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Liver transplantation



 
 
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, a few of which are 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 the donor organ is placed 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.

first human
Human

A human being, also human or man, is a member of a species of bipedalism primates in the family Hominidae . Mitochondrial DNA evidence indicates that modern humans originated in east Africa about 200,000 years ago....
 liver transplant was performed in 1963 by a surgical team led by Dr. Thomas Starzl
Thomas Starzl

Thomas E. Starzl is an Health care in the United States, Medical research, 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."...
 of Denver, Colorado
Denver, Colorado

Denver is the Capital and the Colorado municipalities of the state of Colorado, in the United States. Denver is a consolidated city-county located in the South Platte River on 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 government constitutional republic comprising U.S. state and a federal district. The country is situated mostly in central North America, where its Contiguous United States and Washington, D.C., the Capital districts and territories, lie between the Pacific Ocean and Atlantic Oceans, Borders of the U...
.






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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, a few of which are 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 the donor organ is placed 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.

History

The first human
Human

A human being, also human or man, is a member of a species of bipedalism primates in the family Hominidae . Mitochondrial DNA evidence indicates that modern humans originated in east Africa about 200,000 years ago....
 liver transplant was performed in 1963 by a surgical team led by Dr. Thomas Starzl
Thomas Starzl

Thomas E. Starzl is an Health care in the United States, Medical research, 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."...
 of Denver, Colorado
Denver, Colorado

Denver is the Capital and the Colorado municipalities of the state of Colorado, in the United States. Denver is a consolidated city-county located in the South Platte River on 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 government constitutional republic comprising U.S. state and a federal district. The country is situated mostly in central North America, where its Contiguous United States and Washington, D.C., the Capital districts and territories, lie between the Pacific Ocean and Atlantic Oceans, Borders of the U...
. 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 posttransplantation. 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 cyclosporine
Ciclosporin

Ciclosporin , cyclosporine or cyclosporin , is an immunosuppressant medication widely used in Allograft organ transplant to reduce the activity of the patient's immune system and so the risk of organ Transplant rejection....
 by Sir Roy Calne
Roy Calne

Sir Roy Yorke Calne, Royal Society is a United Kingdom surgeon and pioneer in organ transplantation; he performed the first liver transplantation operation in Europe in 1968....
 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 centres 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, a few of which are 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. 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.

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).

Immunosuppressive management

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

Transplant rejection occurs when a Organ transplant organ or tissue is not accepted by the body of the transplant recipient. This is explained by the concept that the immune system of the recipient attacks the transplanted organ or tissue....
 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 conditions....
 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 physiology systems such as stress , immune system and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior....
s plus a calcinuerin inhibitor such as tacrolimus
Tacrolimus

Tacrolimus is an immunosuppression medication whose main use is after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ Transplant rejection....
 or Cyclosporin plus a antimetabolite such as Mycophenolate Mofetil
Mycophenolic acid

Mycophenolic acid or mycophenolate is an Immunosuppression drug used to prevent Transplant rejection in organ transplantation. It was initially marketed as the prodrug mycophenolate mofetil to improve oral bioavailability....
.

Liver transplantation is unique in that the risk of chronic rejection also decreases over time, although recipients need to take immunosuppresive medication for the rest of their lives. 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 collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
. 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 Commonwealth System of Higher Education research university located in Pittsburgh, Pennsylvania, Pennsylvania, United States....
 which consisted of bone marrow
Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
 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 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 from the new liver occurs in 10% to 15% of all cases. These percentages are contributed 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 nonfunctioning graft.

Living donor transplantation

Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical
Surgery

Surgery is a 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, to help improve bodily function or appearance, or sometimes for some other reason....
 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 fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
 and/or hepatocellular carcinoma
Hepatocellular carcinoma

Hepatocellular carcinoma is a primary cancer of the liver. Most cases of HCC are secondary to either a viral hepatitis infection or cirrhosis ....
 often attributable to one or more of the following: long-term alcohol
Alcoholism

Alcoholism is a term with multiple and sometimes conflicting definitions to describe the detrimental effects of alcohol intake.In common and historic usage, alcoholism refers to any condition that results in the continued consumption of alcoholic beverages despite health problems and negative social consequences....
 abuse, long-term untreated Hepatitis C
Hepatitis C

Hepatitis C is a Blood-borne disease infectious disease that is caused by the hepatitis C virus , affecting the liver. The infection is often asymptomatic, but once established, chronic infection can cause inflammation of the liver ....
 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...
ic livers for patients awaiting transplant
Organ transplant

Organ transplant is the moving of an organ from one body to another , for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site....
. 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. Silvano Raia
Silvano Raia

Dr. Silvano Raia is a Brazilian surgeon who specializes in liver diseases. He is a professor emeritus at the Faculty of Medicine of the University of S?o Paulo ....
 at the Universidade de São Paulo (USP) Medical School in 1986. 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....
) 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, a type of fistula where bile leaks from the bile ducts into outside areas, can occur as a complication following biliary Physical trauma, either iatrogenic or a result of a penetrating injury....
, gastric stasis and infection
Infection

An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host resources to multiply ....
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 improve further as surgeons gain more experience in this procedure.

In a typical adult recipient LDLT, 55% of the liver (the right lobe) is removed from a healthy living donor. The donor's liver will regenerate to 100% function within 4-6 weeks and will reach full volumetric size with recapitulation of the normal structure soon thereafter. It may be possible to remove 70% to 75% 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.

Further reading

  • Nadalin S, Malagò M, et al. Current trends in live liver donation. Transpl. Int. 2007;20:312-30.
  • Vohra V. Liver transplantation in India. Int Anesthesiol Clin. 2006;44:137-49.
  • Strong RW. Living-donor liver transplantation: an overview. J Hepatobiliary Pancreat Surg. 2006;13:370-7.
  • Fan ST. Live donor liver transplantation in adults. Transplantation. 2006;82:723-32.


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