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National Digestive Diseases Information Clearinghouse

What is liver Who needs a ? transplant? Liver transplantation is to remove People with either acute or chronic liver fail- U.S. Department a diseased or injured liver and replace it ure may need a liver transplant to survive. of Health and with a healthy whole liver or a segment of a Services • � (ALF) happens sud- liver from another person, called a donor. denly. Drug-induced (DILI) A successful liver transplant is a life-saving NATIONAL is the leading cause of ALF in the treatment for people with liver failure, a INSTITUTES United States. The most common cause OF HEALTH condition in which the liver no longer works of DILI is an overdose of acetamino- as it should. phen (Tylenol). • � Chronic liver failure, also called end- stage , progresses over What does the liver do? months, years, or decades. Most often, The body’s largest internal organ, the chronic liver failure is the result of cir- liver has many important functions rhosis, a condition in which scar tissue including replaces healthy liver tissue until the liver cannot function adequately. • preventing In U.S. adults, the most common reason for • removing bacteria and toxins from needing a liver transplant is caused the blood by chronic C, followed by cirrhosis • controlling immune responses caused by long-term alcohol abuse. Many other liver diseases also cause cirrhosis, • processing nutrients, medications, including and hormones • � other forms of chronic hepatitis, includ- • making proteins that help the ing chronic and autoimmune blood clot hepatitis • producing bile, which helps the • � diseases that affect the bile ducts— body absorb fats—including tubes that carry bile from the liver to cholesterol—and fat-soluble vitamins the and — • storing vitamins, minerals, fats, and including , Alagille syn- sugars for use by the body drome, primary biliary cirrhosis, and primary sclerosing cholangitis A healthy liver is necessary for survival. A healthy liver can regenerate most of its own cells when they become damaged. • � hemochromatosis, a genetic condition in • � passing black stools which iron builds up in the liver • � , the buildup of fluid in the • � Wilson disease, a genetic condition in abdomen which copper builds up in the liver • � forgetfulness or confusion • � nonalcoholic steatohepatitis, or NASH, a disease caused by fat and inflamma- What is the process for tion in the liver getting a liver transplant? In children, biliary atresia is the most com- The process for getting a liver transplant mon cause of liver failure and the need for a begins with a referral by a doctor to a trans- liver transplant. Biliary atresia is a disease in plant center. People seeking a liver trans- newborns in which the bile ducts are absent, plant are carefully evaluated by a team at the damaged, or blocked. As a result, toxic bile transplant center to determine whether they builds up in the liver, resulting in cirrhosis. are suitable candidates for transplantation. Other reasons for liver transplantation The evaluation includes a complete medi- include cancers originating in the liver such cal history, physical examination, blood and as , hepatoblas- urine tests, x rays and other imaging tests, toma, and . and tests to check the function of the heart, lungs, and kidneys. The transplant team usually includes liver transplant surgeons; What are the signs and liver specialists, called hepatologists; nurses; symptoms of liver failure? transplant coordinators; social workers; a The signs and symptoms of liver failure may psychiatrist; and other specialists. A finan- include cial counselor may help with making arrange- ments to pay for the transplant. • � jaundice, a condition that causes yellow- ing of the skin and the whites of the eyes The evaluation of a transplant candidate typically includes assessment of • � fatigue • � the status of the person’s liver disease • � weakness • � other diseases and conditions the per- • � loss of appetite son has • � nausea • � the likelihood the person will survive • � weight loss the transplant operation • � muscle loss • � the person’s ability to follow instruc- • � itching tions and the complex medical regimen required after a transplant • � bruising or bleeding easily because blood does not clot � • � the person’s mental and emotional health � • � bleeding in the • � the person’s support system • � vomiting blood

2 � Liver Transplantation A liver transplant selection committee Scoring Systems reviews the results of the evaluation, deter- When people are registered on the waiting mines whether the person meets the trans- list, they are assigned a score that indicates plant center’s criteria for a transplant, and how urgently they need a transplant. The decides whether to register the person on the two scoring systems are the Model for End- national waiting list for a transplant. stage Liver Disease (MELD) scoring system, The national waiting list is maintained by the used for people age 12 and older, and the United Network for Organ Sharing (UNOS), Pediatric End-stage Liver Disease (PELD) which administers the U.S. Organ Procure- scoring system, used for children younger ment and Transplantation Network (OPTN) than 12. under contract with the Health Resources MELD and PELD scores are calculated by and Services Administration (HRSA) of computer using the results of blood tests. the U.S. Department of Health and Human MELD scores range from 6 to 40. PELD Services. scores can range from negative numbers to Not everyone sent to the transplant center is 99. These scores are used to estimate the advised to have a transplant, and not every likelihood of dying within the next 90 days person who starts an evaluation is placed on without a transplant. A higher score indi- the transplant list. While undergoing evalu- cates a more urgent need for a liver trans- ation, and while waiting for a transplant, plant. While patients are on the national list patients should take care of their health. wait for a transplant, their MELD or PELD score may go up if their condition worsens or Even if the liver transplant selection com- go down if their condition improves. mittee approves a candidate for a transplant, he or she may choose not to proceed with it. The MELD score is calculated using the To ensure the person can make an informed results of three blood tests: decision about having a transplant, the trans- • � bilirubin, which tests the amount of bile plant team provides information about the pigment in the blood • selection process for transplantation • � creatinine, which tests kidney function • operation and recovery • � international normalized ratio (INR), • � long-term demands of living with a liver which tests the blood’s ability to clot transplant The MELD score calculation also considers whether a patient who has poor kidney func- tion is on dialysis.

3 � Liver Transplantation The PELD score is calculated based on What might prevent a • the results of blood tests for bilirubin, person from having a liver INR, and albumin, the major protein in transplant? the blood Each transplant center has its own guidelines • the child’s degree of growth failure regarding eligibility for liver transplantation. • the child’s age at time of registration A center might determine that a person with acute or chronic liver failure is not a candi- The MELD and PELD scoring systems have date for a liver transplant if the person has been in place since early 2002 and have helped reduce the size of the waiting list and • cancer outside the liver the amount of time a person has to wait to • throughout the body receive a transplant. The MELD and PELD scoring systems continue to be studied to see • advanced heart or lung disease whether adding other factors in the calcu- • an alcohol or drug abuse problem lations can increase the ability to predict • AIDS the risk of death without a transplant. The UNOS uses MELD and PELD scores in allo- • the inability to follow a treatment cating for transplantation to patients regimen on the national waiting list. More informa- • a lack of psychosocial support tion about the MELD and PELD scoring systems is available from the UNOS at www. In addition, the transplant candidate may unos.org/resources/meldPeldCalculator.asp decide not to go forward with a transplant. and www.unos.org/SharedContentDocuments/ MELD_PELD(1).pdf. Status 1 Patients Critically ill patients with acute liver fail- ure who are likely to die within a week are categorized as status 1 patients and are given highest priority for liver transplantation.

4 Liver Transplantation Where do donated livers A small number of liver transplants are performed using living donors. Most living come from? donors are relatives of the recipient. In liv- Most donated livers come from deceased ing donor transplantation, a segment of the donors—donors who have recently died. donor’s healthy liver is surgically removed Adults usually receive the entire liver from a and transplanted into the recipient. Because deceased donor, although a segment of the a healthy liver can regenerate, the donor’s liver can be transplanted when the donor liver soon grows back to normal size after liver is too large. Because few donor liv- the surgery, while the segment of the liver ers come from children, pediatric recipients that was transplanted into the recipient also more often receive a portion of a liver from grows to normal size. an adult donor. Occasionally, an adult liver is split into two portions and given to two dif- The entire left lobe or a portion of the left ferent recipients. For example, the smaller lobe of the liver from a living adult donor left lobe may be given to a child and the is usually sufficient for transplantation in a larger right lobe given to an adult. child. For adult recipients, the larger right lobe of the liver may be needed. However, the removal of the right lobe of the liver from a living donor is a challenging and Right lobe complex surgery with significant risks to the Left lobe donor, including death. According to the OPTN, about 16,000 people in the United States were on the waiting list for a liver transplant in 2008, and 6,318 liver transplants were performed.1 Because not enough donated livers are available, many people on the waiting list must wait a long time to receive a liver, and up to one out of 10 die while on the waiting list. More donors Liver are needed to meet the demand. Informa- tion about is available from the UNOS at www.unos.org and from the HRSA at www.organdonor.gov.

The liver

1The and Transplantation Network website. http://optn.transplant.hrsa.gov. Accessed October 28, 2009. 5 Liver Transplantation How are liver donors What happens during liver and potential recipients transplant surgery? matched? When a suitable liver from a deceased donor Livers for transplantation are identified and is matched to a person who is ready to allocated through policies developed by the receive it, the surgery is scheduled as quickly OPTN. The UNOS maintains a central- as possible. The recipient completes presur- ized computer network that links all organ gical testing and is prepared for surgery while procurement organizations and transplant the donor liver is obtained, transported to centers in the United States. Livers are allo- the hospital, and carefully checked to ensure cated to specific recipients based on the sta- it is suitable for transplantation. tus 1 and MELD and PELD scoring systems, Liver transplant surgery is complex and can which give priority to people with the most take up to 12 hours. The patient receiving urgent need for a new liver. Donors and the liver requires general anesthesia given recipients are matched on the basis of having through a breathing tube inserted into the compatible blood types and ideally should be windpipe, intravenous lines to provide medi- similar in size. cine and fluids, and a catheter to drain urine. When a donor liver becomes available, An incision is made in the upper abdomen, information about the donor is entered into and the surgical team detaches the diseased the UNOS computer system. The computer or injured liver from blood vessels and the creates a ranked list of potential recipients common , clamps the vessels and with compatible and size for the duct, and removes the liver. The team then donor liver. The UNOS then offers the liver attaches the recipient’s blood vessels and to the transplant team at the center with the common bile duct to those in the donor patient at the top of the list. The transplant liver. The donor liver is typically placed team has the right to decline the liver for that in the same location where the diseased patient. The team might be forced to decline or injured liver was. Tubes are sometimes the donated liver if, for example, placed around the transplanted liver to allow • � the patient’s condition has improved blood and fluids to drain out of the abdo- men. A tube may be used to temporarily • � the patient’s condition has deteriorated drain bile from the new liver into an exter- • � the transplant team’s assessment is that nal pouch so the bile can be measured to the donor liver is unlikely to function determine whether the liver is producing bile properly in the recipient as it should. In cases where the recipient’s common bile duct cannot be connected to If a donor liver is declined, the UNOS imme- the donor’s bile duct, the donor bile duct is diately offers the donated liver to the next drained into a loop of small intestine. patient on the list.

6 � Liver Transplantation After surgery, the patient goes to an anes- In addition, liver diseases can recur in trans- thesia recovery area and then to an intensive planted livers. The transplanted liver can care unit. After the patient is stabilized, be damaged if, for example, a person who the breathing tube used for anesthesia is had cirrhosis caused by long-term alcohol removed and the patient moves out of inten- abuse resumes drinking after the transplant. sive care and into a regular hospital room. Recurrence of certain liver diseases such as Patients usually stay in the hospital from 1 to can also damage the transplanted 2 weeks after a liver transplant. liver. Recurrence of hepatitis B in the trans- planted liver can now be prevented. Finally, Living donor transplants involve two surger- autoimmune diseases, such as autoimmune ies performed in the same hospital. In one hepatitis, primary biliary cirrhosis, and pri- operating room, a surgical team removes mary sclerosing cholangitis, may also recur. the transplant recipient’s diseased or injured liver. In another operating room, another If a person’s transplanted liver fails as a surgical team removes a segment of the result of rejection or recurrent disease, the donor’s healthy liver. Then the segment of doctors on the transplant team must decide donor liver is transplanted into the recipi- whether another transplant is possible. ent. Otherwise, the surgery and recovery for the recipient is similar to that for a recipient What is liver transplant of a liver from a deceased donor. The liv- ing donor typically remains hospitalized for rejection and how is it about 1 week after surgery. treated? Rejection occurs when a person’s immune What are the complications system recognizes the transplanted liver as of liver transplantation? “foreign” and tries to destroy it. Rejection commonly occurs a week or two after a trans- Possible complications of liver transplant plant, although rejection can occur at any surgery include time that immunosuppressive medications • � bleeding fail to control the patient’s immune reaction. Rejection does not always cause noticeable • � damage to the bile ducts symptoms. Elevated liver enzyme levels in • � blood clots in the liver’s blood vessels the blood may be the first sign that rejection is occurring. Other signs and symptoms of • � infection rejection may include fatigue, loss of appe- • � rejection of the new liver by the body’s tite, nausea, abdominal tenderness or pain, fever, jaundice, dark-colored urine, or light- colored stools. • � side effects from the immunosuppres- sive medications liver transplant recipi- ents must take to prevent rejection

7 � Liver Transplantation A liver is usually needed to verify that some medications may be eliminated or rejection is occurring in the transplanted doses may be lowered to minimize side liver and exclude other causes of symptoms effects. One year after transplantation, or abnormal liver enzyme levels. A biopsy many patients require only , involves using a needle to remove a small cyclosporine, or sirolimus. piece of liver tissue to be examined with a Immunosuppressive medications can have microscope. significant side effects. By suppressing the Immunosuppressive medications are used immune system, the medications can make to decrease the activity of the recipient’s patients more susceptible to infections. immune response to prevent and treat rejec- Other possible side effects include tion. Transplant recipients must take immu- • � weight gain—prednisone nosuppressive medications for the rest of their life to prevent rejection. • � diabetes—tacrolimus, cyclosporine Immunosuppressive medications commonly • � high blood pressure—prednisone, tac- given after a transplant include rolimus, cyclosporine, sirolimus • � intravenous methylprednisolone (Depo- • � high blood cholesterol or triglycerides— Medrol, Solu-Medrol), which is given cyclosporine, sirolimus during and immediately after surgery, • � osteoporosis—prednisone and prednisone (Deltasone, Sterapred), once oral medications can be given • � kidney damage—tacrolimus, cyclosporine, sirolimus � • � tacrolimus (Prograf) or cyclosporine (Neoral, Sandimmune) � Long-term use of immunosuppressive medications can also increase a person’s risk • � sirolimus (Rapamune), which cannot of developing cancers of the skin and other be used for several months after a liver sites. Yearly monitoring is required to detect transplant because it can cause blood any cancers at an early, treatable stage. clots in the major artery providing blood to the transplanted liver and prevents A number of medications, as well as grape- the surgical wounds from healing; how- fruit and grapefruit juice, can increase ever, sirolimus is safe once the artery or decrease the levels of tacrolimus, and wounds have completely healed cyclosporine, and sirolimus in the body. To prevent complications caused by the levels • � mycophenolate mofetil (CellCept), of these immunosuppressive medications (Myfortic), and becoming either too high or too low, people azathioprine (Azasan, Imuran), which taking these medications should avoid grape- may be given along with cyclosporine or fruit and discuss any new medications— tacrolimus prescribed or over-the-counter—with their In general, a transplant recipient needs transplant team. to take more medications during the first several months after a transplant, and later

8 � Liver Transplantation What is the outlook for Points to Remember people who have a liver • � Liver transplantation is surgery to transplant? remove a diseased or injured liver and replace it with a healthy whole liver or a Most liver transplants are successful. About segment of a liver from another person, 80 to 85 percent of transplanted livers are called a donor. functioning after 1 year.2 People who have a liver transplant are usually able to return to • � People with either acute or chronic liver normal activities after recovering for several failure may need a liver transplant to months. survive. Liver transplant recipients receive intensive • � In adults, chronic liver failure due to cir- medical follow-up during the first year after a rhosis caused by hepatitis C is the most transplant. They have regular blood tests to common reason for liver transplantation check whether the liver is being damaged by in the United States. The second most rejection, infections, or problems with blood common reason is cirrhosis caused by vessels or bile ducts. long-term alcohol abuse. � To help achieve a good outcome after a liver • In children, biliary atresia is the most transplant, recipients need to common cause of liver failure and the need for a liver transplant. • � follow instructions for taking • � The process for getting a liver trans- medications plant begins with referral to a transplant • � keep all medical appointments center, where a transplant team care- • � avoid people who are ill and let their fully evaluates candidates to determine doctor know when they are ill whether they are suitable candidates for transplantation. The transplant center’s • � learn to recognize the signs of rejection liver transplant selection committee and infection and report them promptly decides whether to register a candi- to their doctor date on the national waiting list for a • � maintain a healthy lifestyle by making transplant. healthy food choices, exercising, not • � The national waiting list is maintained smoking, and not drinking alcohol by the United Network for Organ Shar- ing (UNOS). The UNOS administers the U.S. Organ Procurement and Trans- plantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services. • � People on the waiting list are assigned 22008 annual report of the U.S. Organ Procurement a score that indicates how urgently they and Transplantation Network and the Scientific need a transplant. The two scoring Registry of Transplant Recipients: transplant systems are the Model for End-stage data 1997–2007. Health Resources and Services Administration, Healthcare Systems Bureau, Division Liver Disease (MELD) scoring system, of Transplantation website. www.ustransplant.org/ used for people age 12 and older, and annual_reports/current. Accessed October 28, 2009. 9 � Liver Transplantation the Pediatric End-stage Liver Disease Hope through Research (PELD) scoring system, used for chil- The National Institute of Diabetes and dren younger than 12. A higher score Digestive and Kidney Diseases (NIDDK), indicates a more urgent need for a liver through its Liver Disease Research Branch, transplant. focuses and accelerates research on liver • � Critically ill patients with acute liver disease within the Institute and helps coor- failure who are likely to die within a dinate and stimulate liver-related research week are categorized as status 1 patients across the National Institutes of Health and and are given highest priority for liver within other federal agencies. The NIDDK transplantation. aims to improve long-term success and organ • � Most livers for transplantation come availability for liver transplantation as a from deceased donors. A small number treatment of acute and chronic liver failure of transplants involve living donors, who and to provide a means to reliably diag- donate part of their liver, usually to a nose, manage, treat, and prevent its major family member. complications. • � Liver transplant surgery is complex The NIDDK supports and conducts a wide and can take up to 12 hours. Patients variety of research related to liver diseases, usually stay in the hospital from 1 to liver failure, and liver transplantation. 2 weeks after a liver transplant. Examples of studies funded by the NIDDK include those investigating adult-to-adult • � Complications after liver transplant living donor liver transplantation, ways to surgery may include bleeding, bile leaks, prevent the recurrence of hepatitis C after blood clots in the liver’s blood vessels, liver transplantation, and acute liver failure infection, rejection of the new liver, and in children. side effects from immunosuppressive medications. Participants in clinical trials can play a more active role in their own health care, gain � • Liver transplant recipients must take access to new research treatments before immunosuppressive medications for the they are widely available, and help others rest of their life. by contributing to medical research. For • � Most liver transplants are successful. information about current studies, visit People who have a liver transplant are www.ClinicalTrials.gov. usually able to return to normal activi- ties after recovering for several months.

10 Liver Transplantation For More Information Acknowledgments American Association for the Study of Publications produced by the Clearinghouse Liver Diseases are carefully reviewed by both NIDDK sci- 1001 North Fairfax, Suite 400 entists and outside experts. This publication Alexandria, VA 22314 was reviewed by Ann Harper, United Net- Phone: 703–299–9766 work for Organ Sharing; Michael R. Lucey, Fax: 703–299–9622 M.D., University of Wisconsin–Madison; and Email: [email protected] John M. Vierling, M.D., Baylor College of Internet: www.aasld.org Medicine, Houston. American Liver Foundation 75 Maiden Lane, Suite 603 You may also find additional information about this New York, NY 10038–4810 topic by visiting MedlinePlus at www.medlineplus.gov. Phone: 1–800–GO–LIVER This publication may contain information about (1–800–465–4837) or 212–668–1000 medications. When prepared, this publication Fax: 212–483–8179 included the most current information available. For updates or for questions about any medications, Internet: www.liverfoundation.org contact the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–888–463–6332) or Hepatitis Foundation International visit www.fda.gov. Consult your doctor for more 504 Blick Drive information. Silver Spring, MD 20904 Phone: 1–800–891–0707 or 301–622–4200 Fax: 301–622–4702 The U.S. Government does not endorse or favor any Email: [email protected] specific commercial product or company. Trade, Internet: www.hepfi.org proprietary, or company names appearing in this document are used only because they are considered Organ Procurement and Transplantation necessary in the context of the information provided. Network If a product is not mentioned, the omission does not mean or imply that the product is unsatisfactory. Internet: http://optn.transplant.hrsa.gov United Network for Organ Sharing P.O. Box 2484 Richmond, VA 23218 Phone: 1–888–894–6361 or 804–782–4800 Internet: www.unos.org

11 Liver Transplantation National Digestive Diseases Information Clearinghouse 2 Information Way Bethesda, MD 20892–3570 Phone: 1–800–891–5389 TTY: 1–866–569–1162 Fax: 703–738–4929 Email: [email protected] Internet: www.digestive.niddk.nih.gov The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health of the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.

This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired. This publication is available at www.digestive.niddk.nih.gov.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health

NIH Publication No. 10–4637 June 2010