Report From Dallas AASLD 2001 (Transplantation)

Liver Transplantation

http://209.41.169.29/200112/page1.cfm
 

The most public health oriented message among the liver transplant presentations was the negative impact continued cigarette smoking has on develop-ment of cardiovascular disease (CVD) morbidity among post-transplant HCV+ patients. Dr. Pungpapong and colleagues from Albert Einstein in Philadelphia followed a cohort of 288 transplanted HCV+ patients who received cadaveric liver trans-plants in that center from May 1995-April 2001. Study endpoints included both graft rejection, CVD morbidity, sustained immunosuppression, and control of HCV disease management post-transplant.

The take-home message from this presentation was that EVER or FORMER smokers experienced a 2.5 times greater risk of developing an arterial complica-tion within the 6-month post-transplant period than non-smokers. The two primary arterial problems were hepatic arterial thrombosis and hepatic arterial stenosis or HAT and HAS. These are blockages in the hepatic artery in the liver. Cigarette smoking’s impact on development of ventricular problems was not statistically significant. Further, this group reviewed how long prior to receipt of liver transplant a patient would have to stop smoking to receive any potential benefit in NOT developing CVD problems post-transplant.

The group reported that patients would, ideally, have to stop smoking a minimum of 2 years prior to transplantation to reduce this risk by 50%. The study group would have to enroll 8 non-smokers with that history to prevent one arterial complication. Your reporter asked two questions of this investigative team: (1) were they able to tease out if there were less arterial problems among occasional, as in < 1/2 pack daily smokers than other smokers - No, they are currently assessing this; and (2), given that a trend for worse arterial problems seemed to be present in women transplant patients, what role, if any, does current or historical use of hormonal— particularly oral contraceptive-play in increasing arterial problems.

The investigator indicated that most of these women were of menopausal age and that they had neither asked nor answered that question nor assessed if use of hormonal replacement therapy (HRT) may be decrease incidence of arterial prob-lems in this population.

Costs and Other issues in HCV treatment for pre and post-liver transplant patients

Two additional papers in this afternoon series looked at treatment for hepatitis C pre- and post-liver transplant, and for patients receiving living donor liver transplants. It is well known that HCV+ transplant patients have more problems with graft (liver or other organ) rejection post-transplant than non-HCV+ patients. Rates of infection may also be higher in the HCV+ group, and in most patients HCV disease returns within one year post-transplant. The big debate is whether and when to treat transplant patients -pre or post transplant, and assessing the very real cost constraints that treatment may present in this population.

The first paper, presented by Dr. Saab for the UCLA liver transplant and hepatology team, compared the cost-efficacy of standard IFN+ ribavirin (non-pegylated IFN) treatment in post-liver transplant patients to that of no treatment using a decision analysis model initially developed for post-lumpectomy and mastectomy breast cancer patients.

This model looked at cost savings potentially realized by preventing cirrhosis in a hypothetical HCV+ post-transplant group. The key finding from this study is that while antiviral therapy assumed to cost $13,881 for a course of treatment prevented 31 new cases of cirrhosis, 4 deaths, and offered a substantial cost-effectiveness ratio of greater than $100,000, the model is most robust if: a sustained viral response is at least 40% and the antiviral treatment costs were less than 38% of the baseline treatment costs or about $4300. This may not be a workable model in sicker or older patients with more co-morbidities post-transplant, and will have to be re-evaluated for the new pegylated IFN products. This research group is currently re-analyzing this model with use of pegylated IFN + ribavirin and with non-genotype 1 patients.

A second paper looked at the impact of HCV treatment in pre-transplant patients receiving living donor liver transplants. While living donor liver procedures remain controversial given higher expected mortality and morbidity among the donors, the procedure provides an important life-giving resource to recipients. This procedure may be the only mechanism for receiving a liver transplant among metha-done or other drug treatment patients who are often denied access to cadaveric livers. This paper was presented by Dr. Trotter and colleagues from the University of Colorado in Denver, CO. Since live donor liver transplantation (LDLT) is a scheduled medical procedure, this Colorado group set up a small study among 24 patients receiving this procedures at their center in the period of 8/97-3/01. Twelve (12) of the patients received pre-transplant anti-viral therapy, six (6) with standard of care combination therapy (non-pegylated IFN) with ribavirin, and another six patients received a modified low accelerating dose (LADR) of IFN and ribavirin with gradually accelerating levels of ribavirin. The regimen was well tolerated in all groups, 50% (3 patients) were non-responders pre and post-transplant and 3 pa-tients were sustained viral responders pre and post-transplant (last procedure completed 3/01). Four of these six patients were genotype 1, and one genotype 1 patient was a sustained viral responder both pre and post-transplant. Despite the small sample size, this research team felt that pre-treatment with standard anti-viral therapies might reduce post-transplant re-infection with HCV and post-transplant graft rejection and death from recurrent HCV. An additional study is underway with the new pegylated IFN product and will be submitted to DDW 2002.

Other Transplant Issues

A great deal of debate emerged within many of these sessions about the morbidity issues for living liver donors. In brief some interesting findings included: need for better and more aggressive cardio-vascular disease (CVD) screening among living liver donors because of the development of CVD particularly among female and older donors; the role hormonal contraceptive use may play in increasing cardiovascular disease morbidity for female living liver donors; the negative impact advancing age of the donor livers (both cadaveric and living donors) may have on transplant recipient response (livers from donors over age 60 seem to result in more graft rejection and higher infections); and the interaction of recipient gender and HCV on graft rejection (female livers to male donors resulting in the highest percentage of rejection, which may be accelerated or mediated by female sex hormones). In many transplant centers it is often the female member of families who elect to donate a portion of their liver to male partners, spouses, or male children, thus the acute interest in this topic. Since most of these sample sizes were quite small (under 25 cases), multi-center studies with pooled data would be valuable in further analysis. Expect more on this topic from our reports from DDW in May 2002.
 

The Liver Transplant: Evaluation, Waiting, Surgery, and Returning Home
 

Doctors may recommend a liver transplant to treat liver failure. Failure may be due to  disease or injury. The most common categories of disease are cirrhosis (liver scarring) from hepatitis or alcohol, cholestatic disorders, metabolic diseases, and certain cancers.

It is also possible to have liver failure due to viral infections, toxins, or medication reactions. The person who needs the transplant is evaluated by a liver transplant team and if they are found to be suitable, his or her name is placed on the waitlist. When a donated liver becomes available, it is surgically removed from the donor and transplanted into the patient.

Because the liver has the ability to regenerate, in some cases a portion of the liver from a living donor can be removed and transplanted within a recipient with liver failure. Both the donor and recipient will regenerate a liver back to normal size. Use of this type of transplantation is increasing rapidly.

Among 7,502 patients who underwent liver transplants in 1997 and 1998, about 80% survived for at least three years afterwards.


Step 1: Evaluating candidates for liver transplantation
A team of specially trained staff evaluates the patient to establish whether he or she would be a good candidate for a liver transplant. The staff includes people with special skills in a range of areas. The people who may be on the team include:

• Hepatologist (medical liver specialists)
• Transplant surgeons
• Social workers, psychologists, and/or psychiatrists
• Nurses
• Transplant coordinators

A liver transplant is only offered to people who have irreversible, chronic liver failure. Other medical or surgical treatments for liver problems have usually been tried before consideration of liver transplant. The liver failure may have been caused by problems such as:

• Cirrhosis, a chronic disease of the liver due to alcohol or other causes
• Viral hepatitis (B, C, D)
• Sudden liver failure
• Biliary atresia, an obstruction of the bile ducts caused by their failure to develop normally before birth
• Certain metabolic disorders such as Wilson disease, an inherited disorder in which the body has too much copper
• Drug-induced liver injury
• Noncancerous tumors of the liver and certain cancerous tumors of the liver or bile duct
• Problems with the major blood vessels that supply the liver

Successful liver transplants have been conducted on newborn infants, children and adults including people past the age of 70.

The evaluating team considers many factors to decide whether a person should be placed on the wait list for transplantation. The person's general health and suitability for major surgery are taken into account. Risk factors are considered carefully and may result in a recommendation against transplant surgery.

A liver transplant would not be performed for people with certain conditions. These include:

• Most cancers, unless successfully treated at least five years previously
• Infections that cannot be completely treated or cured, such as tuberculosis
• Severe lung or kidney problems that would make the operation too risky

It is a normal reaction of the body to reject the donated organ. Anti-rejection drugs are prescribed to prevent this rejection. The candidate must be willing to take anti-rejection medicines indefinitely to keep the body from rejecting the donor liver. The person will also need lifelong follow-up by health care professionals.

Step 2: Waiting

If a person is a suitable candidate for a liver transplant, their name is put on a waiting list for an organ. Unfortunately, there are many more people on the wait list than there are organs available each year.

There are currently more than 18,000 people in the U.S. waiting for a donor liver. Waiting time may extend several years.

People waiting for donor livers are grouped by the severity of illness and other medical factors such as blood type. Within any given group, livers are allocated based on the length of time a person has been on the wait list.

A new system, the Model for End-stage Liver Disease (MELD) has recently replaced the previous 3 medical severity stages for liver transplant candidates with chronic liver diseases with a scale that goes from 6 to 40. The MELD system is based on three simple to measure laboratory tests, and the MELD score is predictive of death within 3 months (the higher the score, the higher the risk of death).

Candidates with sudden, acute liver failure (status 1) are still allocated organs ahead of all other waiting patients. A system similar to MELD has been developed for children (PELD), which utilizes the same three laboratory tests in addition to a fourth blood test and a measure of growth failure.

For more specifics on current allocation policies, please go to the website of the The Organ Procurement and Transplantation Network.

Step 3: The Transplant Surgery

If the donor is living, they will receive general anesthesia and the transplant of the liver into the recipient will occur immediately after the removal of the organ from the donor. Therefore, the patient receiving the transplant is prepared for surgery within the same time frame as the donor. They, too, will receive general anesthesia.

When a cadaveric liver becomes available, time is critical. The liver must be transplanted into the patient receiving the organ within 12 to 18 hours. A team of surgeons and anesthesiologists performs an operation to remove the liver from the donor. Additional surgical teams may be present to remove other organs.

After the liver is removed from the donor, it is preserved and packed for transport. Although the donor is brain dead, this procedure is treated like any other operation using standard surgical practices and sterile techniques.

Once the operation is complete and the incisions are closed, the donor's body is prepared for funeral or cremation. Organ procurement surgery respects the body and an open casket funeral is possible if desired.

In the meantime, a recipient is located and prepared for surgery. Preparation involves administration of general anesthesia. The transplant of the liver begins with an incision in the upper part of the abdomen. First, the diseased liver is removed. When the new liver is placed within the recipient, the blood vessels from the donor liver must be connected to the recipient's blood vessels. Next, the blood flow is restored. The bile duct, which carries bile made in the liver to the intestine, is also connected. After the transplant is complete, the incision is closed. The patient will begin recovery in the intensive care unit (ICU).

Step 4: After Transplant Surgery

Following liver transplant surgery, the patient may remain on an artificial breathing machine for the first 24 to 48 hours of recovery. Depending on progress, some patients are moved out of the ICU in a few days. Generally, he or she will also begin eating within the week following surgery. Total hospital stay can be a little as 1 week, and is typically a couple of weeks.

Because the organ will be identified as foreign by the recipient's immune system, rejection of the new liver is always a possibility. Powerful drugs called immunosuppressants are given starting at the time of liver transplant surgery to try to prevent rejection. Within the first few weeks following transplantation, blood tests are done to confirm that correct dosage of medication is being dispensed.

Prior to discharge, the transplant team reviews information with the patient, gives instruction for follow-up care and medications, and answers the patient's questions. A prescribed rehabilitation program will continue at home including exercise, nutrition, and the continuation of immunosuppression and other medications. The signs of rejection are also discussed with the patient and family.

Living donors do not have to take any specific medications or maintain a special diet as a result of liver donation.

Step 5: Returning home

At-home rehabilitation for liver transplantation is a gradual process and depends on the individual. The transplant team will give specific instructions. In general, walking is recommended to restore strength and prevent lung complications, but heavy lifting should be avoided for four to six weeks following transplant surgery. Other activities, such as driving may usually begin when the incision is free of pain. Sexual activity can resume when one is comfortable. A desire to become pregnant should be discussed ahead of time with the transplant team to determine if and when this is recommended.

Follow-up visits are required for check-ups. These begin soon after returning home. Initially, outpatient visits may occur weekly or even more often, and as time progresses the frequency of follow-up visits usually decreases.

Possible post-operative complications may arise following liver transplant surgery. They include:

• Bile duct problems
• Major bleeding
• Problems with blood vessels

Bile duct problems - Complications can arise with the connection between the donor and recipient bile duct or between the donor bile duct and intestine. If it does not heal properly, bile may leak out. Scar tissue can also block the bile duct causing bile the inability to flow.

Major bleeding - It is common for a liver transplant patient to experience bleeding after surgery. The new liver needs time to make blood-clotting proteins. Patients usually need blood transfusions, and an additional operation may be required within the first 24 to 48 hours after the transplant to resolve the problem.

Problems with blood vessels - Complications can arise with blood vessel connections between the donor liver and the recipient's blood vessels. A more serious complication is a clot in an artery or vein attached to the liver. If a clot occurs, the liver may fail.

Other problems include the long-term risks of immunosupression. These include complications related to too much or too little immunosuppression:

• Rejection
• Cancer
• Infection

Rejection - It is fairly common for a transplant patient to experience rejection episodes. The body identifies the new organ as foreign and may try to reject it. The immunosuppressive medications prevent rejection in 50 to 75% of cases. Changes may be made in the medications including an increase in dosage or the use of additional drugs to stop the rejection. Some episodes can cause permanent damage to the new liver. This may reduce longevity of the organ.

Cancer - Studies show that an estimated 6% to 8% of transplant patients will develop cancer over their lifetime with the transplant. This risk is higher than in the general population. Skin cancer is the most common, and is typically treated successfully. Some cancers result from the effects of the immunosuppressive medications and others are common cancers that occur at a higher rate in immunosuppressed individuals.

Infection - The immunosuppressant medications increase the risk of less serious and common infections such as urinary tract infection. In addition, they are associated with more serious infections like pneumonia. Finally, uncommon infections that do not affect non-immunosuppressed persons can occur.

Living donors are generally followed by the transplant team for a considerable period of time until recovery is complete.

More information is available from

American Liver Foundation
75 Maiden Lane, Suite 603
New York, NY 10038
Phone: 1-800-GO-LIVER (465-4837)
Email: info@liverfoundation.org
Internet: www.liverfoundation.org

Hepatitis Foundation International (HFI)
504 Blick Drive
Silver Spring, MD 20904-2901
Phone: 1-800-891-0707 or (301) 622-4200
Fax: (301) 622-4702
Email: hepfi@hepfi.org
Internet: www.hepfi.org

United Network for Organ Sharing
1100 Boulders Parkway
Suite 500
P.O. Box 13770
Richmond, VA 23225-8770
Phone: 1-888-894-6361 or (804) 330-8500
Internet: www.unos.org

05/14/03

Source
National Institutes of Health

Transplantation of hepatitis C­positive livers in hepatitis C­positive patients is equivalent to transplanting hepatitis C­negative livers

Authors: Carlos E. Marroquin and a team of researchers from the Dept of Surgery, Division of Transplant and Hepatobiliary Surgery, Georgetown University Medical Center, Washington DC; and the United Network for Organ Sharing, Richmond, Va.

Abstract

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus­positive (HCV+) donor livers for HCV+ recipients. This study reviews the clinical outcome of a large series of HCV+ recipients of HCV+ liver allografts and compares their course with that of HCV+ recipients of HCV-negative (HCV­) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV+ transplant recipients were analyzed. Two groups were identified: a group of HCV+ recipients of HCV+ donor livers (n = 96), and a group of HCV+ recipients of HCV­ donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV+ allograft (8.3% v 3.1%; P = .01). Patient survival showed a significant difference for the HCV+ group compared with the HCV­ group (90% v 77%; P = .01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV+ group and only 1.3% in the HCV­ group (P = .04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV+ recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV+ donor livers for transplantation in HCV+ recipients safely and effectively expands the organ donor pool. (Liver Transpl September 2001;7:762-768.)

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Approximately 4 million Americans are infected with hepatitis C virus (HCV). During their lifetime, an estimated 20% of HCV-infected individuals will develop cirrhosis and subsequently develop complications of cirrhosis, including ascites, encephalopathy, and/or variceal bleeding. A significant number of these individuals will eventually die of disease-related complications. For some, if not most, of these individuals, liver transplantation offers the only truly effective alternative. Unfortunately, the demand for liver transplants far exceeds the organ supply. Given the prevalence of HCV infection in the population, approximately 2% to 5% of potential organ donors are also infected with HCV. Because of concerns about viral transmission and allograft dysfunction, these organs were not generally considered for use in transplantation, potentially wasting viable organs.

Given the significant disparity between organ supply and demand for transplantation, it becomes critical to develop new technologies to support patients with end-stage liver disease. In the absence of new means of support, it is crucial to consider ways to expand the viable organ supply. Some groups have turned toward using marginal donors for liver transplantation, with reasonable success. Specifically, Fishbein et al found that livers with severe microvesicular steatosis can be used for transplantation with 1-year patient and graft survival rates of 80% and 72%, respectively. Furthermore, Mor et al found that extending their limits to accept older donors and those with moderately abnormal liver function test results or prolonged ischemic times did not affect graft survival.

However, even the incorporation of marginal organs into the donor pool leaves a huge deficit in the necessary supply. Therefore, other groups have used hepatic allografts from HCV+ donors for transplantation into HCV+ recipients. One concern regarding the use of HCV+ donor livers for transplantation is that one might introduce a more virulent strain of virus than the patient already harbors. However, there is little evidence to support this concern. Vargas et al showed that transplant recipients in whom the predominant HCV genotype belonged to the donor were less likely to develop recurrent hepatitis than those patients who retained their original strain. Because these studies were from single Institutions, we sought to confirm these findings on a larger national scale using the UNOS SR.

One alternative is to transplant HCV-positive (HCV+) donor livers into HCV+ patients with end-stage liver disease. Some groups have found this to be a safe and effective practice. Vargas et al3 found no significant difference in 1- and 5-year survival of patients who received an HCV+ donor liver compared with those who received an HCV-negative (HCV­) donor liver. Furthermore, there was no difference in graft failure rates between the 2 groups. Moreover, when they examined the risk for infection with donor viral strain, they found that patients in whom the predominant HCV genotype after transplantation was that of the donor were significantly less likely to develop recurrent hepatitis than those patients who retained their own strain. Similarly, Testa et al found no difference in patient and graft survival when they compared their institution's experience with recipients of an HCV+ donor liver versus recipients of an HCV­ donor liver.

Previous reports examining the use of HCV+ allografts have been hindered by small study populations. The purpose of this study is to compare clinical outcomes of a large series of HCV+ recipients of liver allografts from either HCV+ or HCV­ donors using the United Network for Organ Sharing (UNOS) Scientific Registry (SR). UNOS coordinates the 272 transplant centers and the medical, scientific, and technological resources needed to facilitate organ transplantation nationally. The UNOS SR provided the large numbers necessary to overcome the small sample size hindering other studies. The goal is to determine the effect of hepatitis C serology of the donor on patient and graft survival. Other factors that were compared included recipient and donor characteristics, effect of coexisting diseases, liver function test, immunosuppression, UNOS status at transplantation, and causes of graft failure. Finally, the most important goal is to establish whether one could safely expand the donor pool by using livers from HCV+ donors for patients with end-stage liver disease secondary to hepatitis C.

Only 10% (n = 10) of the HCV+ donor group died during the study period versus 23% (n = 633) of the HCV­ donor group. Patient survival rates for the 2 groups at 6, 12, 18, and 24 months were 95%, 90%, 90%, and 90% versus 85%, 82%, 79%, and 77%, respectively. Median follow-ups were 1,023 days for the HCV+ donor group and 1,123 days for the HCV­ donor group. When UNOS status at time of transplantation was reviewed, the comparison of waiting list status was significantly different (Table 5).

A greater percent of status 3 patients received an HCV- graft than status 1 patients (Table 5). This may provide a better explanation for the improved survival. Because these patients received their grafts before they were hospitalized or ICU bound, they had the physiological reserve necessary to translate into an improved outcome.

To safely optimize the use of all available livers for transplantation, the practice of performing biopsies before procurement should be adopted when a question of organ viability arises. If significant steatosis or fibrosis is noted, that allograft should be abandoned. Despite the observed safety of using HCV+ donor livers for transplantation, there will always be concern with the potential risk for greater infectivity and pathogenicity of concurrent infection with 2 different viral strains and a greater rate of viral recurrence. To ameliorate or at least lessen the risk for graft failure secondary to recurrent hepatitis, one strategy may involve posttransplantation antiviral therapy as an adjunct to using HCV+ donor organs. Johnson et al9 found that antiviral therapy with interferon-alfa significantly improved the clinical course of patients who developed recurrent HCV hepatitis after liver transplantation. Further support for adjuvant therapy is provided by Boillot et al, who found that early and prolonged interferon-alfa therapy improved graft survival. Therefore, similar benefits may be derived from treatment of HCV+ patients who receive an HCV+ donor organ with interferon-alfa.

Although this study only bridges a 2-year period, it is the first large-scale analysis indicating that donor hepatitis C status does not negatively impact on either graft or patient survival after liver transplantation of an HCV+ patient. Greater long-term follow-up is needed to be certain of the safety and efficacy of this practice. However, given the limited number of organs, it is necessary to continue to develop new strategies to optimize the utilization of all available allografts.

WAITING FOR THE TRANSPLANT
 

Many have called the waiting period the most difficult part of the transplant process. This is due in part to the physical problems and progressive weakness associated with end-stage organ disease, the personal and family stresses of dealing with major illness, but mainly due to the uncertainty of not knowing when a donor organ and the call for transplant will come.
It is not unusual to feel discouraged, frustrated, depressed, and yes, even angry as the unpredictable wait may go on for months or even years. It is important to stay focused on attaining the goal of receiving a transplant and doing everything you can to be prepared when the call finally comes.
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How will they find me when an organ becomes available?

Once your name has been placed on the national transplant waiting list, the transplant coordinator will give you and your family specific instructions on how the communication process works at your transplant center.
When an organ becomes available, things will happen very quickly. Since most patients are not hospitalized when the donor organ becomes available, it is imperative that the coordinator is able to reach you by phone within minutes of accepting the organ offer. Because this can happen anytime of the day or night, the team will need to be able to reach you at home, work, school, on vacation or while traveling.

Some tips regarding easy communication:
Make sure that your coordinator has an accurate list of phone numbers where you can be located. Include day and night time numbers such as work/school and home, a next-door neighbor, family or friends that may be able to locate you in a timely manner.
Obtain a pager (beeper) and/or cell phone. Before you purchase one of these devices, discuss the issue with the transplant coordinator. He/she will give you more detailed instructions and a recommendation for which is preferable and more practical for use in your situation. The coordinator may be able to put you in touch with an organization that provides pagers free of charge to patients waiting for transplantation. Remember these devices only work if you keep the batteries charged and carry them with you at all times. You must notify your coordinator immediately if the phone number for the paging devices is changed or if the device is not working. Remember there are certain geographical locations in which pagers and cell phones may not work (tunnels, canyons, behind a mountain, in a deep basement, in certain office or plant areas).
Do not give out your pager number indiscriminately. The pager is intended to alert you to call the transplant office. Unnecessary use will only confuse you and result in unneeded calls to the transplant office.
An answering machine will come in handy for non-urgent messages and communication with the transplant office.
Discuss any plans for vacation, business travel, weekend or night visits with your coordinator. If your travel plans take you a significant distance from home and the transplant center or if transportation might be delayed (such as camping in a remote area, on a boat, or a city with lack of timely airline connections) you might want to reconsider your plans or risk the possibility of missing out on an organ offer.
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Be Prepared

Along with having a good system for timely communication with your transplant center, there are many other things you should do to be prepared for the time when the call comes telling you that an organ is available. Once you get the call, things will start to move very quickly. This will be a hectic, exciting and even scary time for you and your family. So plan ahead, just like an expectant mother who has her bag packed and ready to go to the hospital at a moment’s notice. Develop a plan with your family/friends and even co-workers. Make a checklist of what you will need to be done in order to get you on your way as quickly as possible. Don’t be afraid to assign specific responsibilities to family and friends.
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How will you get to the hospital?

Driving:
Decide in advance who will be driving you to the hospital and know how long it will take.
Do you and/or your driver know the route? Have the directions written down and have a map with the route marked.
Is the car prepared to go? Do you have gas? Where is the closest gas station and is it open all night? Be prepared for the seasons (are your winter tires on?).
Do you have an alternate plan if the car breaks down?
Make a dry run to the hospital.

Flying:
Not everyone lives close enough to the transplant center to drive; therefore, alternative arrangement via commercial or private plane might be necessary. You should discuss these arrangements in detail with your coordinator. He/she will assist you with investigating alternative travel arrangements.
Determine which airports are closest to you and the transplant center.
Make a list of all airlines that service your home airport and the airport nearest the transplant center. List phone numbers, departure and arrival times and the length of the flight. Direct flights are the best option.
Determine how long it will take you to get from home to the airport and who will drive you to the airport.
Determine how long will it take to get from the airport to the hospital and how will you get there.
Speak with a customer service representative from the airline in advance and ask what they might be able to do to expedite your travel when the transplant time comes. Since it is impossible to known in advance when the transplant will occur you can not book your flight in advance. Most airlines have been responsive to transplant medical emergencies and will be helpful in getting you on the first available flight, but you must politely explain the urgency when you call.
If commercial flights are infrequent from your local airport or logistically impractical, you may need to arrange for a private plane. This can be very expensive and may not be covered by insurance; therefore, it is only used as a last resort. You should discuss this with your transplant team prior to making any arrangements.
Remember all flights are dependent of weather conditions, so you should a backup plan.

Waiting in the hospital:
Some candidates, especially those waiting for heart or liver transplantation, may be too ill to wait at home. Patients with the most urgent medical category for these organs require hospitalization in the intensive care unit.
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What should I take to the hospital?

Both the patient and whoever will be accompanying the patient to the transplant center should have a suitcase prepared and ready to go. Keep it in a central place where it can be located easily (by your bedroom door, in the hall-closet, in the trunk of the car).

Patient:
Take only those items absolutely necessary. You will not need many items for the first few days and your family can bring additional items when needed.
Slippers and a robe
Glasses (remove contacts and leave at home if possible)
Insurance card
You may bring your wallet or purse but be prepared to give it to your family prior to surgery
Bring your current medications (in the labeled bottles not in a pill box or baggie)
Any personal items like pictures or religious items should be given to your family when you leave for surgery
Leave jewelry at home or give it to a family member as soon as possible.

Family:
Family housing arrangements near the hospital should be discussed with the social worker and/or transplant coordinator prior to transplant.
Pack sufficient clothing (comfortable clothes and shoes) and personal items for several days. Have other family members bring additional items, if needed.
Family members should remember to bring their own medications or medical supplies.
A “transplant survival kit”
Many families wish to wait at the hospital while the patient is in surgery. Since the entire waiting time may be 12 hours or longer the family should prepare a tote bag in advance with some essential, and comfort items.
A list of persons and phone numbers of those you and your family wish to call from the hospital
Change for a pay phone or a phone card
A note pad, pencil, pen to keep track of changing room locations, questions for the medical team, messages for other family members
Personal medications, an over-the-counter headache or pain reliever, a box of tissues, glasses, contact supplies, etc.
Gum, hard candy, snacks, bottle of water
Reading and/or hobby materials, like knitting, to help pass the time
Watch
Sweater, comfortable shoes or slippers, even a small pillow
Personal items such as small family pictures or religious items
Sufficient cash, credit card and/or checks

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Housing

Frequently patients do not live in close proximity to the transplant center. The social worker or transplant coordinator can assist you and your family in locating hotels or alternative housing that will meet your needs. Many transplant centers have their own facility specifically for transplant patients and their families.
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Other Suggestions:

Make prior arrangements as to who will watch the children, take care of pets, get the mail, watch the house, etc.
Develop a phone tree. Family and friends will be anxious to know when the time for transplant arrives. You will not have time to contact everyone, so give someone else the assignment of notifying others. Ask that only one or two of your immediate family members be designated as the primary communication contacts with your medical team. They can then relay updated information on the progress of the transplant to the rest of your family and friends. This will limit the number of calls to the transplant office and your immediate family can best decide on what information they want given to whom.
Good intentioned well wishers may want to send flowers or gifts to the hospital. Many transplant programs do not permit new transplant patients to have fresh plants and flowers in their room. Ask your coordinator in advance what the transplant and hospital policy is on such items. You may want to suggest some alternatives, such as donating blood to the local blood bank in the recipient’s name, making a donation to a transplant fund or organization, talking to their family and friends about organ donation and signing a donor card.
Although it may be a difficult subject to talk about, you should make sure that your personal affairs are in order.
Does your family know your wishes and know where to locate any important documents?
Do you have or have you updated any legal documents like a will, a medical and or financial power of attorney and are they updated?
Are your personal finances in order?
Are there friends or family you would like to call or see?
Are there spiritual or religious needs you would like to attend to?

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Staying in touch with your transplant team:
When should I call the doctor?

During this waiting time you will be scheduled for regular follow-up appointments with the transplant team. Maintaining your best possible health during the waiting period will help speed your post-transplant recovery. However, there are certain specific medical problems that are unique to patients with end-stage organ disease that require close monitoring.
Your doctors and coordinator will give you specific instructions on what to watch for and what to report to them.
If you are not sure if you should call the doctor/coordinator or not....CALL!
Obviously, your medical team would prefer to be called with questions or minor problems during office hours when your medical records are readily available, but you should never hesitate to call for urgent situations.

While preparing for transplant, it is important to take appropriate care of yourself. This includes lifestyle modifications, such as stopping smoking, decreasing sodium (salt) intake and exercising. Patients should also track any changes to your present condition and inform your transplant team of these changes.

It is also important to notify your transplant team anytime you change the number at which you can be reached. This includes if you move, if you are staying with a friend or relative for a few days or if you are traveling or going on vacation. Make sure you leave a number with the transplant team that will be checked regularly (every few hours). If you will be away for more than a few hours, it is best to have a cell phone number of pager number for the transplant team to reach you. You wouldn’t want to miss out on an opportunity to receive a transplant because the transplant team couldn’t reach you!

*from downloadable file on wordpad- "Waiting for Transplant" at
http://www.stadtlander.com/content/transplant/? 

GETTING THE CALL
Getting The Call For A Transplant

Once an organ becomes available and you receive that long awaited call or page from the transplant office, things will start to happen very, very quickly and you will understand why all that preparation and planning was so important.
It is essential for you and your family to stay calm and listen closely to the instructions given to you by the transplant coordinator.
Although the instructions may vary depending on the situation, you will generally be told to:
Do not eat or drink anything unless told otherwise.
Bring all of your current medications with you and a list of any known allergies
Bring your insurance card with you.
Bring only those personal items that are absolutely necessary (bring the patient and/or family pre-packed suitcase(s) [see Be Prepared]).
Be prepared to leave for the hospital immediately unless instructed otherwise by the coordinator
Notify the transplant office immediately if there are any delays, such as a the car breaking down or missing the plane.
Be prepared for a disappointment. Sometimes unexpected events occur that make proceeding with the transplant impossible, such as an infection or the development of additional medical problems in the recipient or a problem with the donor organ making it unsuitable for transplantion.

ARRIVING AT THE HOSPITAL

Pre-Operative Preparation

Once at the hospital you will be seen and examined by a member of the transplant team and additional pre-transplant preparation will be done. The following procedures may vary slightly, depending on the transplant center and the organ being transplanted:
Blood and urine tests
Chest x-ray and EKG
Enema
Chest and abdomen are shaved
Intravenous line (IV) is inserted for fluids and medications
Some medications are given orally and some are given intravenously
If you have not already done so, you will be asked to sign a surgical consent form
Some states, hospitals and/or transplant programs require separate consent forms for blood transfusions.
If you have any questions that you have not already discussed with your transplant surgeon, you should do so at this time.

The exact time that you are taken to surgery is coordinated with the expected arrival time of the donor organ. As this time grows closer, you will be taken to the operating room where the OR nurses and the anesthesiologist will continue your pre-operative preparation. It is normal to be anxious, so you will be given some medication to help you relax prior to going into surgery. You will still be awake when you arrive in the operating room. Once on the operating table:
You will be connected to a heart monitor and machines that monitor your blood pressure and the oxygen in your blood.
After you are totally asleep, a breathing tube will be inserted into your throat and connected to a ventilator (breathing machine) that will breath for you throughout the surgery and afterward until you are strong enough to breath on your own again.
Additional intravenous catheters will be inserted to help monitor heart and lung function and to provide vein access for fluids, blood, and medications.
A catheter will be placed in your bladder to keep an accurate record of how much urine your kidneys are making.

The Family During Surgery:
Family and friends will be instructed as to where they should wait during the surgery. The length of the surgery depends on many factors including the type of organ transplant, the patient’s individual anatomy, previous transplant(s) or other surgery, infections or scarring in the area. Kidney transplant generally takes the least amount of time and liver takes the longest. The transplant surgeon will give the family an idea of the expected time frame. Although procedures at each transplant center will vary, usually the transplant coordinator, operating room nurse, or member of the transplant team will provide the family with periodic updates on how the surgery is progressing. This may be done in person or by a phone call. It is important for the family to always make sure that the transplant team knows how and where to find them.

*from downloadable file on wordpad- "Waiting for Transplant" at
http://www.stadtlander.com/content/transplant/? 
 

The New England Organ Bank (NEOB) will not tell you the position that
you are on the transplant waiting list. We will not release this information
to you for a number of reasons, which I will delineate below. But first, I
would like to make a couple of important points.

* We WILL release the information to your transplant surgeon, and I
always refer patients to them. Call your surgeon and have him/her call us for
the information. We will gladly release the information to them.

* Our policy may not speak universally for all organ banks (though I
hope that it does), but I know that UNOS will not give out the information to
the individual candidates either. The reasons follow:

1) Patient confidentiality.
By releasing your location on the list, we could compromise
the confidentiality of other patients. Also, although we do
know the voice of the tx. surgeons, we don't know yours...and
we wouldn't want an unscrupulous person breaching your personal
and confidential medical information.

2) Doctor - Patient relationship.
Your doctor may have you temporarily inactive or listed at a
certain status for numerous reasons that you may be unaware
of. If we were to see that you were not "on the list" on a
particular day, without knowing all of the intricate
details of your medical care, misunderstandings could ensue.

3) Mechanics of candidate lists.
There are a number of factors that go into your "exact" position
on the transplant candidate lists. You could be 20th, but be of
a size that is the ONLY match for a dwarf or giant. Telling the
position as a definitive number can be very misleading, and it is
important for your surgeon to explain this to you.

I personally think the most important of these is the confidentiality
issue. We value the confidential nature of the work we do, and do everything
we can to protect patient privacy. This explains why we will only send thank
you letters to donor families anonymously, discourage recipients meeting donor
families without mutual consent, and not release patient information of ANY kind
to anyone other than a recognized transplant surgeon.
Andrew H. Wheelock E-mail: awhee@neob.com
New England Organ Bank Phone: 800-446-6362
One Gateway Center
Newton, MA 02158
===============================================================

An additional response from Joel Newman at UNOS...

Good response from Andrew Wheelock. I'd only amplify one point and
add a couple more from our perspective.

> There are a number of factors that go into your "exact" position
> on the transplant candidate lists. You could be 20th, but be of
> a size that is the ONLY match for a dwarf or giant. Telling the
> position as a definitive number can be very misleading, and it is
> important for your surgeon to explain this to you.

Candidates and donors are matched by data, not rank. The only thing
you could be "ranked" by, in theory, is your waiting time. You could
be #1 on your local list by waiting time, having waited longer than
everyone else. However, if you're blood type B and a type A organ
comes along, you'd automatically be excluded. The same is true for
organ size, tissue match, etc. Given that all donors and all
candidates differ in some respects, you could be 20th on the list for
one offer, 3rd for the next, then 57th, then 1st.

Even if you're at the "top of the list," you may not get the organ.
Perhaps you have a complication that would preclude getting a
transplant for a few days or weeks. Maybe in reviewing the lab work
or donor history the transplant team has cause to defer the offer.
Perhaps, if you're highly sensitized, the initial crossmatch is OK but
the final crossmatch comes back bad. There are lots of scenarios.
Any refusals and the explanations would be submitted to UNOS.

Organs other than kidneys are most often transplanted into one of the
first 10 candidates identified on the match run. For kidneys that
rate is much lower, particularly because of highly sensitized patients
with adverse crossmatches.

With specific, written permission from the patient and from the
listing center, UNOS can provide the basic information on patient
listing (date of entry, current medical status, etc.). But I'd *beg*
you to call the center first on this if you have any questions! And
again, for all the reasons above, this would be meaningless as an
expression of your "rank" for a transplant.
* Joel D. Newman
* Manager, Corporate Communications
* United Network for Organ Sharing (UNOS)
* E-mail: newmanjd@comm5.unos.org
* Ph: (804) 330-8561

http://www.transweb.org/qa/qa_txp/faq_pos_list.html 

 

Pretransplant Issues

from Manual of Liver Transplant Medical Care

http://www.medscape.com/viewarticle/433314_1

Indications
A liver transplant is indicated for liver failure, whether it is of acute onset or chronic. Liver failure is signaled by a number of clinical symptoms (e.g., ascites, variceal bleeding, hepatic encephalopathy, malnutrition) and by biochemical (laboratory) test results that suggest impaired hepatic synthetic function (e.g., hypoalbuminemia, hyperbilirubinemia, coagulopathy). The cause of liver failure often influences the clinical presentation. For example, patients with acute liver failure generally present with hepatic encephalopathy (HE) and coagulopathy, whereas patients with chronic liver disease (CLD) most commonly present with ascites, gastrointestinal (GI) bleeding, and malnutrition.
Specific indications for liver transplantation are also influenced by whether the liver failure is of acute or chronic onset. Acute liver failure is not as common and is discussed later in this chapter. Indications for a liver transplant evaluation in patients with CLD are as follows:

CLINICAL INDICATIONS BIOCHEMICAL INDICATIONS
Recurrent or severe hepatic encephalopathy (HE) Serum albumin <3.0 g/dL
Refractory ascites Serum international normalized ratio (INR) >1.7
Spontaneous bacterial peritonitis (SBP) Serum bilirubin >2 mg/dL (>4 mg/dL for cholestatic disorders)
Hepatorenal syndrome (HRS)
Significant weakness, fatigue, or progressive malnutrition
Recurrent cholangitis or severe pruritus
Progressive bone disease
Recurrent variceal bleeding

A.1. Hepatic encephalopathy
In its early stages, hepatic encephalopathy (HE) may manifest as subtle disturbances in sleep, depression, and emotional lability. Increasing severity of HE is indicated by progressive somnolence, altered speech, and at the extreme end, coma. Physical examination is significant for the typical flapping tremor of asterixis, and blood tests often reveal an elevated serum ammonia level. Hepatic encephalopathy may occur spontaneously, but it is more commonly triggered by a precipitating factor such as spontaneous bacterial peritonitis, gastrointestinal bleeding, constipation, use of sedatives, or excessive dietary protein intake.

A.2. Ascites
Ascites is generally associated with portal hypertension. The initial approach to the management of ascites is sodium restriction and diuretic therapy. If this approach is not successful, patients may require repeated large-volume (4 to 6 L) paracentesis. A better option for managing diuretic-resistant ascites requiring frequent paracentesis is transjugular intrahepatic portosystemic shunting (TIPS). A potential complication of TIPS is progression of liver failure or disabling encephalopathy. Patients with signs of far-advanced liver disease (e.g., hyperbilirubinemia, hepatic encephalopathy, renal dysfunction) are generally not good candidates for TIPS.

A.3. Spontaneous bacterial peritonitis
This complication of chronic liver failure generally signals advanced disease and tends to be recurrent. Aerobic gram-negative bacteria account for 60% of the cultured organisms; gram-positive cocci account for the remainder. The diagnosis is confirmed if ascitic fluid obtained from a peritoneal tap has a neutrophil count >250/mL. The patient generally is treated with a third-generation cephalosporin. The transplant should be deferred until at least 48 hours after the initiation of antibiotic therapy.

A.4. Portal hypertensive bleeding
The likelihood of patients with chronic liver disease and cirrhosis developing gastroesophageal varices ranges from 35% to 80%. About one-third of these patients will experience bleeding from these varices, and the risk of recurrent bleeding approaches 70% by 2 years after the index bleed. Each bleeding episode is associated with a 30% mortality rate. Thus, urgent treatment of the acute hemorrhage and steps to prevent rebleeding are essential.
Endoscopy is indicated to diagnose and treat the acute bleeding with either band ligation or sclerotherapy. Other therapies include vasoactive drugs (e.g., octreotide, vasopressin), balloon tamponade, transjugular intrahepatic portosystemic shunting (TIPS), and emergency surgical procedures such as surgical portosystemic shunts or transection of the esophagus. Generally, patients whose endoscopic procedures fail to control the bleeding should undergo emergency TIPS, if feasible. Beta-blockers have been shown to be of value in preventing both the first episode of bleeding in patients with varices (index bleed) and rebleeding.

A.5. Hepatorenal syndrome
In patients with advanced liver disease and ascites, hepatorenal syndrome (HRS) manifests as oliguria (<500 mL of urine/day) associated with low urine sodium levels (<10 mEq/L). It is a functional disorder, so the kidneys have no structural abnormalities and the urine sediment is normal. The differential diagnosis includes acute tubular necrosis, drug nephrotoxicity, and chronic intrinsic renal disease. Hepatorenal syndrome may be precipitated by volume depletion from diuresis, spontaneous bacterial peritonitis, or agents such as nonsteroidal antiinflammatory drugs. Patients may require dialysis support, but the only effective treatment is liver transplantation.

A.6. Chronic fatigue
Severe weakness or fatigue may sometimes be the primary symptom of advanced liver disease. Such weakness can be debilitating, leading to the inability to work or even carry out day-to-day activities.

A.7. Malnutrition and muscle wasting
Advanced liver disease is often associated with some degree of malnutrition and muscle wasting; avoiding rigid dietary protein restriction (especially in patients without hepatic encephalopathy) and having the patient eat small frequent meals can minimize these events.

A.8. Biochemical abnormalities
As liver function worsens, hepatic synthetic function deteriorates. Laboratory evidence of this loss of synthetic function may include a low serum albumin level, a high serum bilirubin level, and, in the case of blood clotting abnormalities, a rise in the serum international normalized ratio (INR).

Diseases Treatable by Liver Transplantation
A host of diseases are potentially treatable by liver transplantation (see Table 2), including chronic liver diseases, hepatic malignancies, and fulminant (acute) liver failure.

B.1. Chronic liver diseases
B.1.a. Cholestatic disorders. Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are the most common cholestatic disorders that lead to liver failure in adults. Primary biliary cirrhosis is a disorder involving destruction of the interlobular bile ducts. It can progress to cirrhosis and liver failure over several decades and most commonly affects middle-aged women. Primary sclerosing cholangitis is a disease characterized by inflammatory injury to the intrahepatic and extrahepatic bile ducts. It occurs mostly in young men, 70% of whom have inflammatory bowel disease. Biliary atresia is the most common cholestatic disorder in children. It is a destructive inflammatory condition of the bile ducts, which, left untreated, usually results in death within the first or second year of life.
B.1.b. Chronic Hepatitis. Hepatitis C and B are the most common causes of chronic hepatitis that leads to liver failure. Progression from a state of chronic infection to cirrhosis is generally slow, usually taking 10 to 20 years. However, chronic alcohol abuse accelerates this process, especially in patients with hepatitis C. Autoimmune hepatitis is of unknown cause, affects primarily women, and can present either acutely over months or insidiously over years.

B.1.c. Alcoholic Liver Disease. Alcoholic liver disease is the most common cause of end-stage liver disease (ESLD) in the United States. These patients are generally suitable candidates for a liver transplant provided an adequate period of sobriety can be documented.

B.1.d. Metabolic Diseases. A variety of metabolic diseases may lead to progressive liver injury and cirrhosis, including hereditary hemochromatosis, alpha1-antitrypsin deficiency, and Wilson's disease. Hereditary hemochromatosis is an autosomal codominant disorder characterized by the chronic accumulation of body iron; its deposition in parenchymal organs may lead to cirrhosis, cardiomyopathy, and endocrine disorders including diabetes. Alpha1-antitrypsin deficiency is an autosomal recessive disorder characterized by abnormally low levels of this protease inhibitor. Patients may develop cirrhosis at any age, but it usually occurs during the first or second decade of life. Wilson's disease is an autosomal recessive disorder of copper excretion characterized by the accumulation of toxic levels of copper in various tissues and organs. Patients may present either with fulminant hepatic failure or chronic hepatitis and cirrhosis.

B.2. Hepatic malignancy
Hepatocellular carcinoma (HCC) may complicate cirrhosis of any etiology, but it most commonly occurs in patients with hepatitis B, hepatitis C, hemochromatosis, or tyrosinemia. These patients generally are not candidates for surgical resection due to the underlying diseased liver. Liver transplantation may be an option for these patients. The best candidates for a liver transplant are patients with a single lesion less than 5 cm in diameter or in those with no more than 3 lesions, the largest of which is no greater than 3 cm in diameter. Posttransplant recurrence rates are exceedingly high in patients whose lesions do not meet these criteria. Exceptions include patients with a large fibrolamellar hepatoma, who generally do well after transplantation.

B.3. Fulminant hepatic failure
Fulminant hepatic failure (FHF) is defined as the development of hepatic encephalopathy (HE) and profound coagulopathy shortly after the onset of symptoms such as jaundice in patients without preexisting liver disease. The most common causes of FHF include acetaminophen overdose, acute hepatitis B, various drugs and hepatotoxins, and Wilson's disease; often no cause is identified. Treatment consists of appropriate critical care support, providing patients time for spontaneous recovery, if it is to occur.
The likelihood of spontaneous recovery from FHF depends on the patient's age (those younger than 10 and older than 40 years have a poor prognosis), the underlying cause, and the severity of the liver injury (as indicated by degree of HE, coagulopathy, and renal dysfunction). Poor prognostic signs suggesting a low likelihood of spontaneous recovery, and hence situations in which liver transplantation should be considered, are shown in Table 3. A subset of patients may experience a delayed onset of hepatic decompensation (coagulopathy and encephalopathy), which occurs 8 weeks to 6 months after the onset of symptoms such as jaundice. This condition is often referred to as subacute hepatic failure; these patients rarely recover without a transplant.

B.4. Other diseases
A host of other diseases may lead to liver failure requiring a transplant, including Budd-Chiari syndrome and polycystic liver disease. The former involves thrombotic obstruction of the hepatic veins, which leads to hepatic congestion, ascites, and eventually, liver damage. Polycystic liver disease involves a large number of cysts, which, depending on their size, can lead to debilitating symptoms.

Contraindications
Few absolute medical or surgical contraindications to liver transplantation exist. However, uncontrolled systemic infection is one obvious contraindication to transplantation.
We have no specific age limit, but patients must have adequate cardiac and pulmonary function. Although coexisting coronary artery disease is uncommon, patients with cirrhosis may develop significant hypoxia and pulmonary hypertension; those with severe hypoxemia or right atrial pressures greater than 60 mm Hg rarely survive a liver transplant.

Patients with hepatocellular carcinoma and metastatic disease, obvious vascular invasion, or a significant tumor burden are not good transplant candidates. Transplantation should be deferred in patients with an extrahepatic malignancy until at least 2 years after completion of curative therapy.

Portal vein thrombosis is not a contraindication to liver transplantation, yet some viable splanchnic venous inflow must be present. If the entire portal venous system is occluded, attempts at a transplant are rarely successful.

Ongoing substance abuse is the most commonly encountered contraindication to liver transplantation. Before considering a patient for a transplant, most centers (including ours) require 6 months of abstinence, demonstration of compliant behavior, and willingness to enroll in a chemical dependency program.

Timing
Timing of the transplant -- from the time of the initial referral, to being listed on the waiting list, to the actual surgery -- can have a profound impact on outcome. The prognosis is generally excellent in patients who undergo transplantation before multisystem complications of end-stage liver disease have a chance to develop. However, in severely debilitated patients, posttransplant survival decreases by 20% to 30%.
Patients with cirrhosis should be referred for a liver transplant when they develop evidence of hepatic synthetic dysfunction, experience their first major complication (e.g., ascites, variceal bleed, spontaneous bacterial peritonitis, hepatic encephalopathy), or develop malnutrition. Delaying referral until patients have developed intractable ascites or hepatorenal syndrome frequently results in death before transplantation can even occur. The Child-Turcotte-Pugh (CTP) score is a valuable tool for assessing disease severity (Table 4). A cumulative score of 7 meets the minimal listing requirement for a liver transplant, so patients with CTP scores of 7 or greater should be referred for transplantation.

Patients with hepatocellular carcinoma and cirrhosis should be referred for liver transplantation as soon as the tumor is discovered.

Patients with fulminant hepatic failure can deteriorate rapidly; therefore, these patients should be referred for transplantation as soon as the diagnosis is suspected (e.g., presence of persistently elevated international normalized ratio [INR] or alteration in mental status).

Pretransplant Evaluation and Management
A detailed evaluation is carried out prior to deciding whether a patient is a candidate for liver transplantation. A significant portion of this evaluation can be performed at the referring medical facility, but certain tests must be done at the Transplant Center. Components of this evaluation include consultations, laboratory tests, and other clinical studies.

E.1. Consultations
The candidate will meet the following people during the pretransplant evaluation:

Transplant surgeon.

Transplant hepatologist.

Transplant coordinators.

Social worker.

Dietician.

Financial representative.
Consultation with other healthcare professionals may be arranged, if necessary.

E.2. Laboratory tests
The following laboratory tests are included in the pretransplant evaluation:

Complete blood count (CBC).

Chemistry profile including electrolytes, blood urea nitrogen (BUN), creatinine (Cr).

Complete liver function tests, including serum liver enzymes, bilirubin, albumin, and international normalized ratio (INR).

Alpha-fetoprotein level (to screen for hepatocellular carcinoma).

Viral serology tests, including those for hepatitis A, B, and C; cytomegalovirus (CMV); Epstein-Barr virus (EBV); and human immunodeficiency virus (HIV).

ABO blood group typing.

E.3. Other tests
Other tests included in the pretransplant evaluation are as follows:

Chest radiograph (x-ray).

12-lead electrocardiogram (ECG).

Dobutamine echocardiogram (if age >55 years, history of cardiac disease, or significant risk factors for cardiac disease).

Ultrasound study of the liver with Doppler (to assess blood flow to the liver and to rule out portal vein thrombosis or mass lesions).

Pulmonary function tests (if significant smoking history or history of asthma).

Colonoscopy.

E.4. Underlying medical problems
Pretransplant care involves optimizing the patient's overall medical status and addressing problems (related and unrelated to the liver failure) that may affect the postoperative course. Medical problems and treatments may differ for individual patients, depending on the etiology and chronicity of their liver failure. Yet a systematic approach, covering all major organ systems, should be used to ensure that no major problems are overlooked. All respiratory, cardiovascular, neurologic, renal, gastroenterologic, hematologic, and metabolic concerns should be addressed.
Patients with chronic liver failure may be stable and awaiting transplant at home or deteriorating to the point that they require intensive monitoring in a critical care setting. Clinical problems may be related to the failing liver itself or to its effect(s) on other organ systems; in addition, medical problems unrelated to the liver failure may exist.

E.4.a. Respiratory conditions. Frequently, attention needs to be directed toward the lungs. Respiratory complications are common postoperatively, and some preexisting pulmonary problems may complicate or preclude transplantation.

Patients with end-stage liver disease may have impaired gas exchange due to a ventilation-perfusion mismatch, atelectasis secondary to ascites, or intrapulmonary arteriovenous shunts. Shunts may lead to severe hypoxemia, especially when patients are in the upright position (orthodeoxia). A transplant may be contraindicated if intrapulmonary shunting is severe, as manifested by hypoxemia that only partially improves with high inspired oxygen concentrations (e.g., arterial oxygen tension [PaO2] less than 200 mm Hg for inspired oxygen concentration [FIO2] = 100%).

Other causes of respiratory difficulties in patients with chronic liver failure include chronic ascites, pleural effusion, depleted skeletal muscle mass from poor nutrition, and obstructive lung disease from long-term smoking. Drainage of pleural effusions and aggressive treatment of ascites may provide some relief. Cessation of smoking and aggressive bronchodilator and antibiotic therapy, as indicated, are essential to decrease the risk of postoperative pulmonary infection.

E.4.b. Cardiovascular conditions
A hyperdynamic cardiac state, as manifested by an increased cardiac index and decreased systemic vascular resistance, is found in two-thirds of patients with cirrhosis. It may represent a compensatory state intended to maintain the delivery of oxygen to peripheral tissues; hence, preoperative attempts to depress the myocardium to achieve normal hemodynamic indices are not indicated.
Atherosclerosis may be less prevalent in patients with cirrhosis, but the possibility of underlying coronary artery disease should be considered, especially in older patients. Other conditions to consider include cardiomyopathy (which may be associated with alcoholic liver disease, amyloidosis, or hemochromatosis), valvular pathology, and pulmonary hypertension. A preoperative echocardiogram is most useful in detecting these conditions.

The presence of severe pulmonary hypertension (pulmonary arterial systolic pressure greater than 60 mm Hg) that does not reverse with vasodilator therapy represents a contraindication to liver transplantation.

E.4.c. Neurologic conditions
Most preoperative neurologic problems are secondary to hepatic encephalopathy (HE); this neuropsychiatric disorder likely reflects the accumulation of toxic products not cleared by the diseased liver. Manifestations of HE may be divided into four clinical stages based on severity: stage I, mild confusion and agitation; stage II, drowsiness and disorientation; stage III, depressed arousability and profound confusion or disorientation; and stage IV, coma. Exacerbating factors -- gastrointestinal bleeding, excessive dietary protein intake, and infections such as spontaneous bacterial peritonitis -- should be properly treated. Patients with stage III and IV HE may require intubation for airway protection. Cerebral edema with increased intracranial pressure (ICP) is more common in patients with fulminant hepatic failure as opposed to those with chronic liver disease.

E.4.d. Renal conditions
Renal and electrolyte problems are common in patients with liver failure, as liver and renal diseases often coexist. Whereas a number of potential causes exist, these problems are usually due to prerenal factors (e.g., hypovolemia, diuretic use), acute tubular necrosis (ATN), nephrotoxic drugs (e.g., aminoglycosides, amphotericin B), raised intraabdominal pressure from massive ascites, and hepatorenal syndrome (HRS). The development of HRS indicates rapid hepatic deterioration and is an indication for urgent liver transplantation. Another possible cause of renal dysfunction is glomerulopathy due to a large number of circulating immunoglobulin complexes associated with the underlying liver disease, most commonly hepatitis C.
Compared to patients with no renal dysfunction, those with HRS or renal failure of any cause have worse posttransplant outcomes. Therefore, all attempts to avoid or reverse any renal dysfunction must be made prior to transplantation. Once the cause of the renal insufficiency is established, appropriate therapy should be initiated as indicated. Treatment may include optimization of the patient's volume status via invasive monitoring, large-volume paracentesis, cessation of nephrotoxic drugs, administration of nonpressor doses of dopamine, and the judicious use of diuretics. If this therapy is unsuccessful, dialysis support may be required until a donor organ becomes available.

E.4.e. Other conditions
The pretransplant workup also should include an assessment of the patient's gastrointestinal tract, hematologic system, and nutritional status. Gastrointestinal bleeding may be a significant problem before transplantation, requiring urgent diagnosis and treatment. Blood clotting abnormalities may be extensive due to malabsorption of vitamin K and decreased production of several coagulation and anticoagulation factors. The nutritional status of these patients is often poor, with severe loss of muscle and fat stores and significant catabolism of protein. Patients may be unable to tolerate a high protein intake, especially those with hepatic encephalopathy; branched-chain amino acids may be an option in such patients.

E.5. Chemical dependency
A history of alcohol or drug abuse is common in liver transplant candidates. Before considering such patients for transplantation, documented abstinence is important. We will not evaluate patients with a history of alcohol abuse until at least 6 months of abstinence is documented. Also, they must undergo a chemical dependency evaluation to carefully screen for any evidence of ongoing substance abuse or risk factors that may lead to posttransplant recidivism. A documented period of abstinence of at least 1 year is required by our center before actually proceeding with the transplant.

E.6. Patients with hepatocellular carcinoma
Transplant candidates with hepatocellular carcinoma and cirrhosis must undergo careful radiologic imaging prior to transplantation to ensure that their disease meets certain criteria. Magnetic resonance imaging (MRI) of the liver is used to assess the size and number of lesions as well as any evidence of vascular involvement. Other tests are performed to rule out metastatic disease.
Candidates with tumors often will undergo radiofrequency ablation (RFA). This technique involves local control of the tumors with heated probes, inserted percutaneously or via laparoscopy. Radiofrequency ablation may limit tumor growth and prevent tumor spread while the candidate is on the transplant waiting list.

E.7. Reevaluation on waiting list
While the transplant candidate is on the waiting list, routine follow-up is essential to assess the course of the disease, adjust his or her medical status if necessary, and address any new medical problems. In candidates with hepatocellular carcinoma, routine imaging studies are necessary to monitor tumor growth. All candidates should be reevaluated at least every 3 months. It is very important for referring physicians and medical facilities to notify the Transplant Center if the candidate's condition significantly deteriorates, if secondary complications or new medical problems develop, or if hospitalization is required. Notification is especially important if the candidate develops life-threatening complications or is admitted to an intensive care unit, as these events might allow for a change in medical status or for an urgent transplant.

E.8. Fulminant hepatic failure
Generally, patients with fulminant hepatic failure (FHF) are more acutely ill than those with chronic liver failure, and thus require more intensive pretransplant care. Patients with FHF have more severe hepatic parenchymal dysfunction, as manifested by coagulopathy, hypoglycemia, and lactic acidosis. In addition, infectious complications are more common in these patients, as are renal failure and neurologic complications, especially cerebral edema.

Coagulopathy is usually secondary to the impaired hepatic synthesis of blood clotting factors. Disseminated intravascular coagulation (DIC) may cause consumption coagulopathy in patients with severe systemic illness.

Hypoglycemia is more likely to occur in patients with FHF, so the serum glucose level should be closely monitored. Intravenous glucose should be administered at a sufficient rate to maintain euglycemia.

Bacterial infections are common in patients with FHF, a reflection of the loss of the liver's immunologic function. The respiratory and urinary systems are the most common sources of infection. In addition, almost one-third of these patients develop some form of fungal infection, usually secondary to Candida species. Sepsis is generally a contraindication to transplantation; if it is unrecognized prior to transplantation, the outcome is poor.

Multiple organ dysfunction syndrome (MODS), characterized by adult respiratory distress syndrome (ARDS), renal failure, increased cardiac output (CO), and decreased systemic vascular resistance (SVR), is a well-described complication of FHF. It may be due to the impaired clearance of vasoactive substances by the liver, and the associated hemodynamic abnormalities may manifest as hypotension and worsening of tissue oxygenation. Pretransplant mechanical ventilation and dialysis support may become necessary in these patients.

Cerebral edema is substantially more common in patients with FHF. As many as 80% of patients who die of FHF have prior evidence of cerebral edema. Although its pathogenesis is unclear, it may be due to the accumulation of potential neurotoxins that are normally cleared by the liver. The diagnosis of cerebral edema may be tricky; patients are often sedated and ventilated, making clinical examination difficult. Radiologic imaging is also not sensitive or specific for cerebral edema. Thus, several centers have tried intracranial pressure (ICP) monitoring.
With the use of ICP monitoring, therapy for cerebral edema (e.g., mannitol, hyperventilation, thiopental) can be directed toward achieving an adequate cerebral perfusion pressure (>50 mm Hg). Such monitoring also helps predict the likelihood of posttransplant neurologic recovery. Sustained cerebral perfusion pressures of less than 40 mm Hg have been associated with postoperative neurologic death. Disadvantages of ICP monitoring include the risks of performing the procedure in a patient with severe coagulopathy, possible infection, and the potential for precipitating an intracranial hemorrhage.

Waiting Time and United Network for Organ Sharing (UNOS) Status
The length of time on the transplant waiting list depends on several factors, including blood type, size, and medical status. Of these, medical status (i.e., severity of illness) is the most important factor. Status 1 candidates have the highest priority, followed by Status 2A, Status 2B, and Status 3 candidates. Status 7 candidates are currently on hold. Descriptions of these candidate UNOS statuses are as follows (also see Table 5):

Status 1 includes candidates with fulminant hepatic failure (FHF), any critically ill pediatric patients in an intensive care unit (ICU), and recipients who develop hepatic artery thrombosis (HAT) or primary (graft) nonfunction within 7 days after transplantation. These patients have a life expectancy without transplant of less than 7 days.

Status 2A includes candidates with chronic liver disease (CLD) who are critically ill and in an ICU with a life-threatening complication. These patients have a Child-Turcotte-Pugh (CTP) score greater than or equal to 10 and meet at least one of the following medical criteria: documented, unresponsive, active variceal hemorrhage; hepatorenal syndrome; refractory ascites/hepato-hydrothorax; or advanced hepatic encephalopathy.

Status 2B includes patients with advanced CLD as indicated by a CTP score greater than or equal to 10 or by a CTP score greater than or equal to 7 plus 1 of the following medical criteria: documented, refractory, active variceal hemorrhage; hepatorenal syndrome; spontaneous bacterial peritonitis; or refractory ascites/hepato-hydrothorax. Additional medical criteria in pediatric patients include recurrent cholangitis and growth failure. Suitable candidates with known hepatocellular carcinoma also may be listed as Status 2B, regardless of their CTP score.

Status 3 includes candidates with CLD that is less advanced but who still require continuous medical care. These patients have a CTP score greater than or equal to 7 but less than 10.

Status 7 includes candidates who have been approved for transplantation but are currently on hold due to some unresolved issue (i.e., temporarily inactive).
These are the status categories currently used for liver allocation. However, this method is to be replaced by a different method of allocation in the very near future. The new method of allocation will be based on the MELD (Model for End-Stage Liver Disease) score of individual adult patients. The MELD score is calculated from a mathematical equation that incorporates the patient's bilirubin level, international normalized ratio (INR), and creatinine level. A companion formula for children, the PELD (Pediatric End-Stage Liver Disease Model), will be used to guide liver allocation in patients younger than 18 years of age.

Few patients are able to pay all of the costs of transplantation from a single source. This section describes financial resources and some of the more common ways transplantation is funded.

Most likely, you will have to rely on a combination of funding sources. For example, you may be able to finance the transplant procedure through insurance coverage and pay for other expenses by drawing on savings accounts and other private funds or by selling some of your assets. It's a good idea to keep your transplant center social workers and financial coordinators informed of your progress in obtaining funds.
 

COSTS

Transplant costs include:

• transplant evaluation and testing;
• transplant surgery;
• follow-up care, lab tests and medication

Even before the transplant, these costs add up quickly. One of the biggest expenses is related to time spent in the hospital's intensive care unit (ICU). The ICU is staffed by critical care nurses and is equipped to monitor and treat critically ill patients. Patients are generally taken to the ICU after the transplant operation, but some are also treated in the ICU before the transplant.

Other costs directly associated with transplantation include:

• fees for transplant surgeons and operating room personnel;
• anesthesia;
• recovery and in-hospital stay; and
• extensive lab tests.

In addition, other expenses incurred prior to or following the operation include:

• charges for evaluating and accepting a patient for transplant;
• recovery of the organ from the donor;
• transportation to and from the transplant center -- not only for the transplant, but for patient evaluation and check-ups;
• food and lodging for family members while the patient is hospitalized;
• laboratory tests;
• child care;
• physical or occupational therapy and other rehabilitation; and the cost of anti-rejection drugs and other medications, which can easily exceed $10,000 per year. These drugs are required for the rest of the recipient's life.

If you are travelling any distance to receive your transplant, remember to consider the cost of food, lodging and transportation. The cost of food and lodging for your family while you are in the hospital can vary greatly from city to city. Some centers offer family lodging at reduced or no cost, while other centers do not. More than likely, these expenses will not be covered by insurance.

There may also be lost earnings if your employer does not pay for the time you or your spouse spend away from work.

Estimated Charges for Organ & Tissue Transplantation

Below is an ESTIMATE of the first-year and subsequent follow-up charges associated with a liver transplant. Your transplant could cost much less or much more, depending on how many of the services are included in your bill and the area in which your transplant takes place. (These estimates are based on 1996 Dollars and will be higher now).

1st Year Charge:

• $314,500  (this is estimated at approx. $500,000 in 1998)

Annual Follow-up Charges:

• $21,900

Financing

    Usually, insurance companies will pay about 80 percent of your hospital charges. This means that you are responsible for the remaining 20 percent from other sources until you reach your "out-of-pocket" limit. Be sure to pay your premiums so that your policy will not lapse.
    Most insurance policies have some sort of lifetime maximum amount, or "cap." After a patient has reached this amount, the insurance company does not have to pay any additional benefits. The amount of the cap varies greatly, depending on the individual policy. The cap may apply to just one procedure or treatment or to all combined procedures and treatments. Even after the actual transplant, the ongoing cost of care may exceed the cap, so it is important to be familiar with the amount and terms of your insurance cap and how your insurance dollars are spent.
    Some insurers consider certain transplant procedures "experimental" or "investigational" and do not cover these cases. If you have any doubts about how your coverage is determined, contact your insurance company. If you still have questions, contact the office of your State Insurance Commissioner. Many companies require prior authorization (approval) for organ transplant procedures. Make certain that you are not in a waiting period for coverage for conditions you may have had before joining the insurance plan. Delays in insurance payments can cause you unnecessary stress, so make arrangements with your insurance company prior to the transplant. Transplant center social workers and financial coordinators will help you with the information you need to complete this process.
    You may want to seek help from an advocacy or charitable organization or a legal advisor to negotiate with your insurer. For example, if the company does not wish to cover your transplant, you may be able to prove that it has covered similar procedures in the past, or that a transplant would be more cost-effective than your current care (especially in the case of dialysis). If you can, you may have a better chance of getting coverage for your particular case.
    If you are insured by a group health plan (medical, dental or vision) through your place of work and you must leave your job or have your work hours reduced, you and your family may qualify for extended coverage through COBRA.
   Government funding for families of active duty, retired or deceased personnel may be available through the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS). CHAMPUS shares the cost of heart, lung, heart-lung, liver, kidney and combined liver-kidney transplants for patients with end-stage organ disease. Patients must receive pre-authorization from the CHAMPUS medical director and meet CHAMPUS selection criteria. Pre-authorization is based on a narrative summary submitted by the attending transplant
    Veterans of the Armed Forces who first became ill while in service or who are indigent as defined by the Veterans Administration (VA) may be eligible to receive a transplant at a VA Medical Center. Some veterans may also receive medications funded by the VA. For further information, contact your local VA office or your nearest VA Medical Center.

   Charitable organizations offer different types of support. Some provide information about diseases of certain organs or about a particular type of transplant and encourage research into these diseases and treatments.
    Other groups provide limited financial assistance through grants and direct funding. However, it is very unlikely that one group can cover all of the costs for an individual patient. An organization may have limits on using available funds, and may only be able to help with direct transplant costs, food and lodging or medication costs.

    Advocacy organizations advise transplant patients on financial matters. They should be abl to provide supporting information and background documentation to prove that they are legally recognized to help those in need.

    Patients and families often use public fund raising to help cover expenses not paid by medical insurance. This may be a key source for financing transplantation.
    Proceed with caution and plan carefully before you begin, as there are many legal and financial issues to consider. For example, if you and your family have been accepted for Medicaid benefits and funds are raised for you, the donated money could be counted as income, and you may then lose your eligibility.


http://www.geocities.com/1leighann/Financial.html

SOURCE:  UNOS  Copyright © 1998, United Network for Organ Sharing
 

Financial Help For Transplants:

http://www.transplantfund.org/
http://www.transplants.org/
http://www.trioweb.org/