British Columbia Transplant Society Website

History of Liver Transplantation

The first successful human liver transplant was performed in 1976 by Dr.Tom Starzl and his group, but the procedure did not receive widespread acceptance in medical practice until the early 1980's.

The discovery of two new immunosuppressives, Cyclosporin and Monoclonal antibodies, in the early 1980's, set the tone for a new era in liver transplantation. Along with the discoveries in medicine, surgical techniques improved dramatically. The ability to preserve donor organs for an extended period of time also contributed to the success that liver transplant recipients enjoy today.

The first liver transplant in BC was performed in 1989. Since then, more than 300 British Columbians have received a liver transplant. In 2001, BC Transplant established a Living Donor Liver Program, the first of these transplant was performed in March 2001. Click here for more information about Living Liver Transplants.

How your liver works

The liver weighs about 3 pounds and is divided into 4 sections, called lobes.

The liver is an important passage way for substances moving along from the stomach to the intestines, and finally to the blood stream. Where food is concerned, your liver transforms food into many chemical parts for use in other parts of the body. Some medicines are also changed by the liver. Your liver also stores sugar and vitamins so your body can use them when they're needed. In addition, your liver is a filtering station; it takes some waste and poisons out of your bloodstream.

The liver as a nourisher

The food we eat travels into the stomach and then on to the intestines. These organs break up the food into small pieces that can be absorbed into the bloodstream. However, about 90% of these small pieces go straight from the intestines to the liver. The liver then sends this nourishment into the bloodstream so that it can be distributed to the cells that need it.

As we said earlier, your liver also stores energy. Carbohydrates, for example, are sugars that your body uses to get quick energy. Your liver stores some of these sugars and releases them between meals whenever your cells need nourishment. This way, the liver makes it easy for you to keep going all day without eating each time you need more energy

Finally, your liver helps you digest fat and important vitamins stored in fat. Your small intestine cannot handle fat on its own, so your liver makes special substances called bile acids that break fat into pieces, almost the same way that dish detergent cuts through grease. Bile acids are necessary for you to absorb vitamins A, D, and E, all of which are found in fat. Your body uses each of these vitamins every day. Your liver stores other important vitamins, like vitamin B 12 and releases them as you need them.

The liver as a waste treatment system

Your body needs ways of getting rid of harmful chemicals, and the liver is very important in this process. Any time you take medicine, even an aspirin, it's your liver's job to later remove the medicine from your bloodstream. If your liver isn't functioning correctly, the medicine may stay in your bloodstream longer than it should, and that can cause problems.

Each time you take a drink of alcohol or use an illegal drug (like cocaine or marijuana), your liver goes to work filtering these substances out. The more alcohol or drugs you take, the longer it takes and the harder it is for your liver to get you back to normal again. People who drink too much or take too many drugs can do a lot of harm to their livers, sometimes to the point where the liver cannot heal.

Your body itself also naturally makes a lot of waste products. (Cells and organs are living factories, and they have "toxic waste" they need to get rid of.) Many of these wastes are poisonous and must be quickly broken down or they can cause harm to your heart, brain, kidneys, or other organs. Here again, the liver's ability to filter is important, and the liver is responsible for breaking down these waste products and making sure that they are sent either to the intestines or to the kidneys to be excreted.
Just as a factory takes different pieces of metal and builds them into a car, your liver takes natural chemicals such as proteins, carbohydrates, fats, and vitamins and makes them into substances your body needs. All our cells need different kinds of proteins to do different jobs (there are millions of proteins, and they can have very different effects in the body). Your liver takes these different proteins and reshapes them, either by cutting them into smaller pieces or assembling them into larger proteins so that they are just right for use by a particular part of the body. Your liver makes or breaks down thousands of different proteins every day.

Success for Liver Transplantation

Liver transplantation is excellent therapy for patients with end-stage liver disease. The one-year survival rate is approximately 85%. The suggestion is that patients that are doing well at the end of one year have the same outcome as the general population. While these patients will require immunosuppresants for the rest of their life, their quality of life is typically excellent.

Click here for patient and graft survival rates

Transplant Assessment

Although transplantation is considered an established form of treatment for end-stage organ failure, it is not suitable for everyone, so every potential transplant patient must be carefully assessed. The assessment phase starts when your specialist or family doctor refers you to the transplant team. Each referring specialist in BC has a copy of the Referral Guidelines for Liver Transplantation.

During the assessment, you will have several tests and be interviewed by various team members to determine whether transplantation is the best treatment option for you. The tests may include:

• routine blood work
• x-ray of the heart and lungs
• abdominal ultrasound
• CT scan
• pulmonary function tests
• ECG and echocardiogram.

Specialists from the transplant team-surgeons, hepatologists, pulmonologists, anesthesiologists, cardiologists, psychologists, nurses and social workers-are consulted. You will also receive information that will help you decide whether you want to go ahead with the transplant.

Patients selected for liver transplantation have advanced liver disease for which there is no other medical or surgical therapy.

Waiting for a Transplant

After being approved for transplantation, patients are immediately put on BC Transplant waiting list. The waiting list for a liver can vary from several days to up to two years, depending upon how sick the patient is and the availability of a cadaveric donor. It is therefore important to evaluate patients early in the course of their liver disease and to evaluate as an outpatient rather than waiting until their condition becomes desperate.

All patients on the waiting list are treated equally and evaluated objectively.

While on the waiting list, BC Transplant clinic will see you every three months to evaluate your progress . BC Transplant provides a support network for patients and family members, including regular support groups for those who want to connect with a fellow transplant candidate.

Stress during the waiting period

For many, the waiting period is beginning to be recognized as the most stressful time for patients and family alike. The challenge at this time is being able to maintain hope, while at the same time coming to terms with always being sick

In spite of such challenges, we have faith that you can successfully cope with such difficulties. Individual and group counseling are available if you require additional assistance during any phase of the transplant process. We expect that you will have ups and downs while you wait. Rest assured, we don't view your asking for help as being a sign of weakness. The opposite is true, the team is here to help you through the entire transplant process.

A liver support group meets on a regular basis. Please contact your clinical coordinator for more information.

Receiving a Liver Transplant

When a suitable organ has been found, arrangements are made for you to be admitted to the transplant ward and prepared for surgery. You will need to make your own arrangements to get to the hospital. It is a good idea to have a plan to follow for when the call comes. This plan will include arrangements for children, work, pets, and plants.

Sometimes the donor organ is found to be unsuitable and the transplant is cancelled. This can be very disappointing for everyone involved. This is commonly called a dry run, and occurs about 30% of the time.

If the transplant is cancelled, you will return to the transplant unit and discharged from the hospital. For this reason, tell your family or support person not to leave the hospital, or to stay close by, until they know the transplant is a go.

Transplant Surgery

Liver transplantation is often referred to as orthotopic, because the transplanted liver is put in exactly the same place the liver normally is in. The operation begins by removing the diseased liver. To remove the liver, it must be detached at five sites. Four of these sites are blood vessels, while the fifth site is the common bile duct. The new liver is then reconnected at the same five sites. The operation will take approximately six to ten hours.

The surgery is performed through a large incision in the centre of your abdomen. The incision looks like a "Mercedes" car symbol. Small incisions may also be made in your left armpit and left groin to insert the veno-venous bypass system. This system mechanically pumps blood from the lower part of the body to the heart while the surgeon is implanting your new liver. Please note that the veno-venous bypass may not be necessary for all patients.
More details on the actual surgical procedure are available from your transplant team.

After the Operation

After the operation, you will be taken to the intensive care unit to recover. You will hear voices and the sound of medical equipment around you. For several hours you will be very drowsy. You will notice a large bandage on your abdomen, and various tubes and lines connected to you. You may also have dressings on your left axilla and left groin. These dressings cover incisions that were made to connect you to bypass during surgery.

Recovery

During the first day or two, you will not be able to eat or drink. You will gradually be given liquids, and then solid foods.

While you are in the intensive care unit, you will receive one-to-one nursing-the nurse assigned to you will look after you only. You will be given medications for pain to ensure that you are as comfortable as possible.

The average stay in the intensive care unit is two days.

Living with a Liver Transplant

Anti-rejection drugs
Rejection episodes
Biopsies
Infection
Medication and other costs

You must live in the lower mainland (close to Vancouver and VGH/SPH) for approximately three months following surgery so that you can be closely monitored. When you first leave the hospital, you will need to visit the clinic usually twice a week, and sometimes more frequently depending on the care you require. If you are from out of town, this is a major consideration and should be discussed prior to coming to Vancouver for transplant. For many, this involves both financial and emotional hardship. Discussion with your social worker prior to transplantation is key, and your social worker will work with you to establish a plan.

After six months, your clinic visits decrease to once a month, and eventually, to once every three to four months or less. The frequency of your follow-up visits to the clinic depends on your health and progress. This varies for each individual.

Anti-rejection drugs

Acute rejection is a common complication for transplant recipients. It occurs because your body's immune system recognizes your transplanted organ as "foreign" and tries to get rid of it. This process is called rejection. Your immune system is your body's defense against infection and disease. If nothing were done to stop the immune system, it would eventually damage or destroy your new organ.

Successful organ transplantation is now possible because of the use of anti-rejection drugs. To try to prevent your immune system from rejecting your new organ, you will be given immunosuppression or anti-rejection drugs (these two names are interchangeable). The doses of these drugs are carefully measured and monitored so that they prevent rejection, but still allow your immune system to recognize and fight rejection.

With the use of these drugs, your chance for a successful organ transplant is excellent. You will have to take the anti-rejection medications for as long as you have your transplanted organ.

Various immunosuppressive drugs are used in combination. When you first start taking anti-rejection drugs, the doses will be high. After the initial period (the first three to six months), as the risk of acute rejection decreases, the doses will be lowered. Usually by the end of your first year after transplant you are taking a considerably lower dose than in the initial period.

The most commonly used drugs are cyclosporine or tacrolimus, azathioprine or mycophenolate, and prednisone. Each drug works in a slightly different way and has different side effects. By taking two or three drugs together, you can be on lower doses of each drug to minimize their side effects, while maintaining an effective defense against rejection and infection.

After you are transplanted, the nurses and the pharmacists on the ward will teach you about your medications, how and when to take them. Initially, nurses will give the medications. Gradually, before your discharge, you will have the responsibility for taking them yourself.

It is a good idea to record the daily doses of drugs taken, and to bring this record to each clinic visit. The dosage of the anti-rejection drugs are frequently changed in the early phase post-transplant, and many people find it easier to write down the changes to prevent any misunderstanding or medication error.

Commonly prescribed anti-rejection drugs

Cyclosporine or Neoral Cyclosporine
Tacrolimus (Prograf®)
Azathioprine (also known as Imuran®)
Mycophenolate (also known as CellCept®)
Prednisone

Cyclosporine (also known as Neoral®)

Cyclosporine revolutionized transplantation because it was the first drug found to be consistently effective for preventing rejection. This drug modifies certain white blood cells called lymphocytes, which are involved in rejection.

To be effective, the drug must stay at a certain level in your blood. If the level is too low, your transplanted organ may be rejected. If the level is too high, your kidneys or liver may be damaged. Usually, any damage is reversible once the drug returns to its proper level. The level of cyclosporine is measured frequently with a blood test while you are in the hospital, and after discharge during visits to the clinic.

Cyclosporine is available in soft gelatin capsules. The capsules are available in 25 mg (grey), 50 mg (white), and 100 mg (grey). Each capsule is wrapped in foil, and should be kept in the foil until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Swallow the capsules whole. You may take cyclosporine with any drink except grapefruit juice (as grapefruit juice will alter the absorption of cyclosporine) unless your physician instructs you otherwise. It is very important that you take cyclosporine with the same drink every time.

The most common side effects of cyclosporine are listed below. Remember that everyone responds differently to medications, so you may experience only some of the side effects or none at all.

Possible side effects of cyclosporine:

• high blood pressure, and headaches
• increased risk of infection
• mild hand tremors
• fine hair growth on the upper body
• gum tenderness (to prevent problems with your gums, brush and floss your teeth daily, and visit your dentist regularly)
• sensitivity to hot and cold, flushing
• runny nose
• vivid dreams

If you notice any of these side effects, tell a member of your transplant team. They will assess whether you are suffering from side effects of the drug or something else.

Tacrolimus (also known as Prograf® or FK-506)

Tacrolimus is another anti-rejection drug that acts in much the same way as cyclosporine. Tacrolimus is used in some transplant patients in place of cyclosporine (tacrolimus and cyclosporine should not be taken together). Tacrolimus, like cyclosporine, is used with steroids and azathioprine (Imuran®) or MMF (mycophenolate Mofetil) to prevent or treat rejection of the transplant organ.

Tacrolimus is available in 1 mg and 5 mg capsules. The 1 mg capsules are white and oblong with "1 mg" written on the top. The 5 mg capsules are grayish-red and oblong with "5 mg" written on the top.

Like other medications, tacrolimus may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking tacrolimus on your own.

Possible side effects of tacrolimus (Prograf®):

• headaches
• tremor
• tingling in your hands or feet
• nausea and vomiting
• diarrhea or constipation
• difficulty sleeping
• changes in moods or emotions

Like other anti-rejection medications, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as tacrolimus, for example, may affect the way tacrolimus works for you, so these drugs should not be taken together.

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Azathioprine (also known as Imuran®)

Azathioprine is also used to prevent rejection. The use of Imuran has changed recently, to be incorporated into your transplant medication regime in the 2nd year of your transplanted kidney. Mycophenolate (described in the next paragraph, has been proven to be more effective for the first year). This drug suppresses the production of certain white blood cells, which are active in the process of rejection. The drug also suppresses the production of cells that are important in fighting infection. A complete count of blood cells (by a blood test) is done daily while you are in the hospital, and regularly at the clinic once you are discharged. The dosage of azathioprine is adjusted to keep the blood counts within safe limits.

Azathioprine is very well tolerated and most people are not really aware of any problem while on this medication. However, like any drug, side effects are always possible. The most common side effects of azathioprine are listed below. Remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of azathioprine:

• nausea and vomiting
• loss of appetite
• skin rash
• muscle/joint pain
• infection

If you notice any of these side effects, tell a member of your transplant team. They will make sure the problem is a side effect of the drug, and not a sign of rejection of your transplant, or another medical problem.

Azathioprine is available in both intravenous solution and oral tablet form. It comes in 50 mg tablets, which can be broken for smaller doses.

Mycophenolate (also known as CellCept®)

Mycophenolate is an anti-rejection drug that works in much the same way as azathioprine (Imuran®). Recently, Mycophenolate has been incorporated into the kidney transplant medication regime for use in the first year of your transplanted graft. It has been proven to be very effective in preventing acute rejection during this first year. Some transplant patients take mycophenolate instead of azathioprine. Mycophenolate is used with either cyclosporine or tacrolimus, and steroids to prevent or treat rejection of the transplanted organ.

Mycophenolate is available in blue/brown gelatin capsules with "CellCept 250" printed in black ink on the blue cap and "ROCHE" on the brown body. Each capsule contains 250 mg of mycophenolate mofetil.

It is important to leave the capsules in the blister pack until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Mycophenolate should be taken on an empty stomach. Swallow the capsules whole.

Like other anti-rejection medication, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as mycophenolate, for example, may affect the way mycophenolate works for you, so these drugs should not be taken together.

Like other medications, mycophenolate may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking mycophenolate on your own.

Possible side effects of mycophenolate:

• nausea and vomiting
• diarrhea
• loss of appetite
• weakness
• swelling of legs and hands
• infection
• headaches

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Prednisone

Prednisone is a steroid, similar to one that your body produces normally. It decreases tissue swelling and suppresses rejection. The initial high dose of prednisone is gradually reduced until a low maintenance dose is established. Higher doses of steroids, called "pulse therapy", are used to treat acute rejection.

The most common side effects of prednisone are listed below. Again, remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of Prednisone:

• stomach upset (should always be taken with food)
• weight gain and fluid retention
• bone thinning
• fullness of the face
• acne/rash
• easy bruising
• joint pain
• mood swings
• medication induced diabetes (high blood sugars)
• infection

If you notice any of these side effects, tell a member of the transplant team. The team will make sure the problem is a side effect of the drug, and not a sign of rejection or another medical problem.

Taking Anti-rejection Drugs

It is important to take your medications at the same time each day so that you maintain adequate levels of medication in your blood. To ensure that the drugs work properly, you must take them exactly as prescribed.

If you miss your dose and it is less than half the time before your next dose is due, then take the missed dose. If it is more than half the time to your next dose, then skip the missed dose and wait for your next dose. Do not double your dose.

For example, if you were scheduled to take your medication every 12-hours and you remember to take your medication within 6-hours of the time it was due, then you can take the missed dose. If you have any questions regarding the schedule of your medications or taking missed doses, then make a note of the time and date of the missed dose and inform the transplant team as soon as possible. If you vomit within one hour of taking your medication, repeat the dose.

*Never change the dose of your drugs or stop taking them unless directed by the transplant team.

*Remember to always inform your doctor and dentist of the medications you are taking.

Rejection Episodes

It is likely that at some time you will experience an episode of rejection. It is referred to as an episode of rejection because it is usually a temporary, reversible event. It is most likely to occur in the first six months of having your new organ, but it can happen at any time as long as you have the organ.

Rejection may occur even if you have been taking your medications faithfully. While you may find this thought unsettling, it is a common occurrence. In most cases, with early detection and treatment, the transplant team should have no problem reversing the rejection completely.

The best way to fight rejection is to stop it before it starts, and to recognize it and treat it early. You can work at preventing rejection by taking your medications faithfully. For early detection learn to identify the signs and symptoms of rejection and report them immediately to the transplant clinic nurse.

Signs of Rejection

Early identification and reporting of symptoms are important in successfully treating and reversing rejection. Most rejection episodes are mild. You may not have any symptoms, and may only be aware that rejection is occurring because it was detected by abnormal liver function determined by your blood work. On the other hand, you may also start to feel symptoms of the rejection episode.

To ensure that the rejection is treated quickly, watch out for any of the following warning symptoms:

• malaise or tiredness
• low grade fever
• loss of appetite
• nausea or vomiting
• abdominal pain or tenderness
• dark yellow or orange urine
• clay-coloured stools
• jaundice (yellow colour of the skin and eyes)

If you experience any of these symptoms, report it to your transplant team immediately.

Treatment of Rejection

When rejection is detected, it must be treated immediately. Patients may or may not be admitted to hospital to treat an episode. Treatment usually involves high doses of a steroid, which can be taken either intravenously (through a vein), or by an increase in prednisone tablets taken orally. In most cases, this will reverse the rejection.

If high doses of steroids are not effective, OKT3 is most often given. OKT3 is a medication which blocks the function of the immune cells that are responsible for rejecting the organ. It is given intravenously for up to 10 days. OKT3 can cause severe flu-like symptoms during the initial two or three doses. You will be admitted to hospital for the initial doses and given medication to help minimize the symptoms. If you have any unusual discomfort or symptoms, report them to your doctor or nurse. You may also be switched to tacrolimus.

Chronic Rejection

Most transplant recipients do not experience chronic rejection, a condition that most often occurs over a long period of time. Ongoing chronic rejection slowly damages the transplanted organ.

Unfortunately, unlike acute rejection, it is not possible to reverse the damage, although it sometimes is possible to halt the progression. As with acute rejection, chronic rejection can occur despite taking your medication regularly. You may need to change to a new anti-rejection drug.

Biopsies

Liver biopsies may be necessary to confirm the diagnosis of rejection. A biopsy is usually performed following two elevated liver function tests. In the ultrasound department, you will be given a local anaesthetic. You will remain lying flat in the ultrasound department for one hour following the procedure.

Infection

A possible side effect of anti-rejection drugs is an increase in infections. While suppression of the immune system is necessary to prevent organ rejection, it weakens the body's ability to fight off infections. Fortunately, there are ways of reducing the risk of infection while still maintaining adequate defenses against rejection.

The risk of contracting an infection is higher during the first few months following a transplant when your doses of anti-rejection drugs are high. As the doses fall, the risk of infection falls. As with rejection, the key to fighting an infection is to prevent it, identify it early, and treat it quickly.

Preventing Infection

The best way to prevent an infection is by avoiding close contact with people who may be ill. Most viruses, bacteria, and fungi are passed from person to person in tiny water droplets and may be transferred simply by shaking hands. Someone sneezing or coughing is sending out droplets, which you might breathe in, or transfer to your mouth or other mucous membrane (such as your eyes) with your hands.

During the first few months following your transplant, you must be diligent in avoiding infections. This may mean having to avoid normal close contact with family members or your spouse if they are sick.

You may not be able to prevent all infections, but you can certainly reduce the risk by washing your hands regularly and avoid putting your fingers in your mouth or touching your eyes. Family and friends with infections should also wash their hands before touching you.

Also avoid:

• people with colds or infections
• crowded, poorly ventilated, smoke-filled rooms
• public transportation, especially at rush hours
• public whirlpools
• activities that may cause breaks in the skin (when gardening, for example, wear gloves)
• changing cat and bird litter

It also helps to alert your co-workers to the fact that you are on immunosuppressants. You will find that people are remarkably considerate when they know the situation. After the transplant, you may be taking medications as a preventative measure against commonly occurring infections.

Medication and other costs

The three anti-rejection drugs you will be prescribed are available free of charge from the Transplant Outpatient Pharmacy located in the Transplant Clinic. Other non-immunosuppressive drugs must be purchased by you at your local pharmacy. Keep your receipts so you can apply for reimbursement of a portion of these costs through BC's Pharmacare Plan. Application forms are available from your pharmacy. For more information, talk to your pharmacist.

During the first three to six months, you may also be taking drugs to prevent infections, treat high blood pressure, or help with acid reflux, so the total cost of your medications will be quite high. Once you stop taking some of these drugs, the cost will come down significantly. Talk to your transplant team and other recipients about the best and cheapest places to buy your drugs.

Besides medications, there are other expenses that you may incur after your transplant, including:

• Accommodation in Vancouver before you can return to your community
• travel to and from the Transplant Clinic
• health monitoring equipment and supplies, such as blood pressure device, weight scale, and thermometer
• medic alert bracelet or necklace
• other supplies if required (gauze, tape, cleaning solutions)