Liver Transplantation

Definition
Purpose
Demographics
Description
Description
Diagnosis/Preparation
Aftercare
Risks
Normal results
Morbidity and mortality
Alternatives

Definition

Liver transplantation is a surgery that removes a diseased liver and replaces it with a healthy donor liver.

Purpose

A liver transplant is needed when the liver’s function is reduced to the point that the life of the patient is threatened.

Demographics

Compared to whites, those with African-American, Asian, Pacific Islander, or Hispanic descent are three times more likely to suffer from end-stage renal disease (ESRD). Both children and adults can suffer from liver failure and require a transplant.

Patients with advanced heart and lung disease, who are human immunodeficiency virus (HIV) positive, and who abuse drugs and alcohol are poor candidates for liver transplantation. Their ability to survive the surgery and the difficult recovery period, as well as their long-term prognosis, is hindered by their conditions.

Description

The liver is the body’s principle chemical factory. It receives all nutrients, drugs, and toxins, which are absorbed from the intestines, and performs the final stages of digestion, converting food into energy and replacement parts for the body. The liver also filters the blood of all waste products, removes and detoxifies poisons, and excretes many of these into the bile. It further processes other chemicals for excretion by the kidneys. The liver is also an energy storage organ, converting food energy to a chemical called glycogen that can be rapidly converted to fuel.

When other medical treatment interferes with the functioning of a damaged liver, a transplant is necessary. Since 1963, when the first human liver transplant was performed, thousands more have been performed each year. Cirrhosis, a disease that kills healthy liver cells, replacing them with scar tissue, is the most common reason for liver transplantation in adults. The most frequent reason for transplantation in children is biliary atresia—a disease in which the ducts that carry bile out of the liver, are missing or damaged.

Included among the many causes of liver failure that bring patients to transplant surgery are:

KEY TERMS

Acetaminophen— A common pain reliever (e.g., Tylenol).

Anesthesia— A safe and effective means of alleviating pain during a medical procedure.

Antibody— An antibody is a protein complex used by the immune system to identify and neutralize foreign objects, such as like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target

Antigen— Any chemical that provokes an immune response.

Ascites— A buildup of fluid in the stomach as a result of liver failure.

Bile ducts— Tubes carrying bile from the liver to the intestines.

Biliary atresia— A disease in which the ducts that carry bile out of the liver are missing or damaged is the most frequent reason for transplantation in children. Biliary atresia of the major bile ducts causes cholestasis and jaundice, which does not become apparent until several days after birth; periportal fibrosis develops and leads to cirrhosis, with proliferation of small bile ducts unless these are also atretic; giant cell transformation of hepatic cells also occurs.

Biliary system— The tree of tubes that carries bile.

Cirrhosis— A disease in which healthy liver cells are killed and replaced with scar tissue. Cirrhosis is the most common reason for liver transplantation in adults and is often a result of alcoholism.

Computed tomography (CT or CAT) scan— A radio-logic imaging modality that uses computer processing to generate an image of the tissue density in a “slice” as thin as 1–10 mm in thickness through the patient’s body. These images are spaced at intervals of 0.5 cm-1 cm. Cross-sectional anatomy can be reconstructed in several planes without exposing the patient to additional radiation. Called also computerized axial tomography (CAT) and computerized transaxial tomography (CTAT).

Electrocardiogram (EKG)— A graphic record showing the electrical activity of the heart.

Endoscopy— An instrument (endoscope) used to visualize a hollow organ’s interior.

Hepatic artery— The blood vessel supplying arterial blood to the liver.

Heterotrophic transplantation— The addition of a donor liver at another site, while the diseased liver is left intact.

Interleukin-2 (IL-2)— A cytokine derived from T helper lymphocytes that causes proliferation of T-lymphocytes and activated B lymphocytes.

Immunosuppression— A disorder or condition where the immune response is reduced or absent.

Inferior vena cava— The biggest vein in the body, returning blood to the heart from the lower half of the body.

Jaundice— Yellowing of the skin and eyes caused by a buildup of bile or excessive breakdown of red blood cells.

Leukemia— A cancer of the white blood cells (WBCs).

Lymphoma— A cancer of lymphatic tissue.

Lymphoproliferative— An increase in the number of lymphocytes. Lymphocytes are a white blood cell (WBC) formed in lymphatic tissue throughout the body—in the lymph nodes, spleen, thymus, tonsils, Peyer patches, and sometimes in bone marrow), and in normal adults, comprising approximately 22-28% of the total number of leukocytes in the circulating blood.

Magnetic resonance imaging (MRI)— A test that provides pictures of organs and structures inside the body by using a magnetic field and pulses of radio wave energy to detect tumors, infection, and other types of tissue disease or damage, and helps to diagnose conditions that affect blood flow. The area of the body being studied is positioned inside a strong magnetic field.

Nephrotoxicity— The quality or state of being toxic to kidney cells.

Orthotopic transplantation— The replacement of a whole diseased liver with a healthy donor liver.

Portal vein— The blood vessel carrying venous blood from the abdominal organs to the liver.

Receptor— A structural protein molecule on the cell surface or within the cytoplasm that binds to a specific factor, such as a drug, hormone, antigen, or neurotransmitter.

• Progressive hepatitis, mostly due to virus infection, accounts for more than one-third of all liver transplants.
• Alcohol damage accounts for approximately 20% of transplants.
• Scarring, or abnormality of the biliary system, accounts for roughly another 20% of liver transplants.
• The remainder of transplants come from various cancers, uncommon diseases, and a disease known as fulminant liver failure.

Fulminant liver failure most commonly happens during acute viral hepatitis, but is also the result of mushroom poisoning by Amanita phalloides and toxic reactions to overdose of some medicines, such as acetaminophen—a medicine commonly used to relieve pain and reduce fever. The person who is the victim of mushroom poisoning is a special category of candidate for a liver transplant because of the speed of the disease and the immediate need for treatment.

As the liver fails, all of its functions diminish. Nutrition suffers, toxins build, and waste products accumulate. Scar tissue accumulates on the liver as the disease progresses. Blood flow is increasingly restricted in the portal vein, which carries blood from the stomach and abdominal organs to the liver. The resulting high blood pressure (hypertension) causes swelling of and bleeding from the blood vessels of the esophagus. Toxins build in the blood (liver encephalopathy), resulting in severe jaundice (yellowing of the skin and eyes), fluid accumulation in the abdomen (ascites), and deterioration of mental function. Eventually, death occurs.

There are three types of liver transplantation methods. They include:

• Orthotopic transplantation, the replacement of a whole diseased liver with a healthy donor liver.
• Heterotrophic transplantation, the addition of a donor liver at another site, while the diseased liver is left intact.
• Reduced-size liver transplantation, the replacement of a whole diseased liver with a portion of a healthy donor liver. Reduced-size liver transplants are most often performed on children.

When an orthotropic transplantation is performed, a segment of the inferior vena cava (the body’s main vein to the heart) attached to the liver is taken from the donor, as well. The same parts are removed from the recipient and replaced by connecting the inferior vena

cava, the hepatic artery, the portal vein, and the bile ducts.

When there is a possibility that the afflicted liver may recover, a heterotypic transplantation is performed. The donor liver is placed in a different site, but it still has to have the same connections. It is usually attached very close to the patient’s original liver; if the original liver recovers, the donor liver will wither away. If the patient’s original liver does not recover, that liver will dry up, leaving the donor in place.

Reduced-size liver transplantation puts part of a donor liver into a patient. A liver can actually be divided into eight pieces—each supplied by a different set of blood vessels. In the past, just two of these sections have been enough to save a patient suffering from liver failure, especially if it is a child. It is possible, therefore, to transplant one liver into at least two patients and to transplant part of a liver from a living donor—and for both the donor and recipients to survive. Liver tissue grows to accommodate its job provided that the organ is large enough initially. Patients have survived with only 15–20% of their original liver intact, assuming that that portion was healthy from the beginning.

As of 2003, the availability of organs for transplant was in crisis. In October 1997, a national distribution system was established that gives priority to patients who are most ill and in closest proximity to the donor livers. Livers, however, are available nationally. It is now possible to preserve a liver out of the body for 10–20 hours by flushing it with cooled solutions of special chemicals and nutrients, if necessary. This enables transport cross-country.

Description

Once a donor liver has been located and the patient is in the operating room and under general anesthesia, the patient’s heart and blood pressure are monitored. A long cut is made alongside of the ribs; sometimes, an upwards cut may also be made. When the liver is removed, four blood vessels that connect the liver to the rest of the body are cut and clamped shut. After getting the donor liver ready, the transplant surgeon connects these vessels to the donor vessels. A connection is made from the bile duct (a tube that drains the bile from the liver) of the donor liver to the bile duct of the liver of the patient’s bile duct. In some cases, a small piece of the intestine is connected to the new donor bile duct. This connection is called Roux-en-Y. The operation usually takes between six and eight hours; another two hours is spent preparing the patient for surgery. Therefore, a patient will likely be in the operating room for eight to 10 hours.

Split-liver techniques means that a single, perfect donor liver from a larger cadaver may be split for transplantation into more than one patient. Usually, the left lobe (comprising about 40% of the entire liver) will go to a small adult, adolescent, or child, while the larger right lobe (comprising about 60% of the entire liver) will go to an adult. When an infant requires a liver transplant, 20% of a normal-sized liver may be utilized, and the other 80% can go to another individual awaiting transplant. The success rate of this split-liver technique is somewhat lower than with whole organs (about 80% success rate versus about 90% success rate), but the obvious advantage is that more patients awaiting transplant can be served.

The United Network for Organ Sharing (UNOS) data indicates that patients in need of organ transplants outnumber available organs three to one.

Diagnosis/Preparation

The liver starts to fail only when more than half of it is damaged. Thus, once a person demonstrates symptoms of liver failure, there is not much liver function left. Signs and symptoms of liver failure include:

• jaundice
• muscle wasting (loss of muscle)
• forgetfulness, confusion, or coma
• fatigue
• itching
• poor blood clotting
• build-up of fluid in the stomach (ascites)
• infections
• bleeding in the stomach

A doctor will diagnose liver disease; a liver specialist, a transplant surgeon, and other doctors will have to be consulted, as well, before a patient can be considered for a liver transplant. Before transplantation takes place, the patient is first determined to be a good candidate for transplantation by going through a rigorous medical examination. Blood tests, consultations, and x rays will be needed to determine if the patient is a good candidate. Other tests that may be conducted are: computed tomography (CAT or CT) scan, magnetic resonance image (MRI), ultrasound, routine chest x ray, endoscopy, sclerotherapy and rubber-band ligation, transjugular intrahepatic portosystemic shunt (TIPS), creatinine clearance, cardiac testing (echocardiogram [ECHO]) and/or electrocardiogram [EKG or ECG]), and pulmonary function test [PFTs]), liver biopsy, and nutritional evaluation. A dietitian will evaluate the patient’s nutritional needs and design an eating plan. Since a patient’s emotional state is as important as their physical state, a psychosocial evaluation will be administered.

Once test results are reviewed and given to the liver transplant selection committee, the patient will be assessed for whether he or she is an appropriate candidate. Some patients are deemed too healthy for a transplant and will be followed and retested at a later date if their liver gets worse. Other patients are determined to be too sick to survive a transplant. The committee will not approve a transplant for these patients. Once a patient is approved, they will be placed on a waiting list for a donor liver. When placed on the waiting list, a patient will be given a score based on the results of the blood tests. The higher a patient’s score, the sicker the patient is. This results in the patient earning a higher place on the waiting list.

Suitable candidates boost their nutritional intakes to ensure that they are as healthy as possible before surgery. Drugs are administered that will decrease organ rejection after surgery. The medical committee consults with the patient and family, if available, to explain the surgery and any potential complications. Many problems can arise during the waiting period. Medicines should be changed as needed, and blood tests should be done to ensure a patient is in the best possible health for the transplant surgery. Psychological counseling during this period is recommended, as well.

When a donor is found, it is important that the transplant team be able to contact the patient. The patient awaiting the organ must not eat or drink anything from the moment the hospital calls. On the other hand, the liver may not be good enough for transplantation. Then, the operation will be cancelled, although this does not happen often.

Aftercare

Following surgery, the patient will wake up in the surgical intensive care unit (SICU). During this time, a tube will be inserted into the windpipe to facilitate breathing. It is removed when the patient is fully awake and strong enough to breathe on his or her own. There may be other tubes that are removed as the patient recovers. When safe to leave the SICU, the patient is moved to the transplant floor. Walking and eating will become the primary focus. Physical therapy may be started to help the patient become active, as it is an important part of recovery. When the patient begins to feel hungry and the bowels are working, regular food that is low in salt will be given.

A patient should expect to spend about 10-14 days in the hospital, although some stays may be shorter or longer. Before leaving the hospital, a patient will be advised of: signs of infection or rejection, how to take medications and change dressings, and how to understand general health problems. Infection can be a real danger, because the medications taken compromise the body’s defense systems. The doctors will conduct blood tests, ultrasounds, and x rays to ensure that the patient is doing well.

The first three months after transplant are the most risky for getting infections, such as the flu, so patients should follow these precautions:

• Avoid from people who are ill.
• Wash hands frequently.
• Tell the doctor if you are exposed to any disease.
• Tell the doctor if a cold sore, rash, or water blister appears on the body or spots appear in the throat or on the tongue.
• Stay out of crowds and rooms with poor circulation.
• Do not swim in lakes or community pools during the three months following transplant.
• Eat meats that are well-cooked.
• Stay away from soil, including those in which houseplants are grown, and gardens, during the three months following transplant.
• Take all medications as directed.
• Learn to report the early symptoms of infection.

To ensure that the transplant is successful and that the patient has a long and healthy life, a patient must get good medical care, prevent and treat complications, keep in touch with doctors and nurses, and follow their advice. Nutrition plays a big part in the success of a liver transplant, so what a patient eats after the transplant is very important.

Medications needed following liver transplantation

Successfully receiving a transplanted liver is only the beginning of a lifelong process. Patients with transplanted livers have to stay on immunosuppressant drugs for the rest of their lives to prevent organ rejection. Although many patients can reduce the dosage after the initial few months, virtually none can discontinue drugs altogether. For adolescent transplant recipients, post transplantation is a particularly difficult time, as they must learn to take responsibility for their own behavior and medication, as well as balance their developing sexuality in a body that has been transformed by the adverse effects of immunosuppression. Long-term outcome and tailoring of immunosuppression is of great importance.

Cyclosporine has long been the drug of experimentation in the immunosuppression regimen, and has been well-tolerated and effective. Hypertension, nephrotoxicity, and posttransplant lymphoproliferative disease (PTLD) are some of the long-term adverse effects. Tacrolimus has been developed more recently, and has improved the cosmetic adverse effects of cyclosporine, but has similar rates of hypertension and nephrotoxicity, and possibly a higher rate of PTLD. Prednisone, azathioprine, and tacrolimus are often combined with cyclosporine for better results. Newer immunosuppressive agents promise even better results.

There has been a recent, welcome development in renal sparing drugs, such as mycophenolate mofetil, which has no cosmetic adverse effects, does not require drug level monitoring, and is thus particularly attractive to teenagers. If started prior to irreversible renal dysfunction, recent research demonstrates recovery of renal function with mycophenolate mofetil. There is little published data on the use of sirolimus (rapamycin) in the pediatric population, but preliminary studies suggest that the future use of interleukin-2 receptor antibodies may be beneficial for immediate post-transplant induction of immunosuppression. When planning immunosuppression for adolescents, it is important to consider the effects of drug therapy on both males and females in order to maintain fertility and to ensure safety in pregnancy. Adequate practical measures and support should reduce noncompliance in this age group, and allow good, long-term function of the transplanted liver.

Risks

Early failure of the transplant occurs once in four surgeries and has to be repeated. Some transplants never work, some patients succumb to infection, and some suffer immune rejection. Primary failure is apparent within one or two days. Rejection usually starts at the end of the first week. There may be problems like bleeding of the bile duct after surgery, or blood vessels of the liver may become too narrow. The surgery itself may need revision because of narrowing, leaking, or blood clots at the connections. These issues may be solved with or without more surgery depending on the severity.

Infections are a constant risk while on immunosuppressive agents, because the immune system is supposed to prevent them. A method has not yet been devised to control rejection without hampering immune

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

A transplant surgeon will perform the surgery in a hospital that has a special unit called a transplant center.

defenses against infections. Not only do ordinary infections pose a threat, but because of the impaired immunity, transplant patients are susceptible to the same opportunistic infections (OIs) that threaten acquired immune deficiency syndrome (AIDS) patients–pneumocystis pneumonia, herpes and cytomegalovirus (CMV) infections, fungi, and a host of bacteria.

Drug reactions are also a continuing threat. Every drug used to suppress the immune system has potential problems. As previously stated, hypertension, nephrotoxicity, and PTLD are some of the long-term adverse effects with immunosupressive drugs like cyclosporine. Immunosuppressants also hinder the body’s ability to resist cancer. All drugs used to prevent rejection increase the risk of leukemias and lymphomas.

There is also a risk of the original disease returning. In the case of hepatitis C, reoccurrence is a risk factor for orthotropic liver transplants. Newer antiviral drugs hold out promise for dealing with hepatitis. In alcoholics, the urge to drink alcohol will still be a problem. Alcoholics Anonymous (AA) is the most effective treatment known for alcoholism.

Transplant recipients can get high blood pressure, diabetes, high cholesterol, thinning of the bones, and can become obese. Close medical care is needed to prevent these conditions.

Normal results

For a successful transplant, good medical care is important. Patients and families must stay in touch with their medical teams and drugs must be taken as advised to prevent infection and rejection of the new organ. However, sometimes because of the way it is preserved, the new liver doesn’t function as it should, and a patient may have to go back on to the waiting list to receive a new liver.

Morbidity and mortality

Twenty-five million or one in 10 Americans are or have been afflicted with liver or biliary diseases. As of July 1, 2006, there were 17,298 patients on the UNOS

QUESTIONS TO ASK THE DOCTOR

• What should I do to prepare for this operation?
• Who will tell me about the transplant process?
• Can I tour the transplant center?
• Who are the members of the transplant team and what are their jobs?
• Is there a special nursing unit for transplant patients?
• How many attending surgeons are available to do my type of transplant?
• Does the hospital do living donor transplants?
• Is a living donor transplant a choice in my case? If so, where will the living donor evaluation be done?
• What is the organ recovery cost if I have a living donor?
• Will I also need to change my lifestyle?
• How long will I have to stay in the hospital?
• Why is recovery such a slow process?

National Transplant Waiting List who were waiting for a liver transplantation. During the year running from July 2006 to July 2007, 6,532 liver transplants were performed. Of these, 6,274 were deceased donor transplants, and 258 were living donor transplants. For liver transplants performed from July 1, 1999 through June 30, 2001, the one-year survival rate was 86% for adults; 1,861 patients died while on the UNOS waiting list for the year ending June 30, 2002. More than 80% of children survive transplantation to adolescence and adulthood.

Since the introduction of cyclosporine and tacrolimus (drugs that suppress the immune response and keep it from attacking and damaging the new liver), success rates for liver transplantation have reached 80-90%.

Infections occur in about half of transplant patients and often appear during the first week. Biliary complications are apparent in about 22% of recipient patients (and 6% of donors), and vascular complications occur in 9.8% of recipient patients. Other complications in donors include re-operation (4.5%) and death (0.2%).

There are potential social, economic, and psychological problems, and a vast array of possible medical and surgical complications. Close medical surveillance must continue for the rest of the patient’s life.

Alternatives

There is no treatment that can help the liver with all of its functions; thus, when a person reaches a certain stage of liver disease, a liver transplant may be the only way to save the patient’s life.

Resources

BOOKS

Abhinav, Humar, M.D., I. Hertz Marshall, M.D., Laura J., Blakemore, M.D., eds. Manual of Liver Transplant Medical Care. Minneapolis, MN: Fairview Press, 2002.

Feldman, M, et al.. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. 8th ed. St. Louis: Mosby, 2005.

Khatri, VP and JA Asensio. Operative Surgery Manual. 1st ed. Philadelphia: Saunders, 2003.

Townsend, CM et al. Sabiston Textbook of Surgery. 17th ed. Philadelphia: Saunders, 2004.

PERIODICALS

Brown, R.S., Jr., M. W. Russo, M. Lai, M. L. Shiffman, M. C. Richardson, J. E. Everhart, et al. “A survey of liver transplantation from living adult donors in the United States.” New England Journal of Medicine 348, no. 9 (February, 2003):818–25.

Goldstein, M. J., E. Salame, S. Kapur, M. Kinkhabwala, D. LaPointe-Rudow, N. P. P. Harren, et al. “Analysis of failure in living donor liver transplantation: differential outcomes in children and adults.” World Journal of Surgery 27, no. 3 (2003):356–64.

Kelly, D. A. “Strategies for optimizing immunosuppression in adolescent transplant recipients: a focus on liver transplantation.” Paediatric Drugs 5, no. 3 (2003): 177–83.

Longheval, G., P. Vereerstraeten, P. Thiry, M. Delhaye, O. Le Moine, J. Deviere, et al. “Predictive models of short-and long-term survival in patients with nonbiliary cirrhosis.” Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 9, no. 3 (March, 2003):260–7.

Neff, G. W., A. Bonham, A. G. Tzakis, M. Ragni, D. Jayaweera, E. R. Schiff, et al. “Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease.” Liver Transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 9, no. 3 (March, 2003): 239–47.

Papatheodoridis, G. V., V. Sevastianos, and A. K. Burrouhs. “Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era.” American Journal of Transplantation 3, no. 3 (March, 2003):250–8.

ORGANIZATIONS

American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY. 10038. (800) 465-4837 or (888) 443-7872. Fax: (212) 483.8179. E-mail: info@liverfoundation.org. http://www.liverfoundation.or

Hepatitis Foundation International (HFI). 504 Blick Drive, Silver Spring, MD. 20904-2901. (800) 891-0707 or (301) 622-4200. Fax: (301) 622-4702. Email: hfi@comcast.net. http://www.hepfi.org

National Digestive Diseases, Information Clearinghouse. 2 Information Way, Bethesda, MD. 20892-3570. Email:nddic@info.niddk.nih.gov.

National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland. 20892. (301) 496-4000. Email: NIHInfo@OD.NIH.GOV. http://www.nih.gov.

United Network for Organ Sharing. 500-1100 Boulders Parkway, P.O. Box 13770. Richmond, VA. 23225. (888) 894-6361 or (804) 330-8500. http://www.unos.org

OTHER

U.S. National Library of Medicine and the National Institutes of Health. Liver Transplantation. 2003. [cited March 13, 2003]. www.nlm.nih.gov/medlineplus/livertransplantation.html.

J. Ricker Polsdorfer, M.D.

Crystal H. Kaczkowski, M.Sc.

Rosalyn Carson-DeWitt, MD

Liver transplantation

Definition

Liver transplantation is a surgery that removes a diseased liver and replaces it with a healthy donor liver.

Purpose

A liver transplant is needed when the liver's function is reduced to the point that the life of the patient is threatened.

Demographics

Compared to whites, those with African-American, Asian, Pacific Islander, or Hispanic descent are three times more likely to suffer from end-stage renal disease (ESRD). Both children and adults can suffer from liver failure and require a transplant.

Patients with advanced heart and lung disease, who are human immunodeficiency virus (HIV) positive, and who abuse drugs and alcohol are poor candidates for liver transplantation. Their ability to survive the surgery and the difficult recovery period, as well as their long-term prognosis, is hindered by their conditions.

Description

The liver is the body's principle chemical factory. It receives all nutrients, drugs, and toxins, which are absorbed from the intestines, and performs the final stages of digestion, converting food into energy and replacement parts for the body. The liver also filters the blood of all waste products, removes and detoxifies poisons, and excretes many of these into the bile. It further processes other chemicals for excretion by the kidneys. The liver is also an energy storage organ, converting food energy to a chemical called glycogen that can be rapidly converted to fuel.

When other medical treatment interferes with the functioning of a damaged liver, a transplant is necessary. Since 1963, when the first human liver transplant was performed, thousands more have been performed each year. Cirrhosis, a disease that kills healthy liver cells, replacing them with scar tissue, is the most common reason for liver transplantation in adults. The most frequent reason for transplantation in children is biliary atresia—a disease in which the ducts that carry bile out of the liver, are missing or damaged.

Included among the many causes of liver failure that bring patients to transplant surgery are:

• Progressive hepatitis, mostly due to virus infection, accounts for more than one-third of all liver transplants.
• Alcohol damage accounts for approximately 20% of transplants.
• Scarring, or abnormality of the biliary system, accounts for roughly another 20% of liver transplants.
• The remainder of transplants come from various cancers, uncommon diseases, and a disease known as fulminant liver failure.

Fulminant liver failure most commonly happens during acute viral hepatitis, but is also the result of mushroom poisoning by Amanita phalloides and toxic reactions to overdose of some medicines, such as acetaminophen—a medicine commonly used to relieve pain and reduce fever. The person who is the victim of mushroom poisoning is a special category of candidate for a liver transplant because of the speed of the disease and the immediate need for treatment.

As the liver fails, all of its functions diminish. Nutrition suffers, toxins build, and waste products accumulate. Scar tissue accumulates on the liver as the disease progresses. Blood flow is increasingly restricted in the portal vein, which carries blood from the stomach and abdominal organs to the liver. The resulting high blood pressure (hypertension) causes swelling of and bleeding from the blood vessels of the esophagus. Toxins build-up in the blood (liver encephalopathy), resulting in severe jaundice (yellowing of the skin and eyes), fluid accumulation in the abdomen (ascites), and deterioration of mental function. Eventually, death occurs.

There are three types of liver transplantation methods. They include:

• Orthotopic transplantation, the replacement of a whole diseased liver with a healthy donor liver.
• Heterotrophic transplantation, the addition of a donor liver at another site, while the diseased liver is left intact.
• Reduced-size liver transplantation, the replacement of a whole diseased liver with a portion of a healthy donor liver. Reduced-size liver transplants are most often performed on children.

When an orthotropic transplantation is performed, a segment of the inferior vena cava (the body's main vein to the heart) attached to the liver is taken from the donor, as well. The same parts are removed from the recipient and replaced by connecting the inferior vena cava, the hepatic artery, the portal vein, and the bile ducts.

When there is a possibility that the afflicted liver may recover, a heterotypic transplantation is performed. The donor liver is placed in a different site, but it still has to have the same connections. It is usually attached very close to the patient's original liver; if the original liver recovers, the donor liver will wither away. If the patient's original liver does not recover, that liver will dry up, leaving the donor in place.

Reduced-size liver transplantation puts part of a donor liver into a patient. A liver can actually be divided into eight pieces—each supplied by a different set of blood vessels. In the past, just two of these sections have been enough to save a patient suffering from liver failure, especially if it is a child. It is possible, therefore, to transplant one liver into at least two patients and to transplant part of a liver from a living donor—and for both the donor and recipients to survive. Liver tissue grows to accommodate its job provided that the organ is large enough initially. Patients have survived with only 15–20% of their original liver intact, assuming that that portion was healthy from the beginning.

As of 2003, the availability of organs for transplant was in crisis. In October 1997, a national distribution system was established that gives priority to patients who are most ill and in closest proximity to the donor livers. Livers, however, are available nationally. It is now possible to preserve a liver out of the body for 10 to 20 hours by flushing it with cooled solutions of special chemicals and nutrients, if necessary. This enables transport cross-country.

Description

Once a donor liver has been located and the patient is in the operating room and under general anesthesia, the patient's heart and blood pressure are monitored. A long cut is made alongside of the ribs; sometimes, an upwards cut may also be made. When the liver is removed, four blood vessels that connect the liver to the rest of the body are cut and clamped shut. After getting the donor liver ready, the transplant surgeon connects these vessels to the donor vessels. A connection is made from the bile duct (a tube that drains the bile from the liver) of the donor liver to the bile duct of the liver of the patient's bile duct. In some cases, a small piece of the intestine is connected to the new donor bile duct. This connection is called Roux-en-Y. The operation usually takes between six and eight hours; another two hours is spent preparing the patient for surgery. Therefore, a patient will likely be in the operating room for eight to 10 hours.

The United Network for Organ Sharing (UNOS) data indicates that patients in need of organ transplants outnumber available organs three to one.

Diagnosis/Preparation

The liver starts to fail only when more than half of it is damaged. Thus, once a person demonstrates symptoms of liver failure, there is not much liver function left. Signs and symptoms of liver failure include:

• jaundice
• muscle wasting (loss of muscle)
• forgetfulness, confusion, or coma
• fatigue
• itching
• poor blood clotting
• build-up of fluid in the stomach (ascites)
• infections
• bleeding in the stomach

A doctor will diagnose liver disease; a liver specialist, a transplant surgeon, and other doctors will have to be consulted, as well, before a patient can be considered for a liver transplant. Before transplantation takes place, the patient is first determined to be a good candidate for transplantation by going through a rigorous medical examination. Blood tests, consultations, and x rays will be needed to determine if the patient is a good candidate. Other tests that may be conducted are: computed tomography (CAT or CT) scan, magnetic resonance image (MRI), ultrasound, routine chest x ray , endoscopy, sclerotherapy and rubber-band ligation, transjugular intrahepatic portosystemic shunt (TIPS), creatinine clearance, cardiac testing (echocardiogram [ECHO]) and/or electrocardiogram [EKG or ECG]), and pulmonary function test [PFTs]), liver biopsy , and nutritional evaluation. A dietitian will evaluate the patient's nutritional needs and design an eating plan. Since a patient's emotional state is as important as their physical state, a psychosocial evaluation will be administered.

Once test results are reviewed and given to the liver transplant selection committee, the patient will be assessed for whether he or she is an appropriate candidate. Some patients are deemed too healthy for a transplant and will be followed and retested at a later date if their liver gets worse. Other patients are determined to be too sick to survive a transplant. The committee will not approve a transplant for these patients. Once a patient is approved, they will be placed on a waiting list for a donor liver. When placed on the waiting list, a patient will be given a score based on the results of the blood tests. The higher a patient's score, the sicker the patient is. This results in the patient earning a higher place on the waiting list.

Suitable candidates boost their nutritional intakes to ensure that they are as healthy as possible before surgery. Drugs are administered that will decrease organ rejection after surgery. The medical committee consults with the patient and family, if available, to explain the surgery and any potential complications. Many problems can arise during the waiting period. Medicines should be changed as needed, and blood tests should be done to assure a patient is in the best possible health for the transplant surgery. Psychological counseling during this period is recommended, as well.

When a donor is found, it is important that the transplant team be able to contact the patient. The patient awaiting the organ must not eat or drink anything from the moment the hospital calls. On the other hand, the liver may not be good enough for transplantation. Then, the operation will be cancelled, although this does not happen often.

Aftercare

Following surgery, the patient will wake up in the surgical intensive care unit (SICU). During this time, a tube will be inserted into the windpipe to facilitate breathing. It is removed when the patient is fully awake and strong enough to breathe on his or her own. There may be other tubes that are removed as the patient recovers. When safe to leave the SICU, the patient is moved to the transplant floor. Walking and eating will become the primary focus. Physical therapy may be started to help the patient become active, as it is an important part of recovery. When the patient begins to feel hungry and the bowels are working, regular food that is low in salt will be given.

A patient should expect to spend about 10 to 14 days in the hospital, although some stays may be shorter or longer. Before leaving the hospital, a patient will be advised of: signs of infection or rejection, how to take medications and change dressings, and how to understand general health problems. Infection can be a real danger, because the medications taken compromise the body's defense systems. The doctors will conduct blood tests, ultrasounds, and x rays to ensure that the patient is doing well.

The first three months after transplant are the most risky for getting such infections as the flu, so patients should follow these precautions:

• Avoid people who are ill.
• Wash hands frequently.
• Tell the doctor if you are exposed to any disease.
• Tell the doctor if a cold sore, rash, or water blister appears on the body or spots appear in the throat or on the tongue.
• Stay out of crowds and rooms with poor circulation.
• Do not swim in lakes or community pools during the three months following transplant.
• Eat meats that are well-cooked.
• Stay away from soil, including those in which house-plants are grown, and gardens, during the three months following transplant.
• Take all medications as directed.
• Learn to report the early symptoms of infection.

To ensure that the transplant is successful and that the patient has a long and healthy life, a patient must get good medical care, prevent and treat complications, keep in touch with doctors and nurses, and follow their advice. Nutrition plays a big part in the success of a liver transplant, so what a patient eats after the transplant is very important.

Medications needed following liver transplantation

Successfully receiving a transplanted liver is only the beginning of a lifelong process. Patients with transplanted livers have to stay on immunosuppressant drugs for the rest of their lives to prevent organ rejection. Although many patients can reduce the dosage after the initial few months, virtually none can discontinue drugs altogether. For adolescent transplant recipients, post transplantation is a particularly difficult time, as they must learn to take responsibility for their own behavior and medication, as well as balance their developing sexuality in a body that has been transformed by the adverse effects of immuno-suppression. Long-term outcome and tailoring of immunosuppression is of great importance.

Cyclosporine has long been the drug of experimentation in the immunosuppression regimen, and has been well-tolerated and effective. Hypertension, nephrotoxicity, and posttransplant lymphoproliferative disease (PTLD) are some of the long-term adverse effects. Tacrolimus has been developed more recently, and has improved the cosmetic adverse effects of cyclosporine, but has similar rates of hypertension and nephrotoxicity, and possibly a higher rate of PTLD. Prednisone, azathioprine, and tacrolimus are often combined with cyclosporine for better results. Newer immunosuppressive agents promise even better results.

There has been a recent, welcome development in renal sparing drugs, such as mycophenolate mofetil, which has no cosmetic adverse effects, does not require drug level monitoring, and is thus particularly attractive to teenagers. If started prior to irreversible renal dysfunction, recent research demonstrates recovery of renal function with mycophenolate mofetil. There is little published data on the use of sirolimus (rapamycin) in the pediatric population, but preliminary studies suggest that the future use of interleukin-2 receptor antibodies may be beneficial for immediate post-transplant induction of immunosuppression. When planning immunosuppression for adolescents, it is important to consider the effects of drug therapy on both males and females in order to maintain fertility and to ensure safety in pregnancy. Adequate practical measures and support should reduce noncompliance in this age group, and allow good, long-term function of the transplanted liver.

Risks

Early failure of the transplant occurs in every one in four surgeries and has to be repeated. Some transplants never work, some patients succumb to infection, and some suffer immune rejection. Primary failure is apparent within one or two days. Rejection usually starts at the end of the first week. There may be problems like bleeding of the bile duct after surgery, or blood vessels of the liver may become too narrow. The surgery itself may need revision because of narrowing, leaking, or blood clots at the connections. These issues may be solved with or without more surgery depending on the severity.

Infections are a constant risk while on immunosuppressive agents, because the immune system is supposed to prevent them. A method has not yet been devised to control rejection without hampering immune defenses against infections. Not only do ordinary infections pose a threat, but because of the impaired immunity, transplant patients are susceptible to the same opportunistic infections (OIs) that threaten acquired immune deficiency syndrome (AIDS) patients—pneumocystis pneumonia, herpes and cytomegalovirus (CMV) infections, fungi, and a host of bacteria.

Drug reactions are also a continuing threat. Every drug used to suppress the immune system has potential problems. As previously stated, hypertension, nephrotoxicity, and PTLD are some of the long-term adverse effects with immunosupressive drugs like cyclosporine. Immunosuppressants also hinder the body's ability to resist cancer. All drugs used to prevent rejection increase the risk of leukemias and lymphomas.

There is also a risk of the original disease returning. In the case of hepatitis C, reoccurrence is a risk factor for orthotropic liver transplants. Newer antiviral drugs hold out promise for dealing with hepatitis. In alcoholics, the urge to drink alcohol will still be a problem. Alcoholics Anonymous (AA) is the most effective treatment known for alcoholism.

Transplant recipients can get high blood pressure, diabetes, high cholesterol, thinning of the bones, and can become obese. Close medical care is needed to prevent these conditions.

Normal results

For a successful transplant, good medical care is important. Patients and families must stay in touch with their medical teams and drugs must be taken as advised to prevent infection and rejection of the new organ. However, sometimes because of the way it is preserved, the new liver doesn't function as it should, and a patient may have to go back on to the waiting list to receive a new liver.

Morbidity and mortality

Twenty-five million or one in 10 Americans are or have been afflicted with liver or biliary diseases. As of June 2003, there were 17,239 patients on the UNOS National Transplant Waiting List who were waiting for a liver transplantation. For the previous year (July 1, 2001 to June 30, 2002), there were a total of 5,261 liver transplants performed. Of those, 4,785 were cadaver donors (already deceased) and 476 living donors. For liver transplants performed from July 1, 1999 to June 30, 2001, the one-year survival rate was 86% for adults; 1,861 patients died while on the UNOS waiting list for the year ending June 30, 2002. More than 80% of children survive transplantation to adolescence and adulthood.

Since the introduction of cyclosporine and tacrolimus (drugs that suppress the immune response and keep it from attacking and damaging the new liver), success rates for liver transplantation have reached 80–90%.

Infections occur in about half of transplant patients and often appear during the first week. Biliary complications are apparent in about 22% of recipient patients (and 6% of donors), and vascular complications occur in 9.8% of recipient patients. Other complications in donors include re-operation (4.5%) and death (0.2%).

There are potential social, economic, and psychological problems, and a vast array of possible medical and surgical complications. Close medical surveillance must continue for the rest of the patient's life.

Alternatives

There is no treatment that can help the liver with all of its functions; thus, when a person reaches a certain stage of liver disease, a liver transplant may be the only way to save the patient's life.

Resources

books

Abhinav, Humar, M.D., I. Hertz Marshall, M.D., Laura J., Blakemore, M.D., eds. Manual of Liver Transplant Medical Care. Minneapolis, MN: Fairview Press, 2002.

Beauchamp, Daniel R., M.D., Mark B. Evers, M.D., Kenneth L. Mattox, M.D., Courtney M. Townsend, and David C. Sabiston, eds. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 16th ed. London: W. B. Saunders Co., 2001.

Lawrence, Peter F., Richard M. Bell, and Merril T. Dayton, eds. Essentials of General Surgery, 3rd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2000.

periodicals

Brown, R.S., Jr., M. W. Russo, M. Lai, M. L. Shiffman, M. C. Richardson, J. E. Everhart, et al. "A survey of liver transplantation from living adult donors in the United States." New England Journal of Medicine 348, no. 9 (February, 2003):818–25.

Goldstein, M. J., E. Salame, S. Kapur, M. Kinkhabwala, D. La-Pointe-Rudow, N. P. P. Harren, et al. "Analysis of failure in living donor liver transplantation: differential outcomes in children and adults." World Journal of Surgery 27, no. 3 (2003):356–64.

Kelly, D. A. "Strategies for optimizing immunosuppression in adolescent transplant recipients: a focus on liver transplantation." Paediatric Drugs 5, no. 3 (2003):177–83.

Longheval, G., P. Vereerstraeten, P. Thiry, M. Delhaye, O. Le Moine, J. Deviere, et al. "Predictive models of short- and long-term survival in patients with nonbiliary cirrhosis." Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 9, no. 3 (March, 2003):260–7.

Neff, G. W., A. Bonham, A. G. Tzakis, M. Ragni, D. Jayaweera, E. R. Schiff, et al. "Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease." Liver Transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 9, no. 3 (March, 2003):239–47.

Papatheodoridis, G. V., V. Sevastianos, and A. K. Burrouhs. "Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era." American Journal of Transplantation 3, no. 3 (March, 2003):250–8.

Rudow, D. L., M. W. Russo, S. Haflige, J. C. Emond, and R. S. Brown, Jr. "Clinical and ethnic differences in candidates listed for liver transplantation with and without potential living donors." Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 9, no. 3 (March, 2003):254–9.

Wong, F. "Liver and kidney diseases." Clinics in Liver Disease 6, no. 4 (November, 2002):981–1011.

organizations

American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY. 10038. (800) 465-4837 or (888) 443-7872. Fax: (212) 483.8179. info@liverfoundation.org. <http://www.liverfoundation.org>.

Hepatitis Foundation International (HFI). 504 Blick Drive, Silver Spring, MD. 20904-2901. (800) 891-0707 or (301) 622-4200. Fax: (301) 622-4702. hfi@comcast.net. <http://www.hepfi.org>

National Digestive Diseases, Information Clearinghouse. 2 Information Way, Bethesda, MD. 20892-3570. nddic@info.niddk.nih.gov.

National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland. 20892. (301) 496-4000. NIHInfo@OD.NIH.GOV. <http://www.nih.gov.>

United Network for Organ Sharing. 500-1100 Boulders Parkway, P.O. Box 13770. Richmond, VA. 23225. (888) 894-6361 or (804) 330-8500. <http://www.unos.org>

other

U.S. National Library of Medicine and the National Institutes of Health. Liver Transplantation. 2003 [cited March 13, 2003]. <www.nlm.nih.gov/medlineplus/livertransplantation.html>.

J. Ricker Polsdorfer, M.D.
Crystal H. Kaczkowski, M.Sc.

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

A transplant surgeon will perform the surgery in a hospital that has a special unit called a transplant center.

QUESTIONS TO ASK THE DOCTOR

• What should I do to prepare for this operation?
• Who will tell me about the transplant process?
• Can I tour the transplant center?
• Who are the members of the transplant team and what are their jobs?
• Is there a special nursing unit for transplant patients?
• How many attending surgeons are available to do my type of transplant?
• Does the hospital do living donor transplants?
• Is a living donor transplant a choice in my case? If so, where will the living donor evaluation be done?
• What is the organ recovery cost if I have a living donor?
• Will I also need to change my lifestyle?
• How long will I have to stay in the hospital?
• Why is recovery such a slow process?

Liver Transplantation

Definition

Liver transplantation is a surgery that removes a diseased liver and replace it with a healthy donor liver.

Purpose

The liver is the body's principle chemical factory. It receives all nutrients, drugs, and toxins absorbed from the intestines and performs the final stages of digestion, converting food into energy and replacement parts for the body. The liver also filters the blood of all waste products, removes and detoxifies poisons and excretes many of these into the bile. It processes other chemicals for excretion by the kidneys. The liver is also an energy storage organ, changing food energy to a chemical called glycogen that can be rapidly converted to fuel.

As the liver fails, all of its functions diminish. Nutrition suffers, toxins build up, and waste products accumulate. Scar tissue builds up on the liver if disease is of long duration. As the liver scars, blood flow is progressively restricted in the portal vein, which carries blood from the stomach and abdominal organs to the liver. The resulting high blood pressure (hypertension ) causes swelling of and bleeding from the blood vessels of the esophagus. Severe jaundice, fluid accumulation in the abdomen (ascites ), and deterioration of mental function, due to the build-up of toxins in the blood (liver encephalopathy ), eventually occur, leading to death.

Among the many causes of liver failure that bring patients to transplant surgery are:

• Progressive hepatitis (mostly due to virus infection) accounts for more than a third.
• Alcohol damage brings in about 20%
• Scarring or abnormality of the biliary system accounts for roughly another 20%.
• The remainder comes from selected cancers, other uncommon diseases, and a situation called fulminant liver failure.

Fulminant liver failure most commonly happens during acute viral hepatitis, but it is also the result of mushroom poisoning by Amanita phalloides and toxic reactions to some medicines, like an overdose of acetaminophen. This is a special category of candidates for liver transplant because of the speed of their disease and the immediate need of treatment.

The first human liver transplant was performed in 1963, and since then, thousands of liver transplants are done every year. Since the introduction of of cyclosporine (a drug that suppresses the immune response that rejects the donor organ), success rates for liver transplantation have reached 85%.

Precautions

Patients with advanced heart and lung disease, who are HIV positive, and who abuse drugs and alcohol are poor candidates for liver tranplantation. Their ability to survive the surgery and the difficult recovery period, as well as their longterm prognosis, is hindered by their conditions.

Description

There are three types of liver transplantation methods. They include:

• Orthotopic transplantation is the replacement of a whole diseased liver with a healthy donor liver.
• Heterotopic transplantation is the addition of a donor liver at another site, while the diseased liver is left intact.
• Reduced-size liver transplantation is the replacement of a whole diseased liver with a portion of a healthy donor liver. Reduced-size liver transplants are most often performed on children.

When an orthotopic transplantation is performed, a segment of the inferior vena cava attached to the liver is taken from the donor as well. The same parts are removed from the recipient and replaced by connecting the inferior vena cava, the hepatic artery, the portal vein and the bile ducts.

When there is a possibility that the afflicted liver may recover, a heterotopic tranplantation is performed. The donor liver is placed in a different site, but it still has to have the same connections. It is usually attached very near the original liver, and if the original liver recovers, the donor shrivels away. If the original liver does not recover, it will shrivel, leaving the donor in place.

Reduced-size liver transplantation tranplants part of a donor liver into a patient. It is possible to divide the liver into eight pieces, each supplied by a different set of blood vessels. Two of these pieces have been enough to save a patient in liver failure, especially if the patient is a child. It is therefore possible to transplant one liver into at least two patients and to transplant part of a liver from a living donor and have both donor and recipient survive. Liver tissue grows to accommodate its job so long as there is initially enough of the organ to use. Patients have survived with only 15-20% of their original liver, provided that 15-20% was healthy.

Availability of organs for transplant is a current crisis in the transplantation business. In October 1997, a national distribution system was established that gives priority to the sickest patients closest in location to the donor liver, but makes livers available nationally. It is now possible to preserve a liver out of the body for 10-20 hours by flushing it with cooled solutions of special chemicals and nutrients, so it can be transported across the country.

Preparation

Before transplantation takes place, the patient is first determined to be a good candidate for transplantation by going through rigorous medical examination. A suitable candidate boosts their nutritional intake in order to ensure that they are as healthy as possible before surgery. Drugs are administered that will decrease rejection after surgery. Consultation with the patient, as well as any family, is conducted to explain the surgery and its complications. Psychological counciling is recommended.

Aftercare

In order to prevent organ rejection, immunosuppressive drugs will be taken. Hospitalization ranges from four weeks to five months, depending on the rate of recovery.

Successfully receiving a transplanted liver is only the beginning of a life-long process. Patients with transplanted livers have to stay on immunosuppressant drugs for the rest of their lives to prevent organ rejection. Although many can reduce the dosage after the initial few months, virtually none can discontinue drugs altogether. Prednisone, azathioprine, and tacrolimus are often combined with cyclosporine for better results. Newer immunosuppressive agents are coming that promise even better results. In spite of immunosuppressants, rejection occurs most of the time and requires additional medication. In some cases it cannot be reversed, and retransplantation becomes necessary.

Risks

Early failure of the transplant occurs once in four surgeries and has to be repeated. Some transplants never work, some succumb to infection, and some suffer immune rejection. Primary failure is apparent within one or two days. Infections happen in half the patients and often appear during the first week. Rejection usually starts at the end of the first week. The surgery itself may need revision because of narrowing, leaking, or blood clots at the connections.

There are potential social and economic problems, psychological problems, and a vast array of possible medical and surgical complications. Close medical surveillance must continue for the rest of the patient's life. Infections are a constant risk while on immunosuppressive agents, because the immune system is supposed to prevent them. A way has not yet been devised to control rejection without hampering immune defenses against infections. Not only do ordinary infections pose a threat, but because of the impaired immunity, transplant patients are susceptible to the same "opportunistic" infections that threaten AIDS patients—pneumocystis pneumonia, herpes and cytomegalovirus infections, fungi, and a host of bacteria.

Immunosuppression also hinders the body's ability to resist cancer. All the drugs used to prevent rejection increase the risk of leukemias and lymphomas.

There is also a risk of the original disease returning. Hepatitis virus still inhabits the patient, as does the urge to drink alcohol. Newer antiviral drugs hold out promise for dealing with hepatitis, and Alcoholics Anonymous (AA) is the most effective treatment known for alcoholism.

Drug reactions are also a continuing threat. Every drug used to suppress the immune system has potential problems.

Resources

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 223-0179. 〈http://www.liverfoundation.org〉.

KEY TERMS

Acetaminophen— A common pain reliever (Tylenol).

Antigen— Any chemical that provokes an immune response.

Bile ducts— Tubes carrying bile from the liver to the intestines.

Biliary system— The tree of tubes that carries bile.

Hepatic artery— The blood vessel supplying arterial blood to the liver.

Inferior vena cava— The biggest vein in the body, returning blood to the heart from the lower half of the body.

Leukemia— A cancer of the white blood cells.

Lymphoma— A cancer of lymphatic tissue.

Portal vein— The blood vessel carrying venous blood from the abdominal organs to the liver.