Liver disease is a common and serious problem in our country. It is important for liver transplant candidates and their families to understand the basic process involved with liver transplants, to appreciate some of the challenges and complications that face liver transplant recipients (people who receive livers), and to recognize symptoms that should alert recipients to seek medical help.

What is liver transplantation?

Liver transplantation is surgery that is performed to remove a diseased liver in order to replace it with a healthy one. Such surgeries have been done for over 38 years. Several people who have had liver transplants go on to lead perfectly normal lives.

When does one require a liver transplant?

Liver disease severe enough to require a liver transplant can come from many causes. In adults, the most common reason for liver transplantation is cirrhosis. Cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury. Scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver. Cirrhosis can be caused by viruses such as hepatitis B and C, alcohol, autoimmune liver diseases, buildup of fat in the liver, and hereditary liver diseases. Many people who develop cirrhosis of the liver due to excessive use of alcohol also need a liver transplant. Abstinence from alcohol and treatment of complications for 6 months will usually allow some of them to improve significantly and these patients may survive for prolonged periods without a transplant. For patients with advanced liver disease, where prolonged abstinence and medical treatment fails to restore health, liver transplantation is the treatment.

In children, the most common reason for liver transplantation is biliary atresia. Biliary atresia is a rare condition in newborn infants in which the common bile duct between the liver and the small intestine is blocked or absent. Bile ducts, which are tubes that carry bile out of the liver, are missing or damaged in this disease, and obstructed bile causes cirrhosis. Bile helps digest food. If unrecognised, the condition leads to liver failure. The cause of the condition is unknown. The only effective treatments are certain surgeries, or liver transplantation.

Other reasons for transplantation are liver cancer, benign liver tumors, and hereditary diseases. Primary liver cancers develop at a significantly higher rate in cirrhotic livers as compared to normal livers, particularly in patients having liver disease secondary to Hepatitis B. Liver Transplantation at an early stage of liver cancer may result in long-term survival for select patients. However, cancers of the liver that begin somewhere else in the body and spread to the liver are not curable with a liver transplant. Sometimes the cause of liver disease is not known. Liver transplants can thus help both adults and children.

How are candidates for liver transplant determined?

Evaluations by specialists from a variety of fields are needed to determine if a liver transplant is appropriate. The evaluation includes a review of your medical history and a variety of tests. The transplant team will arrange blood tests, X - rays, and other tests to help make the decision about whether you need a transplant and whether a transplant can be carried out safely. Other aspects of your health—like your heart, lungs, kidneys, immune system, and mental health—will also be checked to be sure you're strong enough for surgery.

Many healthcare facilities offer an interdisciplinary approach to evaluate and to select candidates for liver transplantation. This interdisciplinary healthcare team may include the following professionals:

• Liver specialist (hepatologist).
• Liver Transplant surgeons
• Transplant coordinator, usually a registered nurse who specializes in the care of liver-transplant patients (this person will be your primary contact with the transplant team).
• Psychiatrist to help you deal with issues, such as anxiety and depression, which may accompany the liver transplantation.
• Anesthesiologist to discuss potential anesthesia risks.

Can anyone with liver problems get a transplant?

You cannot have a transplant if you have

• cancer in another part of your body
• serious heart, lung, or nerve disease
• active alcohol or illegal drug abuse
• an active, severe infection
• inability to follow your doctor's instructions

How is the transplant decision made?
The decision is taken in consultation with all individuals involved in the patient's care, doctors as well as the patient’s family. The patient and family's input is vital and it is important that they clearly understand the risks & benefits involved with transplantation.

Will liver transplantation be a treatment of last resort, when everything else has failed?
The answer would be both yes and no. If medical treatment is thought to prolong survival with good quality of life, transplantation would be considered at a later stage in the future. However, ideally, the surgery is undertaken before the terminal stage of the disease when the person is too ill to withstand major surgery. For patients with poor quality of life due to complications arising from liver cirrhosis, liver transplantation should be undertaken at an optimal state of health for a good prognosis.

Is Liver transplant Legal in India?

Yes, liver transplant is legal in India but is bound by certain clauses which have been framed to prevent commerical use of organs. On July 8, 1994, the President of India assented to the Transplantation of Human Organs Act (Act No.42, 1994) providing for "the regulation of removal, storage and transplantation of human organs for therapeutic purposes and for the prevention of commercial dealings in human organs and for matters connected therewith or incidental thereto". As a result, various state legislatures prohibited all organ sales.

The Act's preamble envisages the object of the legislation in a two-fold manner:
(1) Providing for regulation of removal, storage and transplantation of human organs for therapeutic purposes; and
(2) prevention of commercial dealings in human organs.

The Act necessitates that the donor must not be below 18 years of age, must agree voluntarily to his organ removal, and that his consent is informed. It further prohibits removal of organs by anyone other than a registered medical practitioner, and the transplantation must take place in a registered hospital.

Further, to prevent commercialisation of sales of human organs, Sections 18 & 19 criminalises such transactions, including supply of organs for payment, and making/receiving any such payment. Payment, however, does not include reimbursement for the cost of removing, transporting or preserving the organ to be supplied or any expenses/loss of earnings incurred by the donor which can be attributed to his supplying any organ from his body.

Section 9(1) provides that no human organ shall be removed and transplanted unless the donor is a close relative as defined in section 2(i) of the Act. And though an altruistic donor is permitted to donate organs, it is only with prior authorisation of the committee constituted under the Act. Section 9(5)&(6) lay down the procedure to be followed while obtaining the committee's approval.

How long does it take to get a new liver?

If you become an active liver transplant candidate, your name will be placed on a waiting list kept at the United Network for Organ Sharing (UNOS). Patients are listed according to blood type, body size, and medical condition (how ill they are). Each patient is given a priority score based on three simple blood tests (creatinine, bilirubin, and INR). The score is known as the MELD (model of end stage liver disease) score in adults and PELD (pediatric end stage liver disease) in children.

Patients with the highest scores are transplanted first. As they become more ill, their scores will increase and therefore their priority for transplant increases, allowing for the sickest patients to be transplanted first.

It is impossible to predict how long it will take for a liver to become available. Your transplant coordinator will always be available to discuss where you are placed on the waiting list. If you need a transplant, your name will be placed on a national waiting list. While you wait for a new liver, it would be best if you and your doctor discuss what you can do to stay strong for the impending surgery. You can also begin learning about taking care of a new liver. For information regarding the national waiting list and patient rankings, please contact UNOS.

Where does a liver for transplant come from?

There are two types of liver transplant options: living donor transplant and deceased donor transplant.

Living donor

Living donor liver transplants are an option for some patients with end-stage liver disease. This involves removing a segment of liver from a healthy living donor and implanting it into a recipient. Both the donor and recipient liver segments will grow to normal size in a few weeks.

The donor, who may be a blood relative, spouse, or friend, will have extensive medical and psychological evaluations to ensure the lowest possible risk. Blood type and body size are critical factors in determining who is an appropriate donor. All living donors and donated livers are tested before transplant surgery. The testing makes sure the liver is healthy, matches your blood type, and is the right size so it has the best chance of working in your body.

Recipients for the living donor transplant must be active on the transplant waiting list. Their health must also be stable enough to undergo transplantation with excellent chances of success.

Deceased Donor.

In deceased donor liver transplant, the donor may be a victim of an accident, brain hemorrhage or head injury. The donor's heart is still beating, but the brain has stopped functioning. Such a person is considered legally dead, because his or her brain has permanently and irreversibly stopped working. At this point, the donor is usually in an intensive-care unit. The liver is donated, with the consent of the next of kin, from such individuals. Whole livers come from people who have just died. This type of donor is called a cadaveric donor. The identity of a deceased donor and circumstances surrounding the person's death are kept confidential.

Do the donor and the recipient have to be matched by tissue type, sex, age, etc.?
No. For liver transplants, the only requirements are that the donor and recipient need to be of approximately the same size, and of compatible blood types. No other matching is necessary.

What happens if there are two suitable recipients for a donated liver?
This is unusual in practice but the decision would be to transplant the patient with the more urgent need. A small group of patients who are critically ill from acute liver disease have the highest priority on the waiting list.

Is liver donation safe?

Liver donation is very safe. This is because the liver has great reserve and regenerates to its original size quickly (within 2-3 months) after a part of it is removed. The donor suffers from no long-term effects, does not have to take any medication beyond 2-3 weeks, and is back to normalcy in a month. He/she can resume strenuous physical activity (weight lifting etc) in 3 months

What are some of the major risks pre and post surgery?
Prior to surgery, the prime risk is the development of some acute complication of liver disease, which might render the patient unacceptable for surgery. With transplantation there are risks common to all forms of major surgery. In addition, there maybe technical difficulties involved in removing the diseased liver and implanting the donor liver. One of the major risks the patient faces is not having any liver function for a brief period. Immediately after surgery, bleeding, poor function of the grafted liver, and infections are major risks. The patient is also carefully monitored for several weeks for signs of rejection of the liver.

What are the overall chances of surviving a liver transplant?
It is difficult to say as this depends on several factors but overall 85 - 90 percent of children & adults do well enough to be discharged from the hospital.

What about Health Insurance?

You will need to check your health insurance policy to be sure it covers liver transplantation and prescription medicines. This is because you will require many prescription medicines after the surgery and for the rest of your life.

What happens in the hospital?

When a liver has been identified for you, you will be prepared for surgery. When you arrive at the hospital, additional blood tests, an electrocardiogram, and a chest X-ray will generally be taken before the operation. You may also meet with the anesthesiologist and a surgical resident. If your new liver is from a living donor, both you and the donor will be in surgery at the same time. If your new liver is from a person who has recently died, your surgery starts when the new liver arrives at the hospital.

How long would surgery take?

Liver transplants usually take from 4 to 14 hours. During the operation, surgeons will remove your liver and will replace it with the donor liver. The surgeon will disconnect your diseased liver from your bile ducts and blood vessels before removing it. The blood that flows into your liver will be blocked or sent through a machine to return to the rest of your body. The surgeon will put the healthy liver in place and reconnect it to your bile ducts and blood vessels. Your blood will then flow into your new liver. Because a transplant operation is a major procedure, surgeons will need to place several tubes in your body. These tubes are necessary to help your body carry out certain functions during the operation and for a few days afterward.

What happens during this recovery period?

Initially in the intensive care unit there is very careful monitoring of all body functions, including the liver. Once the patient is transferred to the ward, the frequency of blood testing, etc. is decreased, eating is allowed and physiotherapy is prescribed to regain muscle strength. The drug or drugs to prevent rejection are initially given by vein, but later by mouth. During the transplantation, frequent tests are done to monitor liver function and detect any evidence of rejection.

When will I be able to go home?

The average hospital stay after liver transplant is two weeks to three weeks. Some patients may be discharged in less time, while others may be in the hospital much longer, depending on how the new liver is working and on complications that may arise. You need to be prepared for both possibilities. Once you are transferred from the intensive-care unit to the regular nursing floor you will be given a discharge manual, which reviews much of what you will need to know before you go home. In the hospital, you will slowly start eating again. You will first start with clear liquids, then switch to solid food as your new liver starts to function.

You will learn how to take care of yourself and to use your new medications to protect your new liver. As you perform these functions regularly, you will become an important participant in your own healthcare. Before your discharge, you will also learn the signs of rejection and infection and will know when it is important to call your doctor. The patient's willingness to stick to the recommended post-transplantation plan is essential to a good outcome.

From the description, patients with successful liver transplants seem very healthy. How long can this good health last?
The newness of this procedure makes this question difficult to answer. There is every indication that those who are well after one year will continue to remain so indefinitely.

What Complications Are Associated With Liver Transplantation?
Two of the most common complications following liver transplant are rejection and infection.

What is rejection?

When the liver is transplanted from one person (the donor) into another (the recipient), the immune system of the recipient triggers the same response against the new organ that it would have against any foreign material, setting off a chain of events that can damage the transplanted organ. This process is called rejection. It can occur rapidly (acute rejection), or over a long period of time (chronic rejection). Rejection can occur despite close matching of the donated organ and the transplant patient.

Your body’s natural defences, the immune system works to destroy foreign substances that invade your body. The immune system, however, cannot distinguish between your transplanted liver and unwanted invaders, such as viruses and bacteria. Therefore, your immune system may attempt to attack and destroy your new liver. This is called a rejection episode. About 70% of all liver-transplant patients have some degree of organ rejection prior to discharge. Anti-rejection medications are given to ward off the immune attack.

How is rejection prevented?
After the liver transplant, you will receive medications called immunosuppressants. Immunosuppressants weaken your immune system's ability to reject your new liver. These medications slow or suppress your immune system to prevent it from rejecting your new liver. Immunosuppressant drugs greatly decrease the risks of rejection, protecting the new organ and preserving its function. These drugs act by blocking the recipient's immune system so that it is less likely to react against the transplanted organ. A wide variety of drugs are available to achieve this aim but work in different ways to reduce the risk of rejection. They may include steroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil. You must take these drugs exactly as prescribed for the rest of your life.

Do immunosuppressants have any side effects?

Immunosuppressant drugs lower a person's resistance to infection and can make infections harder to treat. Although these medications are meant to prevent rejection of the liver, they also decrease the ability of the body to fight off certain viruses, bacteria, and fungi. The organisms that most commonly affect patients are covered with preventive medications. However, avoiding contact with people who have infections is very important.

Patients who are taking immunosuppressant drugs should see their doctor on a regular basis. Periodic checkups will allow the physician to make sure the drug is working as it should and to monitor the patient for unwanted side effects. These drugs are very powerful and can cause such serious side effects as high blood pressure, rise in cholesterol levels, diabetes, weakening of bones, kidney problems and liver disorders. Various medicines are used, and each has its own effects. Cortisone-like drugs produce some fluid retention and puffiness of the face, risk of worsening diabetes and osteoporosis (a loss of mineral from bone). Cyclosporine produces some tendency to develop high blood pressure and the growth of body hair. The dose of this medication must be very carefully regulated. Kidney damage can occur from cyclosporine but this can usually be avoided by monitoring the drug levels in the blood. Common side effects for FK-506 include headaches, tremor, diarrhea, increased tension, nausea, increased levels of potassium and glucose and kidney dysfunction. Steroid drugs may also cause changes in how you look by causing weight gain. Some side effects may not show up until years after the medicine was used.

The drugs can also increase the chance of uncontrolled bleeding. Some ways of preventing infection and injury include washing the hands frequently, avoiding sports in which injuries may occur, and being careful when using knives, razors, fingernail clippers, or other sharp objects.

Immunosuppressant drugs are also associated with a slightly increased risk of cancer because the immune system plays a role in protecting the body against some forms of cancer. Other side effects of immunosuppressant drugs are minor and usually go away as the body adjusts to the medicine. These include loss of appetite, nausea or vomiting, increased hair growth, and trembling or shaking of the hands. Medical attention is not necessary unless these side effects continue or cause problems.

Do recipients of liver transplant have to take these medicines for the rest of their lives?
Usually, yes. However, as the body adjusts to the transplanted liver, the amount of medication required to control rejection can be gradually decreased. There are patients who have been successfully taken off these drugs. Researchers are attempting to determine the causes of success in these cases.

What are the signs and symptoms of rejection?

Here is a list of signs and symptoms that may indicate liver graft rejection:

• Fever greater than 100°
  
• Fatigue or excess sleepiness
  
• "Crankiness"
  
• Headache
  
• Abdominal swelling, tenderness, or pain
  
• Decreased appetite
  
• Jaundice (yellow skin or eyes)
  
• Dark (brown) urine
  
• Itching
  
• Nausea
  

None of these symptoms are specific for rejection; but they are important enough that when they occur, they should prompt a call to your doctor who will decide whether the situation warrants further investigation or should be observed for the time being.

It is very important to realize that rejection of transplanted liver is quite variable. Some patients will feel perfectly well, only to discover that their liver is being attacked by their immune system. In fact, it is more likely than not that there will be minimal or no symptoms of rejection.

Since rejection may have no symptoms at all, the standard strategy for post-transplant care is to regularly run blood tests that may be early indicators of liver graft rejection. Doctors will check your blood for liver enzymes, the first sign of rejection. In the beginning, these tests are run daily. For the first month or so after a liver transplant the tests are run at least weekly. Gradually the interval between measurement is increased as the months and years pass. When rejection is suspected it can be confirmed by a liver biopsy. In some instances a biopsy is not needed because rejection is strongly suspected. In other situations, a biopsy is critical. For a biopsy, the doctor takes a small piece of the liver to view under a microscope.

What are the other problems that can damage the liver transplant?

Onset of the problem that made the transplant necessary in the first place is the most common trouble for patients with liver transplants. Also, hepatitis C virus may damage a transplant if the patient was infected before the operation took place.

Other problems include

• blockage of the blood vessels going into or out of the liver
• damage to the tubes that carry bile into the intestine

Is a recurrence of the original disease in the transplanted liver likely?

If the disease was caused by hepatitis B or hepatitis C viruses then recurrence is likely. Other types of liver disease do not recur.

What if the transplant doesn't work?

Optimism is the need of the hour. Most liver transplant operations go well. About 80 to 90 percent of transplanted livers are still working after 1 year. Sometimes the liver takes a long time to work. There are varying degrees of failure of the liver, however, and even with imperfect function, the patient will remain quite well. If there are complications – say, the new liver fails to function or your body rejects it, your doctor and the transplant team will decide whether to replace the failing transplanted liver by a second (or even third) transplant operation. Unfortunately, there is no dialysis treatment for livers as is possible with kidneys. Researchers are experimenting with devices to keep patients with failing livers alive while waiting for a new liver.

How do I take care of my liver after I leave the hospital?

After you leave the transplant center at the hospital, you will need to visit your doctor often to be sure your new liver is working well. You will also need to have regular blood tests to check that your new liver is not being damaged by rejection, infections, or problems with blood vessels or bile ducts. You will need to be careful about avoiding sick people and must immediately report any signs of illnesses to your doctor. Home care involves building up endurance to carry out daily life activities and recovering to the level of health that the patient had before surgery. This can be a long, slow process that includes simple activities. Walking may require assistance at first. Coughing and deep breathing are very important to help the lungs stay healthy and to prevent pneumonia. Diet may at first consist of ice chips, then clear liquids, and, finally, solids. It is important to eat well-balanced meals with all food groups. After about 3-6 months, a person may return to work if he or she feels ready and it is approved by the primary doctor. Besides a healthy diet and exercise you must abstain from alcohol, especially if alcohol was the primary cause of damage to your own liver. Before you take any medication, including ones you can buy without a prescription, you will need to check with your doctor whether it is safe for you. It is most important to diligently follow all that your doctor says to take good care of your new liver.

Can I go back to my daily activities?

Certainly. After a successful liver transplant, most people are able to go back to their normal daily activities. Getting your strength back will take some time, depending on how sick you were before the transplant. Your doctor will be able to tell you how long your recovery period is likely to be.

• Work- After recovery, most people are able to resume work.
• Diet - Most people can go back to eating as they did before. Some medication may cause weight gain, others may cause diabetes or a rise in your cholesterol. Meal planning and a balanced low-fat diet can help you remain healthy. Transplant patients have a tendency to gain weight because of their retention of water. They are advised to lower their intake of salt to reduce or eliminate this water retention.
• Exercise- Most people can engage in physical activity after a successful liver transplant.
• Sex- Most people return to a normal sex life after liver transplantation. It is important for women to avoid becoming pregnant in the first year after transplantation. You should talk to your transplant team about sex and reproduction after transplantation.

For further clarifications do consult your doctor before beginning any new activity.

How safe is it for women to become pregnant after transplantation?

Studies have shown that women who undergo liver transplantation can conceive and give birth normally, although they have to be monitored carefully because of a higher incidence of premature births.
Mothers are advised against nursing babies because of the possibility of immunosuppressive drugs being transmitted to the infants through breast milk.

How can I donate my organs?

If you wish to be an organ donor, ensure that you carry an organ donor card and paste an organ donor sticker on your medical identification card. It is also important to discuss your views on organ donation with immediate family members since the process cannot be carried out without their consent. An organ donor card is easily available at the MOHAN Foundation.

FAQ's - Pediatric Liver transplant