contraindications). Most liver transplants are performed for chronic liver diseases that lead to irreversible scarring of the liver, or cirrhosis of the liver. Another cause is cryptogenic liver disease. Some centers use the Milan criteria
Milan criteria
In transplantation medicine, the Milan criteria are applied as a basis for selecting patients with cirrhosis and hepatocellular carcinoma for liver transplantation.The Milan criteria state that a patient is selected for transplantation when he or she has:...

 to select patients for liver transplantation.

Techniques

Before transplantation, liver-support therapy might be indicated (bridging-to-transplantation). Artificial liver support like liver dialysis
Liver dialysis
Liver dialysis is a detoxification treatment for liver failure and has shown promise for patients with hepatorenal syndrome. It is similar to hemodialysis and based on the same principles...

 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
Viaspan
Viaspan, also known as University of Wisconsin solution , was the first solution thoughtfully designed for use in organ transplantation, and became the first intracellular-like preservation medium...

) or HTK
Histidine-tryptophan-ketoglutarate
Histidine-tryptophan-ketoglutarate, or Custodiol HTK solution is a high-flow, low-potassium preservation solution used for organ transplantation....

 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.

Immunosuppressive management

Like most other allografts, a liver transplant will be rejected
Transplant rejection
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...

 by the recipient unless immunosuppressive
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...

 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 corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

s plus a calcineurin inhibitor such as tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...

 or ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

 plus a purine antagonist such as mycophenolate mofetil
Mycophenolic acid
Mycophenolic acid INN or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It inhibits an enzyme needed for the growth of T cells and B cells. It was initially marketed as the prodrug mycophenolate mofetil to improve oral bioavailability. More...

. Clinical outcome is better with tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...

 than with ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

 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 recipients need to take immunosuppressive medication for the rest of their lives. It is possible to be slowly taken off an 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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

. There is at least one study by Dr. Starzl's team at the University of Pittsburgh
University of Pittsburgh
The University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...

 which consisted of bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 biopsies taken from such patients which demonstrate genotypic chimerism in the bone marrow of liver transplant recipients.

Graft rejection

After a liver transplantation, there are three types of graft rejection that may occur. They include hyperacute rejection, acute rejection and chronic rejection. Hyperacute rejection is caused by preformed anti-donor antibodies. It is characterized by the binding of these antibodies to antigens on vascular endothelial cells. Complement activation
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

 is involved and the effect is usually profound. Hyperacute rejection happens within minutes to hours after the transplant procedure. Unlike hyperacute rejection, which is B cell mediated, acute rejection is mediated by T cells. It involves direct cytotoxicity and cytokine mediated pathways. Acute rejection is the most common and the primary target of immunosuppressive agents. Acute rejection is usually seen within days or weeks of the transplant. Chronic rejection is the presence of any sign and symptom of rejection after 1 year. The cause of chronic rejection is still unknown but an acute rejection is a strong predictor of chronic rejections.
Liver rejection may happen anytime after the transplant. Lab findings of a liver rejection include abnormal AST, ALT, GGT and liver function values such as prothrombin time, ammonia level, bilirubin level, albumin concentration, and blood glucose. Physical findings include encephalopathy, jaundice, bruising and bleeding tendency. Other nonspecific presentation are malaise, anorexia, muscle ache, low fever, slight increase in white blood count and graft tender.

Results

Prognosis is quite good. However, those with certain illnesses may differ. There is no exact model to predict survival rates; however, 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.

Living donor transplantation

Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

 option for patients with end stage liver disease, such as cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

 and/or hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...

 often attributable to one or more of the following: long-term alcohol abuse
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

, long-term untreated hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

 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 cadaver
Cadaver
A cadaver is a dead human body.Cadaver may also refer to:* Cadaver tomb, tomb featuring an effigy in the form of a decomposing body* Cadaver , a video game* cadaver A command-line WebDAV client for Unix....

ic livers for patients awaiting transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...

. 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 as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace their child's entire damaged liver. The first report of successful LDLT was by Dr. Christoph Broelsch
Christoph Broelsch
Christoph Broelsch is a German surgeon and former high school teacher. Broelsch pioneered the liver transplant surgery. In 1989 he was the first to successfully perform a live liver transplant.- Life and Work :...

 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 (hepatectomy
Hepatectomy
Hepatectomy consists on the surgical resection of the liver. While the term is often employed for the removal of the liver from a liver transplant recipient, this article will focus on partial resections of hepatic tissue.-History:...

) 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
Biliary fistula
A biliary fistula is a type of fistula where bile leaks from the bile ducts into outside areas.-Causes:It can occur as a complication following biliary trauma , either iatrogenic or a result of a penetrating injury.-Presentation:...

, gastric stasis and infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s; 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.

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. http://www.reachmd.com/xmsegment.aspx?sid=1675

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.

Liver donor requirements

Any member of the family, parent, sibling, child, spouse or a volunteer can donate their liver. The criteria for a liver donation include:
  • Being in good health
  • Having a blood type
    Blood type
    A blood type is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells . These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system...

     that matches or is compatible with the recipient's
  • Having a charitable desire of donation without financial motivation
  • Being between 18 and 60 years old
  • Being of similar or bigger size than the recipient
  • Before one becomes a living donor, the donor must undergo testing to ensure that the individual is physically fit. Sometimes CT scans or MRIs are done to image the liver. In most cases, the work up is done in 2–3 weeks Who can be a Donor? - University of Maryland Medical Center, Retrieved on 2010-01-20.

Complications

Living donor surgery is done at a major center. Very few individuals require any blood transfusions during or after surgery. Even though the procedure is very safe, 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.

Pediatric transplantation

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.

Benefits

There are several advantages of living liver donor transplantation over cadaveric donor transplantation, including:
  • Transplant can be done on an elective basis because the donor is readily available
  • There are fewer possibilities for complications and death while waiting for a cadaveric organ donor
  • Because of donor shortages, UNOS has limited the cadaveric organ allocation to foreigners who seek medical help in the USA. However, with the availability of living donor transplantation, this will now allow foreigners a new opportunity to seek medical care in the USA

Screening for donors

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, confidentially 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
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...

, surgeons today are able to perform transplantation without problems. The most important criterion for a living liver donor is to be in excellent health.

Economic aspect

Typical expenses during the first year (everything included from surgey, hospitalization, lab testing, medications) are up to $315,000, excluding insurance or government assistance.
The cost is considerably lower in countries like India where a living donor liver transplant typically costs about $150,000/-. The high volume of such procedures in a few centers in India results in excellent outcomes comparable to the best centers in the world http://www.livertransplants.co.in/cost.

Controversy over eligibility for alcoholics


The high incidence of liver transplants given to those with alcoholic cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

 has led to a recurring controversy regarding the eligibility of such patients for liver transplant. The controversy stems from the view of alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

as a self-inflicted disease and the perception that those with alcohol-induced damage are depriving other patients who could be considered more deserving.

External links


The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK