Assessment for Liver Transplant
Is liver transplantation a treatment of last resort, when everything else has failed?
Well, yes and no. Medical treatment is likely to allow a patient’s prolonged survival with good quality of life, and then transplantation would be reserved for the future. However, ideally we like to undertake liver transplant surgery before the patient’s disease is at the terminal stage when he or she is too ill to withstand major surgery and will not survive until a suitable donor liver is available. Liver transplant should not be considered as a treatment of last resort, because with more advanced and serious disease, the outcome of liver transplant would also get affected adversely. The patient should opt for transplant when his or her disease is still in control and has not developed the complications of cirrhosis as the results of liver transplant in ‘compensated’ cirrhosis are better than when a patient has developed complications and ‘decompensated’ cirrhosis.

How is the decision made to transplant a patient’s liver?
The decision to transplant a patient’s liver is made in consultation with all individuals involved in the patient’s care, including the patient, referring physician, and the patient’s family. The patient and family’s input is vital in this decision-making process; they must clearly understand the risks involved in proceeding to transplantation and the post transplant care. In general, this means that a person has a poor chance of living in the next 1-2 years from their underlying liver disease.

What is the process of assessment for liver transplant? 
Referral for Transplant Ideally, patients with cirrhosis should be referred to the liver transplant unit when they develop evidence of deteriorating liver function, experience their first major complication e.g. ascites, variceal bleeding, spontaneous bacterial peritonitis (an infection that can develop in the abdominal fluid), encephalopathy or malnutrition. Patients with hepatocellular cancer (primary liver cancer) and cirrhosis should be referred for assessment by the liver transplant team as soon as the tumor is discovered, so that optimal treatment can be decided.

Transplant Assessment
A detailed assessment is carried out prior to deciding whether a patient is a candidate for liver transplantation. As a general rule there are four basic requirements, which would indicate that you might be considered suitable for assessment:
a. Irreversible, progressive liver disease
b. The liver disease fails to respond to all other forms of medical and surgical treatment
c. Absence of other major diseases
d. Ability to understand the nature and risks of liver transplantation

The assessment process
There are a number of tests that will need to be performed while you are undergoing assessment for transplantation. The results of these tests provide an overall assessment of your current state of health and help determine if transplantation is the right option for you. There are a number of baseline tests that all patients need to undergo; extra tests are tailored to the individual situation. In most people, these tests are performed on an outpatient basis. Time: usually 2 – 3 weeks needed to complete tests in an urgent setting these tests can be completed within a day.

An outline of the tests you will need to undergoBlood tests
A number of tests including:
• Biochemistry
• Hematology
• Blood clotting profile
• Cross-matching
• Hormone levels
• Hepatitis screening
• Screening for exposure to certain viruses, which will help to optimize your post
Transplant management
• A 24-hour urine collection to assess kidney function

Other tests include:
• Chest X-ray, hip X-ray, spine X-ray
• ECG and cardiac ECHO
• Lung function tests
• Abdominal CT scan (This computerized image will show the size and shape of the liver and major blood vessels. At times, this test reveals previously unsuspected liver tumor.)
• Endoscopy
• Female patients must have a Mammogram and Pap smear
• Dental check
Other tests as individually indicatedHowever the donor organ has to be matched with you with regard to blood group and size.

What else happens? 
During the course of the assessment you will have the opportunity to meet one of our dietitians who will advise you about your particular dietary requirements. You will also be able to meet with transplant coordinator, who can advise and help you with any specific issues you may need assistance with in relation to family, and also to guide you about the paper work required for clearance for transplantYour doctor will also decide whether you would benefit from a consultation with our psychiatrist or clinical psychologist.

Depending on the results obtained from these tests, and the complexity of your case, further tests may be arranged as necessary in order to establish suitability. You may also need to be seen by other specialists, such as a lung specialist or heart specialist. Following review of your tests by your liver specialist, an appointment will then be arranged for you with one of our Transplant Surgeons and our Transplant Anesthetist.

Following AssessmentAfter you have gone through all these various stages, the decision whether to proceed to transplantation is discussed with you and your family. At this time, possible outcomes include:

a. You are considered suitable for transplant and the severity of your liver disease warrants your name being placed on the active waiting list.
b. You are considered as suitable for transplant, but deferred for an indefinite period because you are too well. This may be months, years or never. You return home and remain under the care of your specialist if appropriate, who remains in contact with the specialists at Apollo Liver Transplant, Hepatobiliary and Pancreatic Surgery Unit.
c. There is the possibility you are unsuitable for transplant for whatever reason. The main reason may be that the risks of transplant

Where do the livers that are donated for liver transplantation surgery come from?
Deceased donor liver transplant (DDLT)Livers are donated, with the consent of the next of kin, from individuals who have had brain death. Brain death is usually the result of a head injury or a brain hemorrhage. When such a donor is identified, a network of skilled professionals connected by computers contact the transplant centers and makes arrangements to retrieve whatever organs may be donated. Another way is Donation after Cardiac Death in which the donation is carried out once the heart stops beating. Frequently, this involves a team of skilled professionals from transplant centers flying to the donor hospital to remove the organs.Another method is Living Donor Liver Transplantation (LDLT) in which a near relative of the patient comes forward to donate his or her partial liver.

How can individuals donate their organs?
If you wish to be an organ donor, carry an organ donor card and more importantly discuss organ donation with family members since they will have to give consent for the donation. Liver transplanted from a deceased donor is known as cadaveric transplant. The majority of livers that are transplanted come from brain dead organ donors where consent is available. A liver transplant from a brain dead donor (cadaver) needs to occur within 12 to 24 hours after the liver is removed from the donor for the organ to remain viable. During this time, the surgeon will do a final assessment of the donor liver to ensure it’s healthy and a good match.
Due to personal, religious, unawareness, many people do not come forward to be an organ donor. This causes shortage of liver for transplantation and many have died waiting for a compatible liver.

Who can be a live donor?
Any individual who is a first or second degree relative of the recipient, who is an adult and is less than 50 years of age, and is free from any medical illnesses can become a live organ donor for a partial liver graft.

Do the patient who is donating the liver/donor and the patient who will receive the liver/recipient have to be matched by tissue type/sex/age etc.?
For liver transplant only blood group matching is requires. Tissue typing is not really required in this procedure. Both ABO compatible and incompatible liver transplants can be carried out successfully.

What are the major risks in liver transplantation?
Before liver transplantation, risks to the patient are mainly those who develop acute liver failure and it’s complications of bleeding, coma, kidney failure or progressive complications of chronic liver failure that might render the patient an unacceptable risk for surgery. This can also include intestinal bleeding, severe abdominal fluid accumulation, confusion as well as coma and severe infections. With surgery, the risks are those that are common to all forms of major surgery, or involve technical difficulties in removing the diseased liver, involve implanting the donor liver, and/or involve consequences of being without liver function briefly. Immediately after the operation, risks include bleeding, poor function of the grafted liver, bile leaks, and infections. We monitor the patient carefully for several weeks after surgery for signs that the patient is rejecting the new liver as well. Rejection long-term becomes less and less common.

patient may continue on a low dose of tacrolimus only life long. Newer drugs are consistently coming into the market and these drugs regimens may change depending upon the latest drug information’s available. Organ rejection is a constant threat and requires a careful monitoring to detect if organ rejection is starting. So, it’s likely that your transplant team will make adjustments to your anti-rejection drug regimen.
After your transplant, it’s extremely important that:

• • Keep all your doctor appointments
  • Undergo every recommended lab test
  • Take all your prescription drugs It’s also important to find a good pharmacist who can help you
  • Understand your medications
  • Manage your medication schedule

Although rejection is a scary word, it doesn’t necessarily mean that you will lose your new organ. Most of the time, a rejection can be reversed if your doctor detects its early signs. The symptoms of rejection would vary if you have undergone a liver transplant alone and if you have had a combined liver and kidney transplant. So, it’s important to familiarize yourself with the early symptoms of rejection that are specific to your transplant. If your doctor identifies a rejection, he or she will first try to reverse it by adjusting your medications. For example, you may need to:

Switch to a new drug
Add another drug
Take a larger or smaller dose of your medicationsWe will help you develop good health habits to keep your body as healthy as possible. We will urge you to:Keep all wellness checkups
Monitor your blood pressure, weight, and cholesterol
Get all recommended health screenings on schedule

What side effects do patients who have had liver transplantation commonly experience from the medicines they take to treat or prevent rejection?
Life-long immunosuppression is necessary and tablets must be taken daily. Currently, most patients take tacrolimus or cyclosporine twice daily, with the dose being decided on the basis of blood test levels taken just before the morning dose is due. Along  with this a second drug mycophenolate mofetil or azathioprine is taken twice a day. Prednisone is continued as the third drug for a period of approximately 3- 4 months, but in patients with autoimmune diseases it is continued for a longer rime. All drugs as an outpatient are taken orally (by mouth).

Side effects

Any form of long-term immunosuppression brings with it an increased risk from infection. The risk is highest during high-dose prednisone therapy, so during such times patients need to be isolated from anyone suffering from an infection. Other risks include the development of diabetes, high blood pressure, high cholesterol and kidney damage. Reducing or changing the immunosuppressive drugs or using additional medications can manage most of these complications. In the long-term, there is also a slightly increased risk of malignancy in patients taking immunosuppressive drugs. These risks have to be balanced against the necessity to take the drugs that prevent the body from rejecting the liver.     There are three main drugs used for liver transplant patients. There are other drugs as well, which may be required under special circumstance. The common drugs used and there side effects are listed below:

Tacrolimus (FK506) and Cyclosporine
Stops special white cells (T cells) from becoming active in your blood and attacking your transplanted liver. Either Tacrolimus or cyclosporine is used. Tacrolimus and cyclosporine are similar drugs and work in a similar way but have some different side effects. These  drugs are the main stay of postoperative immunosuppression. Doses are adjusted according to blood levels. They are never used together because of their shared toxicities.

Side effects of Tacrolimus include:
i) Impaired kidney function (picked up on routine blood tests).
ii) Increase in blood pressure
iii) Neurological side effects that include headaches, mild tremors, insomnia, possible nightmares. Rarely patients may experience severe side effects including confusion, seizures and coma. These side effects can be effectively controlled with
dose adjustments
iv) Increased blood sugar levels or diabetes
v) Increased risk of infection
vi) Raised potassium level
vii) Nausea and vomiting
viii) Mild hair loss

Cyclosporine (Neoral)
Again Cyclosporine is a strong immunosuppressive drug that stops special white cells (T-cells) from becoming active in your blood and attacking your transplanted liver that normally fight against transplanted tissue introduced into your body. It is almost always given along with prednisone.

Side effects of Cyclosporine include:
i) Impaired kidney function (picked up on routine blood tests).
ii) High blood pressure.
iii) Hot flushes or sweating.
iv) Numbness or tingling in the hands, feet or mouth.
v) Shaking or trembling hands and feet, but this decreases with the reduction in dose over time.
vi) Hair growth, most commonly noted on the face, arms and legs but this decreases with reduction in dose over time.
vii) Overgrowth of gums sometimes associated with soreness, swelling and redness, hence the need for regular mouth cares.
viii) Sinus drainage, “runny” or “stuffy” nose.
ix) Increased risk of infection.

How to take your Tacrolimus or Cyclosporine
i) Tacrolimus/cyclosporine is given in two divided doses 12 hours apart usually taken at 9 am and 9 pm.
ii) It is very important to take tacrolimus/cyclosporine regularly exactly as prescribed. You must not alter the dose or time taken without medical advice.DO NOT RUN OUT OF CAPSULES.iii) Tacrolimus/cyclosporine is usually dispensed initially through the hospital pharmacy and later can be bought from pharmacies through prescription
iv) Do not take your Tacrolimus or Cyclosporine prior to having your blood taken on the morning of your visit. Bring your morning dose of medication with you and take as soon as possible after the test. Some people taking Cyclosporine will be asked to have their blood tests exactly 2 hours after taking the morning dose (C2 Level).

Once Daily Tacrolimus
Some patients on stable doses of twice daily tacrolimus may be switched to a once daily-prolonged release formulation. This should be taken at least 1 hour before breakfast or 2-3 hours after breakfast. It is much easier to remember to take a capsule once a day! Blood tests to monitor the level are taken just prior to taking the next dose.Prednisone is a steroid hormone similar to cortisol, which your body produces normally. It reduces the number of circulating white cells in the blood by dampening down the inflammatory response. The dose given is initially high post transplant and is gradually tapered down until you are on fairly small dose. It is given in conjunction with other drugs to prevent rejection.

Side effects include:
i) Stomach irritation that may occasionally cause stomach ulcers. Never take prednisone on an empty stomach so you should take it after breakfast each day.
ii) Fluid retention, high blood pressure and swelling of the face, hands or ankles.
iii) Weight gain due to an increase in your appetite and subsequent increase in food intake.
iv) Increased risk of infection, especially in the first few months after transplantation while your prednisone dose is high.
v) High blood sugar (diabetes) may occur with high doses of prednisone therapy. This is called “steroid-induced” diabetes. If you are a diabetic, you may require additional insulin to maintain a normal blood sugar. You will be instructed in a diet that will help you control this side effect if necessary.
vi) Skin changes such as acne, rashes or bruising.
vii) Mood changes that may swing from feeling “up” to feeling “down”.
viii) Softening of the bones (osteoporosis) can be experienced after long-term use of steroids. A diet high in calcium or supplementation with calcium and vitamin D capsules will help, and the prednisone dose is reduced as soon as possible after transplant NEVER STOP OR REDUCE PREDNISONE WITHOUT MEDICAL ADVICEMycophenolate mofetil
One of the newer immunosuppressant medications similar to azathioprine that is part of the three main immunosuppressant’s given to patient post transplant. It is taken twice a day 12 hours apart.Side – effects include:
i) Vomiting
ii) Diarrhea
iii) Low white cell count

Azathioprine (Imuran)
Azathioprine is used for the suppression of your immune response. It acts on the bone marrow by decreasing the number of white blood cells, which fight infection. With azathioprine there is an increased risk of infection and an increased tendency for skin cancers. This drug is usually not used now a days as a regular immunosuppressant in liver transplant, but is reserved as a 2nd line drug if the patient is developing side effects from mycophenolate mofetil.

Side effects include:
i) Bone marrow depression – a low white cell count is the most common problem, but a low platelet count and anemia may occur.
ii) Nausea or vomiting – so take your Imuran after meals to lessen stomach upset.
iii) Occasionally, people are allergic to azathioprine, and are unable to take it.Sirolimus/Rapamycin or Everolimus
These belong to a newer generation of immunosuppressant drugs. They act by stopping special white cells (T cells) from becoming active in your blood and attacking your transplanted liver. They have a different side effect profile from tacrolimus/cyclosporine. They are taken once a day and the dose given is dependent on the level of the drug in your blood.Side – effects include:
(i) Hyperlipidemia (high cholesterol levels in the blood)
(ii) Abdominal pain and diarrhea
(iii) Low red blood cell count (anemia)
(iii) Low white blood cell count
(iv) Low platelet count (thrombocytopenia)
(v) Acne and rash

Other Drugs used after Transplantation Valganciclovir 
Ganciclovir is used for the prevention and treatment of CMV (cytomegalovirus) viral infection. This is a viral infection transplanted patients may be prone to because of their suppressed immune systems and usually reactivates from prior infection in the recipient. It is given as capsules if and when required after transplantation. Some patients may still develop CMV once Ganciclovir tablets are stopped and this will require treatment with either intravenous (through a vein) Ganciclovir or oral (by mouth) Valganciclovir.

Septran
One Septran tablet is given three times a week to all patients after transplant to prevent a type of chest infection called Pneumocystis carinii (PCP) which immunosuppressed patients may be prone to. This medication is continued for 3 months.

Fluconazole
Fluconazole is a medication used for treatment and prevention of yeast infections. An example of a yeast infection is thrush- white patches on the tongue and oral cavity. It is usually stopped 1-2 months after transplant.Antihypertensives
Antihypertensives are drugs used to treat high blood pressure. Patients taking Cyclosporine or Tacrolimus often get an increase in their blood pressure. If this occurs, a variety of medications can be used.Listed below are other medications that may be required after a transplant:
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Insulin
Insulin may be required for patients who have high blood sugar levels after transplant. Oral diabetes medications. Some patients develop only mild diabetes that can be managed with tablets such as Gliclazide or Metformin.Acid-lowering medications (proton-pump inhibitors)
Rabeprazole, pantoprazole, esomeprazole and similar drugs are used to prevent the development of stomach ulcers that can be caused by stress and/or prednisone.

DRUG INTERACTIONS
Many drugs have the potential to interact with your transplant medications. Please check with your doctor about the possibility of any drug interactions with your transplant medications before commencing any new medication.Drugs that may increase blood levels of tacrolimus/cyclosporine include macrolide antibiotics such as erythromycin or roxithromycin (Rulide), antifungal medications such as fluconazole, certain blood pressure medication (calcium channel blockers), and grapefruit juice.Levels may be lowered by other medications, including rifampicin, St John’s Wort, and antiepileptic’s.Over-the-counter drugs
Check with your physician before you take ANY over-the-counter medications, such as cold or cough medications. These medications may mask a serious infection that must be investigated by your doctor. Unless specifically ordered by your physician does not take aspirin or anti-inflammatory drugs such as ibuprofen as they may cause stomach irritation and kidney impairment.Compliance: a crucial factor
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When you, as a patient, are said to be “compliant”, it simply means that you are, to the best of your ability, following the instructions of the doctors, nurses, and other professionals responsible for your care. Specific examples of compliance include:
• Not missing any of your follow-up visits and laboratory tests
• Exercising regularly and maintaining your weight
• Learning all you can about the long-term care of your transplant

However, for transplant recipients the most important aspect of compliance is taking your medication exactly as the transplant team instructed you – without missing a single dose –even if you feel fine. For as long as you have a transplant, you will have to take immunosuppressive drugs. Not taking your immunosuppressive medication at the right time and in the correct amount is one of the most common reasons for rejection and transplant failure.

Are patients who have received a transplanted liver more susceptible to other infections?
The patients undergoing liver transplant are on immunosuppressive medications to avoid rejection of the organ. But this predisposes them to acquire infections, which may not occur in a person who is not taking immunosuppressive medications. The patients therefore have to alter their life styles a bit to circumvent this problem of being susceptible to infections. They are taught proper sanitization techniques and to be cautious to avoid eating raw vegetables and fruits, and to eat properly cooked food. Precautions regarding meeting people, eating habits and to contact the medical team in case of any infectious episodes. Infections however minor they may appear cannot be ignored post liver transplant and following consultation with the transplant team, proper medications needs to be taken.

How safe is a liver transplant and what is the life expectancy?
Liver Transplant is a major surgical procedure with a lot of factors determining its outcome. The outcome is very dependent on the preoperative condition of the patient, intra operative technical factors and postoperative recovery. Over all in living donor liver transplant one expects a more than 90 percent success rate in the postoperative period. Preoperative factors such as underlying kidney dysfunction, cardiac issues, recurrent infection in the abdominal fluid, mental obtundation (hepatic encephalopathy) and confusion stage (hepatic encephalopathy), recurrent hospital admissions and poor nutritional status all can have significant impact on post operative recovery. Hence the better the patient is optimized before surgery, better is the outcome. With increasing experience intra operative technical errors have drastically come down. In the post operative period major factors determining the outcome are the kidney functional improvement, infections (as the immunity is low) and organ rejection.

Can I go back to work and productive life after liver transplant?
Patients who recover well following liver transplant go back to leading a productive and active life. There is a major shift in life from being revolving around the hospital in the preoperative period to leading a physically, sexually and mentally active life while being on a regular follow-up at the hospital.

Can individuals have physical activity after receiving a new liver? Sexual activity?
The energy levels of the body improve if the post transplant course has been uneventful. The patient’s ability to do physical labor improves and gets vigor back in life. Most people may return to work, school or normal activities within 2 to 3 months after the operation. It is often helpful to return on a part-time basis and increase the hours slowly as the energy levels rise. Most patients can resume driving within 4-6 weeks after transplant but this depends on the general health of the patient.Most people can have a normal sex life after a liver transplant. A usual wait of 6-8 weeks before resuming sexual activity is recommended because there may be stress on the abdominal muscles. These patients are at a higher risk of Sexually Transmitted Diseases and are advised a monogamous relationship, use of latex condoms and other precautions. It is recommended that women avoid pregnancy the first year after a transplant. Birth control barrier methods using latex condoms with spermicidal jelly or cream are recommended. Birth control pills or other hormonal methods of contraception need to be discussed with the transplant team as these may damage the liver.Travelling should be undertaken at least 6-12 months after the operation especially if it is somewhere remote. Vaccinations, medications etc. are important before considering a vacation. The patient is always advised to carry all the medical info in form of electronic file so that the medical history is available to the treating doctor in any remote area should the need arise in an emergency

From the description, patients with successful liver transplants seem very healthy. How long cans this goohealth last?
There is every indication that those who are well one year after a liver transplant have an excellent chance at long-term survival. If patients are on regular wellness check ups and in consultation with the transplant team, then excellent 5 year, 10 year and more results have been obtained. Beyond 5 years post transplant, death may occur due to reasons other than the liver as in general population. Heart disease and cancer are the most common diseases that can result in death after transplant besides recurrent disease. Patients should not smoke or drink alcohol after liver transplantation.