Liver transplantation is the replacement of a diseased liver 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 liver transplant was done in 1963 by Dr. Thomas Starzl of  Denver, Colorado and by Sir Roy Caine of the University of Cambridge, England. 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 cyclosporine by Sir Roy Calne 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 centers in Europe and elsewhere. One year patient survival is 85-90%, and outcomes continue to improve, although liver transplantation remains a formidable procedure with frequent complications. Unfortunately, the supply of liver 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.

Techniques

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, 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). After the hepatectomy is accomplished, the allograft liver is implanted. This 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 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 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 either tacrolimus or cyclosporin.

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. There is at least one study by Dr. 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.

Results

Prognosis is quite good. 1-year survival (in Finland) is 83%, 5-year survival is 76% and 10-year survival is 66%. Majority of deaths happen during the first three months after transplantation.

Liver Transplant Overview
(the following information from WebMD)

Currently, more than 17,000 people in the United States are waiting for liver transplants. According to the United Network for Organ Sharing (UNOS), about 5,300 liver transplantations were performed in the United States in 2002.

The liver is the second most commonly transplanted major organ, after the kidney, so it is clear that liver disease is a common and serious problem in this country. It is important for liver transplant candidates and their families to understand the basic process involved with liver transplants, to appreciate some of the challenges and complications that face liver transplant recipients (people who receive livers), and to recognize symptoms that should alert recipients to seek medical help.

Some basics are as follows:

• The liver donor is the person who gives, or donates, all or part of his or her liver to the waiting patient who needs it. Donors are usually people who have died and wish to donate their organs. Some people, however, donate part of their liver to another person (often a relative) while living.

• Orthotopic liver transplantation refers to a procedure in which a failed liver is removed from the patient's body and a healthy donor liver is transplanted into the same location. In this case, the liver donor is someone who has recently died. The procedure is the most common method used to transplant livers.

• With a living donor transplant, a healthy person donates part of his or her liver to the recipient. This procedure has been increasingly successful and shows promise as a solution to the shortage of liver donors. It is becoming the most frequent option in children, partly because child-sized livers are in such short supply. Other methods of transplantation are used for people who have potentially reversible liver damage or as temporary measures for those who are awaiting liver transplants. These other methods are not discussed in detail in this article.

• The body needs a healthy liver. The liver is an organ located in the right side of the abdomen below the ribs. The liver has many vital functions.

• It is a powerhouse that produces varied substances in the body, including (1) glucose, a basic sugar and energy source; (2) proteins, the building blocks for growth; (3) blood-clotting factors, substances that aid in healing wounds; and (4) bile, a fluid stored in the gallbladder and necessary for the absorption of fats and vitamins.

• As the largest solid organ in the body, the liver is ideal for storing important substances like vitamins and minerals. It also acts as a filter, removing impurities from the blood. Finally, the liver metabolizes and detoxifies substances ingested by the body. Liver disease occurs when these essential functions are disrupted. Liver transplants are needed when damage to the liver severely impairs a person's health and quality of life.

• Determining whose need is most critical: The United Network for Organ Sharing uses measurements of clinical and laboratory problems to divide patients into groups that determine who is in most critical need of a liver transplant. In early 2002, UNOS enacted a major modification to the way in which people were assigned the need for a liver transplant. Previously, patients awaiting livers were ranked as status 1, 2A, 2B, and 3, according to the severity of their current disease. Although the status 1 listing has remained, all other patients are now classified using the Model for End-Stage Liver Disease (MELD) scoring system if they are aged 18 years or older, or the Pediatric End-Stage Liver Disease (PELD) scoring system if they are younger than 18 years. These scoring methods were set up so that donor livers could be distributed to those who need them most urgently.
   
  • Status 1 (acute severe disease) is defined as a patient with only recent development of liver disease who is in the intensive care unit of the hospital with a life expectancy without a liver transplant of fewer than 7 days.
     
  • MELD scoring: This system is based on the risk or probability of death within 3 months if the patient does not receive a transplant. The MELD score is calculated based only on laboratory data in order to be as objective as possible. The laboratory values used are a patient’s creatinine, bilirubin, and international normalized ratio, or INR (a measure of blood-clotting time). A patient’s score can range from 6 to 40. In the event of a liver becoming available to 2 patients with the same MELD score and blood type, time on the waiting list becomes the deciding factor.
     
  • PELD scoring: This system is based on the risk or probability of death within 3 months if the patient does not receive a transplant. The PELD score is calculated based on laboratory data and growth parameters. The laboratory values used are a patient’s albumin, bilirubin, and INR (measure of blood-clotting capability). These values are used together with the patient’s degree of growth failure to determine a score that can range from 6 to 40. As with the adult system, if a liver were to become available to two similarly sized patients with the same PELD score and blood type, the child who has been on the waiting list the longest will get the liver.
     
  • Based on this system, livers are first offered locally to status 1 patients, then according to patients with the highest MELD or PELD scores. Next, if there are no local recipients, the liver is offered regionally, in the same order, and finally, on a national level.
     
  • Status 7 (inactive) is defined as patients who are considered to be temporarily unsuitable for transplantation.
   
• Who may not be given a liver: A person who needs a liver transplant may not qualify for one because of the following reasons:
   
  • Active alcohol or substance abuse: Persons with active alcohol or substance abuse problems may continue living the unhealthy lifestyle that contributed to their liver damage. Transplantation would only result in failure of the newly transplanted liver.
     
  • Cancers in locations other than just the liver weigh against a transplant.
     
  • Advanced heart and lung disease: These conditions prevent a transplanted liver from surviving.
     
  • Severe infection: Such infections are a threat to a successful procedure.
     
  • Massive liver failure: This type of liver failure accompanied by associated brain injury from increased fluid in brain tissue rules against a liver transplant.
     
  • HIV infection
   
• The transplantation team: If a liver transplant is recommended by a primary doctor, the person must also be evaluated by a transplantation team. The usual candidate has advanced liver disease but is otherwise in good health.
   
  • The transplantation team usually consists of a transplant coordinator, a hepatologist (liver specialist), and a transplant surgeon. It may be necessary to see a cardiologist (heart specialist) and pulmonologist (lung specialist), depending on the recipient's age and health problems.
     
  • The potential recipient may also see a psychiatrist because the liver transplantation process may be a very emotional experience that may require life adjustments.
     
  • The liver specialist and the primary doctor manage the person’s health issues until the time of transplantation.
     
  • A social worker may be involved in the case. This person assesses and helps develop the patient's support system, a central group of people on whom the patient can depend throughout the transplantation process. A positive support group is very important to a successful outcome. The support group can be instrumental in ensuring that the patient takes all the required medicines, which may have unpleasant side effects. The social worker also checks to see that the recipient is taking medications appropriately.

• The search for a donor: Once a person is accepted for transplantation, the search for a suitable donor begins. All people waiting are placed on a central list at UNOS. Local and national agencies are involved in finding suitable livers. The United States has been divided into regions to try to fairly distribute this scarce resource. Many donors are victims of some sort of trauma and have been declared brain dead. A donor with the right blood type and similar body weight is sought to help reduce the risk of rejection. Rejection occurs when the patient's body attacks the new liver.
   
  • With the shortage of donor organs and the need to match donor and patient blood and body type, the waiting time may be long. A patient with a very common blood type has less chance of quickly finding a suitable liver because so many others with his or her blood type also need livers. Such patients are likely to receive a liver only if they are in the intensive care unit and have very severe liver disease. A patient with an uncommon blood type may receive a transplant more quickly if a matching liver is identified because people higher on the transplant list may not have this unusual blood type.
     
  • The length of time a person waits for a new liver depends on blood type, body size, and how soon the patient needs a transplant. During the wait, it is important to stay in good physical health. Following a nutritious diet and a light exercise plan are important. In addition, regularly scheduled visits with the transplantation team may be scheduled for health examinations. A patient also receives vaccines against certain bacteria and viruses that are more likely to develop after the transplantation because of immunosuppression (antirejection) medication.

• Living donors: Avoiding a long wait is possible if a person with liver disease has a living donor who is willing to donate part of his or her liver. This procedure is known as living donor liver transplantation. The donor must have major abdominal surgery to remove the part of the liver that will become the graft (also called a liver allograft, which is the name for the transplanted piece of liver). As techniques in liver surgery have improved, the risk of death in people who donate a part of their liver has dropped to about 1%. The donated liver will be transplanted into the patient. The amount of liver that is donated will be about 50% of the recipient's current liver size. Within 6-8 weeks, both the donated pieces of liver and the remaining part in the donor grow to normal size.
   
  • Until 1999, living donor transplantation was generally considered experimental, but it is now an accepted method. In the future, this procedure will be used more often because of the severe lack of livers from recently deceased donors.
     
  • The live donor procedure also allows greater flexibility for the patient because the procedure may be done for people who are in the lower stages of liver disease.
     
  • At present, only patients with the most severe liver disease are allowed to receive transplants. These are often patients in intensive care units who have a very short life expectancy, often classified as stage 1, or patients with very high MELD or PELD scores.
     
  • With a living donor, patients healthy enough to live at home may still receive a liver transplant. The living donor transplantation may also be more widely used because of the increase in hepatitis C virus infection and the importance of quickly finding transplants for people who have liver cancer. Finally, the success with living donor kidney transplants has encouraged increased use of such techniques.
     
  • Recipients of a living donor liver transplant go through the same evaluation process as those receiving a cadaveric liver (a liver from someone who has died). The donor also has blood tests and imaging studies of the liver performed to make sure it is healthy. The living donors, as with the deceased donors, must have the same blood type as the recipient. They must be aged 18-55 years, have a healthy liver, and be able to tolerate the surgery. The donor cannot receive any money or other form of payment for the donation. Finally, the donor must have a good social support system to aid in emotional aspects of going through the procedure.

    People who have liver disease or alcoholism are not allowed to donate part of their liver. Those who smoke chronically or who are obese or pregnant also cannot make such donations. If the potential donor does not have a compatible blood type or does not meet these criteria, the recipient may continue to be listed on the UNOS registry for a transplant from a deceased donor.

• A donor is found: Once a suitable cadaveric liver donor has been found, the patient is called to the hospital. It is best that the patient carry a beeper as he or she rises on the transplant list, so that getting to the hospital can be done quickly. Donor livers function best if they are transplanted within 8 hours, although they can be used for up to 24 hours. Presurgical studies, including blood tests, urine tests, chest x-rays, and an ECG, are performed. Before surgery, an IV line is started. The patient also receives a dose of steroids—one of the medicines to prevent rejection of the new liver—and a dose of antibiotics to prevent infection. The liver transplantation procedure takes about 6-8 hours. After the transplantation, the patient is admitted to the intensive care unit.