Liver Transplantation

Liver Transplantation is the surgical replacement of diseased liver with a healthy liver. Liver transplantation was not an option for patients with end stage liver disease in India until recently. Patients with Liver disease were given only supportive care and almost every one of them died from complications of liver failure. About 1,00,000 patients die from the complications of liver disease each year in India. Brainstem dead donor or Cadaveric Donor Liver Transplantation, the common modality of Liver transplants in the west, is fraught with issues and has still not taken off in India. Living Donor Liver Transplant remains the main modality of Liver Transplantation.

Liver can tolerate injury until about two-thirds of its volume is irreversibly damaged. It constantly fixes the damage done to it and spontaneously regenerates itself. However, when the damage is extensive, patients start to manifest symptoms of liver disease gradually. The common causes of end stage liver disease in India are viral Hepatitis B & C, alcoholic hepatitis, cryptogenic, non alcoholic liver disease, Wilson and Hemochromotosis. The common complications encountered are Ascites, initially responding to medications and later refractory to medicines, Variceal Hemorrhage, Hepatic Encephalopathy and spontaneous bacterial Peritonitis. Other complications are Hepatorenal Syndrome, Hepatic Hydrothorax, Hepatopulmonary Syndrome, Portopulmonary Syndrome, Hepatocellular Carcinoma, Portal Vein Thrombosis etc. Almost all cirrhotic patients will have features of malaise, fatigue and muscle wasting.

Who needs a Transplant?

Anyone with End-Stage Liver Disease from any cause, Fulminant Liver failure, Hepatocellular Carcinoma, metabolic liver disease could be a candidate. They are usually treated by hepatologists who initially try medical management and refer cases to the Transplant Surgeons for evaluation for transplant, at an appropriate time. The patients then undergo complete medical and cardiopulmonary evaluation after which they could be considered as potential recipients. Any condition such as malignancy other than liver cancer, sepsis and infections, irreversible neurological state or terminal non hepatic diseases preclude them from undergoing Liver Transplantation

Steps in Pre-Transplant Evaluation Process

 

• Referral by your physician or Gastroenterologist:
  The physician/ gastroenterologist who is following a patient with
  Liver disease refers him to the Liver Transplant center when the
  patient manifests worsening of Liver disease, complications of
  Cirrhosis, Acute Fulminant Failure or detection of Liver Cancer
  in someone who has cirrhosis
• Evaluation by Transplant Surgeon: Following the referral,
  the patient is completely examined by the surgeon. At this
  point the patient may have known or unknown cause of liver failure.
  The goal of evaluation is to ensure that the patient would be an
  eligible candidate for Liver Transplantation. The surgeon reviews the
  latest Liver function test which gives an idea of surgical risk of the
  patient, may order for tests such as CT tomography of the liver to
  study the anatomy, and rule out the presence of Liver Cancer or
  any difficult situation that could be identified at this stage.
  At this juncture, renal and cardiopulmonary conditions are
  also checked to see if there are any associated risks.
  Any absolute or relative contraindication is looked for.
• Psychosocial interview: The transplant team besides the surgeon
  also interviews the patient and the family to ensure that they have
  understood the concept, have a reasonable expectation with respect
  to the outcome and compliance of the potential recipient. Extensive
  discussion is held with the patient and the family members on
  post-operative issues, complications and instructions on short and
  long term follow-up.
• Donor Evaluation: If there is a family member who is interested in
  living donation, simultaneous donor work- up is carried out after
  extensive discussion with the donor, explaining the risks and benefits.
  The donor undergoes clinical examination, blood tests, CT scan of the
  Liver to assess liver volume, and further relevant tests. Patients who
  do not have living donor options will be placed on the waiting list
  for cadaver organ transplant. The transplant team follows the patient
  regularly. The waiting time on the cadaver organ transplant list is
  unpredictable as the cadaver organ donation process is inconsistent.

Transplant Surgery

There are two types of Transplant Surgery, namely:

• Cadaveric Donor Liver Transplant
• Living Donor Liver Transplant

Cadaveric Donor Liver Transplant

The waiting time is anywhere between one month and 16 months, depending upon the blood group of the recipient. While waiting for a donor, it is suggested that the family leaves behind two or three contact numbers where they can be reached or other contact numbers if they plan to travel, so that the transplant team can contact them at all possible times. When there is a suitable donor available to match the blood group and other parameters the transplant team contacts the patient's family. This call could be at any time of the day or night, and once called the patient's family should reach the hospital at the earliest. Due to the numerous patients on the waiting list, any delay in reaching the hospital or inability to reach the family could result in the next eligible recipient getting the call. Once the patient reaches the hospital and the admission process is completed, he is subjected to blood tests and examinations by the physician to ensure that he is fit to undergo transplant operation. There is always a possibility that he may not have surgery due to various reasons.

Living Donor Liver Transplant

Due to the lack of Cadaveric Donors in our country, Living Donor Liver Transplants are conducted. The donor and the recipient are admitted to the hospital a day before the surgery. Following admission, series of tests are done. The donor is taken to the surgery suite early in the morning, undergoes surgery where a portion of the donor's liver is removed and implanted into the recipient. The native liver is removed and the new liver is implanted with delicate connections made between native and recipient blood vessels and the biliary system.

Surgery takes 6-10 hours, and following the operation, the recipient will be taken to the intensive care unit. The recipient stay connected to the breathing tube for 24-48 hours, usually depending on his pre-existing illness. After 3-10 days in the ICU, the recipient will probably stay in the hospital for 3-4 weeks in the transplant unit before he is discharged, during when he is advised about his medications and given post-transplant instructions. After a few weeks of rest, the patient normally feels better and is almost back to normal. However, since he is functioning with a new liver, he is required to take medications to prevent rejection of the new liver by his immune system throughout his life.

The initial 6 months are the most critical, when the new liver takes time to adapt to the host body. Following this period, the medication dosage will be decreased gradually although not discontinued completely. During this time the patients will be followed closely with frequent blood investigations and clinic visits.

Transplant Medications

Anti-Rejection Medication

Cyclosporin ( neural/sandimmune) prevents activation of T-lymphocytes, which will attack the new liver. It is given in combination with other anti-rejection medications. The blood level of this medication needs to be checked so that the dosage can be adjusted. Noted side effects include high blood pressure, high blood sugar, kidney function dysfunction, thickening of gums and tremors.

Tacrolimus (prograf) acts similar to Cyclosporin but is more potent. It is taken with other medicines and the blood level of this medication can be checked. The side effect profile is also similar to cyclosporine.

Sirolimus ( Rapammune) inhibits T and B lymphocytes through a totally different mechanism as compared to other medicines. It is taken once a day and the concentration of Sirolimus in the blood can be checked. Noted side effects are diarrhea, nausea, low white cell count, mild renal dysfunction, mouth ulcers and dyslipidemia

Mycophenolate mofettil ( cellcept, myfortic) inhibits lymphocyte proliferation. It is taken twice a day and its concentration in the blood also can be checked and monitored. It is a secondary drug given with Cyclosporine or Tacrolimus. Common side effects are nausea, vomiting, diarrhea and drop in white cell count.

Daclizumab ( Zenapax) or basiliximab ( simulect) is a special antibody infusion that acts on receptor antigens conducting information, to cause proliferation of cells. It is given in one or two doses to initiate immunosuppression immediately after the transplant procedure to prevent rejection.

Anti- infection medication

Oral Anti bacterial, Anti-viral and Anti-fungal medications are given for a longer period of time as a preventive measure against infections. It is usually given for the first few months after transplantation and stopped thereafter.

Other medications

Drugs to control Blood Pressure, Diabetes and High cholesterol are started according to the clinical indication. It is for this reason that close follow-up is required in the initial period post transplantation.

Risks of Transplantation

As with any other surgical procedure, complications may arise after liver transplantation.

Bleeding - There is a risk of bleeding at the anastomosis, the place where the blood vessels from donor and recipient were sewn together. This is minimized by monitoring clotting factors in the blood after surgery and measuring output from the drains placed during the operation.

Hepatic Artery Thrombosis - If a clot forms in the hepatic artery it can cause the liver to malfunction. Abdominal ultrasound is done on the day after the surgery to look for this condition and the patient is monitored throughout his postoperative recovery. If a clot is found, medications or surgical repair can minimize permanent damage and avoid the need for re-transplantation.

Bile Duct Leaks - The ducts that drain from the new liver are attached to a bile duct or portion of intestine in the recipient. This connection can leak and bile can drain into the abdominal cavity, causing infection. If a bile leak occurs, a catheter may be inserted into the abdomen to allow external drainage. This is temporary and can usually be managed without surgery.

Rejection - The recipient's body will recognize the new liver as a foreign invader and develop immune cells, called lymphocytes, to attack it. This is called rejection, and many recipients will experience some degree of rejection after transplantation. Usually, it is easily reversed with medications. The first rejection commonly occurs within three months after the operation. The patient is monitored closely during this time so the warning signs of rejection can be spotted early and steps can be taken immediately to control it. A biopsy of the liver is usually necessary to diagnose the extent of the rejection taking place, and to rule out any other problems. Biopsy results will help determine which anti-rejection therapy is best for the patient.

Infection - Because the recipient's immune system is suppressed by medications after transplantation, he is at higher risk for developing certain infections. Medications are hence prescribed to prevent the more common post-transplant infections. The patient needs to routinely monitor his temperature at home and make certain adjustments in his daily living to avoid contracting harmful infections.

Hepatitis Recurrence - If the patient has suffered from Hepatitis B or C prior to receiving his new liver, it is possible to experience a recurrence of the virus after transplantation. To help identify and control any recurrence, he is screened with blood tests and liver biopsies at regular intervals. If recurrence is detected, appropriate medication will be prescribed.

Results of Liver transplantation

Statistics show that the chances for survival for patients who have undergone liver transplantation for one year are 90% and chances for five year survival for these patients are 80%. Without liver transplantation, the chances of survival for patients with end stage liver disease for one year, are approximately 25%.

Pediatric transplantation

Children have a different spectrum of liver disease causing end stage liver disease. Although most of the symptoms and signs of liver disease are the same as that of adults, growth retardation, failure to thrive and developmental defects stand out distinctly. Because of the deficiency of essential elements and poor absorption of nutrients, growth and development is severely stunted. The most common cause of pediatric liver disease requiring liver transplant is Cholestatic liver disease such as Biliary Atresia followed by metabolic disorders and Acute Fulminant Failure.

Children are evaluated in the same fashion as adults. Cardiac testing is done to rule out congenital cardiac anomalies. Parents are interviewed to assess the overall status of the family. Young children are easily served by Living donor liver transplants, where the donor, usually the parent, donates less than one- third of their liver volume. The liver grows back to its normal size in the donor and assumes the required size within the child, and then continues to grow with the overall growth of the child in the future. The survival rates of the child after transplant are extremely good, and most of the children make good the growth deficiency after successful liver transplantation. Once they successfully complete the first few months after liver transplantation, they are almost like other normal children, except that their parents have to pay attention to their drug regimen.

Life Post Donation

Potential liver donors related to the recipient are carefully evaluated to select those individuals who can safely donate a portion of their liver, which can function immediately within the recipient's body. General criteria for liver donation include being in good general health with no medical problems, aged between 18 years to 50 years, having a blood type compatible with the recipient's and having an altruistic motivation for donating.

A living-donor candidate must complete the following evaluation process to determine if they can safely donate a portion of their liver:

• The first testing determines if the donor's blood type is compatible
  with that of the recipient. Additional blood tests are performed to test
  for healthy functioning of the donor's liver, kidneys and thyroid, and to
  screen for exposure to transmittable viruses such as hepatitis
  and HIV.
• If donor and recipient blood types are compatible,
  a physical examination with a physician is scheduled to further
  assess the donor's overall heath.
• Abdominal ultrasound testing is performed to screen for
  abnormalities of the liver and other abdominal organs and
  blood vessels.
• Magnetic Resonance Imaging (MRI) is performed to create detailed
  anatomical "road map" of the donor's internal organs to
  aid the surgery.
• Sometimes additional testing, such as pulmonary function testing,
  echocardiogram, or exercise stress testing is required.

The standard time required to complete the donor evaluation process is two to four days. If necessary, however, it can be completed in as little as 24 hours. Typically, a donor remains in the hospital for four to seven days after surgery. Donors spend their first night after surgery in the Surgical Intensive Care Unit for close monitoring by specialized nursing staff. The following day, they are usually transferred to the general surgical floor, where the nurses are specifically experienced in caring for liver donors.

Donors are encouraged to get out of bed and sit in a chair the day following surgery, and to walk the corridors as soon as they are able to do so. To make the donor's immediate recovery as comfortable as possible, Patient-Controlled Anesthesia (PCA) is used, which enables self-administration of pain medication following surgery.

Every donor's recovery time is different but, typically, donors spend four weeks recuperating after surgery. In the month following discharge from the hospital, donors return weekly to OPD for outpatient monitoring. Individual recovery rate and the type of occupation dictate how soon a donor can return to work, but it commonly averages three to six weeks.

Donor safety and their quality of life will be the main concern of donor surgery. Careful precautions are taken at the time of surgery and immediately following surgery. The donor can start eating within 2 or 3 days after surgery and there are no diet restrictions after surgery. Following discharge from the hospital in about 7 -10 days after surgery, the donor can resume normal lifestyle such as eating, walking, taking showers and climbing the stairs at home. We strongly advise them not to lift heavy objects more than 2.5 kgs for up to 4 weeks from the time of surgery. This is a precaution to prevent incisional hernia after surgery. For up to 3- 6 months, some donors may feel mild numbness or tingling at the incision site which recedes eventually. Pain medicines may be required during the initial post-operative period. Otherwise the donors need not be on any medicines after donation surgery. The liver grows back and there are no long term consequences.

Living with a Transplant

• Diet

Before Transplant

Cirrhotic patients should avoid food with high protein content such as red meat, high pulses content or commercial protein supplements. The increased load of protein presented to the liver worsens the hepatic encephalopathy. The recommendation is to take 60gram protein diet. Other dietary recommendations include:

• Avoiding fried food
• Having a diet which is well balanced in carbhohydrates and fat
• Decreasing sugar intake
• Restricting fluid intake

After Transplant

After transplantation, the recipient should receive adequate hydration, of up to 1.5-2 liters of fluids per day. The following dietary considerations should be followed:

• Include lots of fruits and vegetables in the daily diet
• Eat whole grain cereals
• Use low fat milk
• Only eat lean meat
• Avoid high sugary food, sugary snacks
• Follow a low salt diet
• Lifestyle

Before Transplant

Patients should continue to be as active as possible. While they need not develop muscles, they can continue to walk daily, and perform movements and activities that will prevent loss of muscle tone throughout the body. They are advised to avoid contact sports due to the tendency to bleed.

The patient should strictly abstain from alcohol and check with the physician before he starts any new medicines. Self medication should be refrained from and regular follow-ups with the physician and blood tests need to be conducted as per physician's recommendation.

After Transplant

The patient is advised to resume regular exercise and other activities after 4 weeks of the transplant operation. He needs to monitor his weight frequently and conduct blood tests and follow-ups with the physician as per instructions. This apart, he can participate in normal social activities with friends and family.

Recent Trends

Liver Dialysis: In patients with Fulminant Liver failure, support with artificial liver for a few days will allow the native liver to regenerate and restore back to normalcy. The liver support system is able to perform the detoxification that is normally done by the liver to prevent irreversible neurological damage and swelling. The synthetic function of the liver can be handled by exogenous administration of proteins and coagulation factors.

Stem cell transplantation: Stem cell transplantation either in the form of autogenous peripheral stem cell or embryonic or umbilical cord blood stem cell can develop into normal hepatocytes so that normal function of the liver can be restored

Hepatocyte transplantation: This method refers to the transplantation of only the liver cells or hepatocytes instead of transplanting the entire organ. This is fruitful in the case of recipients who lack certain enzymes normally present in the hepatocytes.

Internet links

unos.org, ustransplant.org, baylortansplant.com,uktransplantregistry