The first liver transplant (= OLT = orthotopic liver transplant) in Switzerland was carried out at the Inselspital in Bern in 1983. Over the 15 years since then, patient survival rates have improved drastically thanks to the standardisation of the surgical procedure, advances in the fields of intensive care and anaesthetics, and better immuno-suppressive drugs. Only a few years ago, the operation required 10 to 15 hours, enormous quantities of blood and blood preparations had to be administered, and patients often had to remain in hospital for several months following the transplant.

Today, a liver transplant can quite easily be compared with any other major abdominal operation. Surgery lasts between 4 and a maximum of 7 hours, the time spent in intensive care is from 1 to a maximum of 3 days, and on average patients can be discharged to go home after 10 to 14 days. The results in relation to patient survival rates and quality of life after an OLT are also highly satisfactory. The first year survival rate for patients who receive a transplant at our clinic amounts to over 96% (after 5 years 94%) and thus far exceeds the international average. In only a few weeks following the OLT, 95% of patients can go about their lives without requiring help from relatives, home helps or assistants provided by their health insurance company, and within a few months they can return to their jobs.

Criteria (Indications)
Nowadays, a liver transplant is the preferred therapy in the treatment of various disorders of the liver which have reached their terminal stage, as well as for acute liver failure. Six main indications (reasons) for liver transplantation can be distinguished. In the event that one or more of these symptoms are present, the patient qualifies for a liver transplant.
· Recurrent encephalopathy (slowing of the processes of the brain, lack of concentration, confusion leading to clouding of consciousness, coma)
· Portal hypertension with oesophageal variceal bleeding and/or untreatable abdominal dropsy and episodes of peritonitis
· Seriously increased bilirubin
· Seriously limited performance of synthesis by the liver, indicated above all by coagulation defects in synthesis and low albumin
· Unacceptable quality of life (physical weakness, exhaustion, feeling of illness, unbearable itching etc.)
· Growth disorders in the case of children

Exclusion criteria (contraindications)
Certain circumstances or illnesses mean that a liver transplant must be ruled out. Here we draw a distinction between absolute and relative contraindications:
Absolute contraindications:
· Advanced heart/lung disease
· Septicaemia (blood poisoning caused by bacteria, viruses or fungi)
· Tumours located outside the liver
· Active abuse of alcohol, drugs or medication
· Untreatable psychiatric disorders
· Patient is HIV - positive
· Patient shows a clear lack of reliability
Relative Contraindications:
· Age over 65
· Portal vein thrombosis
· Lack of support in the social sphere (from family, cohabitee etc.)

Risk factors
The following risk factors are considered on a case to case basis but would not mean that a liver transplant would be excluded from the outset:
· Kidney function disorders
· Previous operations on the hepatic portal
· Active oesophageal variceal bleeding
· Serious malnutrition, emaciation
· Diabetes mellitus
· Combined organ transplantation e.g. liver and kidney, liver and heart etc.

Before the Transplant

Examination with a view to a liver transplant
Before being placed on the waiting list, certain important tests are necessary to clarify whether all the medical preconditions for transplantation have been fulfilled and that there are no further disorders which would make it impossible to carry out a liver transplant. These tests require around 4 - 5 days to be carried out. The patient is admitted to the Clinic for Visceral and Transplant Surgery for this purpose and there receives a written summary of the planned tests from the nursing staff. This period in hospital allows both the patient and the doctors and nurses a chance to get to know each other and form a relationship of trust. Mutual trust both before and after the operation is a significant factor in the success of a liver transplant.

The following tests are carried out
· Complete laboratory analysis of blood, urine and faeces
· Various x-ray and ultrasound tests such as ultrasound of the liver (to determine the size of the organ, blood flow and to exclude tumours) X-ray of the lungs, the nasal sinuses and the teeth in order to rule out possible sources of infection.
· Endurance-ECG and ultrasound of the heart
· Lung function test and blood gas analysis
· Gastroscopy
· Coloscopy in the case of patients over 50 years of age (risk of tumours)
· Bone densitometry to measure the bone density (osteoporosis yes/no?)
· Electroencephalogram (EEG) measurement of brain activity
· Examinations by an: opthalmologist, ear-nose-throat specialist, dentist and psychiatrist
· Consultations with the anaesthetist, renologist (kidney specialist) and with the haematologist (blood specialist)
· Dietary counselling
· Consultations with the social worker, the surgeon and the transplant coordinator

In certain cases, additional tests (e.g. contrast medium x-rays of the abdominal organs etc.) are required. The results of all these tests are submitted to the transplant team (see below) at a meeting. Together the team assesses with the aid of the results whether a liver transplant is the correct form of treatment for the patient or whether other forms of treatment should be considered.

The Transplant Team

In the broadest sense, all the people who are involved in the investigatory tests belong to the transplant team, as an operation as complex as a liver transplant can only be carried out with the best of cooperation and communication. The smaller group that is later responsible for care of the patient before and after the operation is composed of hepatologists, transplant surgeons, nurses in the intensive care unit and department, the anaesthetists and intensive care doctors, and the social worker and the transplant coordinator.

The time on the waiting list

Patients who qualify for a liver transplant are registered on the central, national waiting list of Swisstransplant. The personal data which are necessary in order to obtain a suitable donor organ are the age, height, weight and blood group of the possible organ recipient. Patients are provided with a pager by the transplant coordinator in order that they can be contacted at any time during the waiting period without having to restrict their activities. The time it takes before a suitable donor liver is available is very difficult to predict. It varies from a few days or weeks to several months.
During this time, the patient undergoes medical examinations and receives medical care at regular intervals from the doctors in the hepatology out-patients department. Waiting for a transplant is normally very stressful. In order that our patients cope well with the wait both physically and mentally, we make the following recommendations:
· Strict compliance with the doctors' instructions (hepatologists, family doctor) in relation to the taking of medicines, limits on the fluid intake etc.
· In the case of symptoms such as high temperature or weight gain, contact the doctor dealing with the case immediately
· As much physical exercise as is possible (non-strenuous sport, walking)
· Follow advice on diet
· Continue to work and pursue leisure time interests as much as possible

The better the physical and mental condition before the operation is, the quicker the recovery progresses afterwards.

Ranking on the waiting list

Often patients ask anxiously about the place they occupy on the waiting list. No such ranking actually exists, and it is unimportant whether a patient's name appears in the first or twentieth place on the list, as only the medical criteria are relevant. When a donor organ becomes available, the first step is to compare the blood group and height of the donor and the recipient. If there are several suitable recipients on the waiting list, the medical condition of the patients decides who is to receive the organ.
Patients with acute liver failure have a special rank or status. As this is an acute life-threatening condition, and these patients need an emergency liver transplant with 24 to 72 hours, the so-called "super urgent" status applies here. This means that notice of any liver available in Switzerland will firstly be given to the center with the emergency patient, and these patients have top priority. The National Coordination Office of Swisstransplant will also notify emergency recipients in neighbouring countries.

The Call to Hospital

If a suitable organ is found, the patient will be contacted by the transplant coordinator by telephone or using the pager. The coordinator will tell the patient when he or she should be in the hospital and where the admission formalities will be dealt with. There will be enough time for the patient to get ready calmly and to organise transport to the hospital. Patients are instructed not to eat or drink anything more after the telephone call.

Preparations for the operation

The patient is met by the transplant coordinator at reception and taken to the department. There everything has been prepared by those responsible for the required pre-operative tests (blood tests, chest x-ray, ECG and if necessary an ultrasound scan of the liver). The departmental doctor will examine the patient, explain the transplant procedure again, together with the risks, and obtain his or her written consent for the operation to go ahead. It can only be certain that the transplant will be performed or not when the liver from the donor has been assessed by the surgeon. As the removal of the organ from the donor and the preparations for the transplant progress to some extent in parallel, a few hours can pass before a final decision can be made.

Occasionally, it is discovered during the removal operation that the donor liver does not meet the clinical requirements, and the liver transplant unfortunately has to be called off at short notice. Our patients receive detailed information about this eventuality, but nevertheless disappointment after all the hope and excitement is understandable. We hope, however, that our patients will have faith in our decision, as a positive operative result is dependent on the patient receiving a first-class organ that functions well.

The liver transplant

The transplant is performed under general anaesthesia and takes from 4 to 6 hours. In the first stage, the diseased liver is removed. In order to make the implantation of the new liver easier and to avoid serious loss of blood, the venous blood in the lower half of the body which normally flows into the liver and then into the heart is often diverted from the area of the operation using a pump in order that it can circulate outside the body.

The donor liver is then joined to the circulation of the recipient by four vascular sutures. The bile duct of the donor liver is thereafter joined to that of the recipient. In order to splint the suture, a so-called T-drain is attached, through which the bile drains away to a bag outside the body. This has the advantage that we can assess the colour and composition of the bile and decide whether the transplanted liver is functioning properly. In the case of patients with primary sclerosing cholangitis, the bile duct of the new liver will be connected directly to the small intestine (Y-Roux). After inserting the drainage tubes that are intended to drain the secretions from the wound away to the outside of the body, the operation area is closed up.

After theTransplant

The intensive care unit
After the operation the patient wakes up in the intensive care unit. For 1 to 3 days, the patient remains here while cardiovascular and lung function and the fluid balance are monitored and stabilised. As the patient's own ability to breathe is insufficient immediately after the operation (due to the anaesthetics), the patient will be supported by a ventilator for a few hours. Other than the wound drainage and the ventilator tube, after they wake up patients find that they have a catheter to monitor blood pressure and to drain away urine, a catheter to measure cardiac pressure and for the administration of liquid medicines, and a stomach tube. These tubes will be removed as quickly as progress allows, in order to keep the risk of infection as low as possible. In the first few hours after the operation patients feel tired and weak, but even on the day of the operation a start will be made with breathing exercises and mobilisation.

Medical and nursing care in the transplantation department
After an average of 1-3 days, patients are moved from the intensive care unit to the transplantation department. How soon the move can be planned for the most part depends on the patients themselves. The nursing staff help patients to regain their independence as quickly as possible. Patients learn very quickly to take their medicines according to the plan and without any assistance. The visits from the transplant team take place twice a day, at 8.00 a.m. and at 5.00 p.m. The patients are examined and additional treatments decided on.

Labortests und Untersuchungen
Laboratory tests and investigations Blood is taken for testing on a daily basis in order to check the functioning of the liver and the kidneys and to determine the medicines to be administered. In addition, in the first post-operative week, two important routine tests are carried out.
1. T-Drain-Cholangiography
This examination is carried out on the fifth day following the operation. It involves a painless x-ray investigation of the bile ducts using a contrast medium. It allows a check to be made on whether the bile is flowing unobstructed or whether there is any constriction of the bile ducts. After the examination the drainage tube will be sealed up, and the bile is no longer made to flow into a bag, but can flow naturally into the small intestine. The bile drain is left in place for a further 3 months. In order to remove it after this period, the patient will have to come into hospital again for one day.
2. Liver biopsy
On the seventh post-operative day, an ultrasound controlled liver biopsy is carried out. Other than a little pinprick for the local anaesthetic, the patient should feel little in the way of discomfort. The liver tissue obtained is then tested in the microbiology laboratory for bacterial and viral pathogens and in the pathology laboratory for any indications of rejection.

Preparations for discharge from hospital
Normally, discharge from hospital can be planned after 8 to 10 days, which means that patients can on average leave the hospital after 12 to 14 days. This is of course dependent on recovery progressing without any complications such as an infection or a rejection reaction.
Before discharge, patients learn how to take their medicines, how to rinse out and change the dressing on the T-Drain, and some rules on how they should modify their behaviour in their daily lives. The nursing staff prepare patients carefully for discharge from the hospital. Our social worker is also available in case support is needed for the initial period at home. A special recuperative period following the stay in hospital is not required, as it is basically better for recovery if patients return to their normal daily lives within their families as quickly as possible. Before discharge an appointment for the first check-up in the hepatology out-patients department will be organised. The patients will receive a prescription for their medicines and if they are released at the weekend they will be given an adequate supply of dressings and medication to cover the first few days. In addition, they will be given a list of telephone numbers to be used in the case of any "emergencies" (high temperature, vomiting etc.).

After the transplant

Return to normal life
We recommend that out patients should return to their normal lives as soon as possible after discharge from hospital. Patients can judge for themselves what they are capable of achieving. Light housework, walking or other physical exercise combined with a healthy diet promotes the building of muscles and contributes to the patient soon being able to live a normal life and return to work. A few rules must nevertheless be followed after the transplant:
· If the patient's temperature rises to over 38.5 °C the transplantation center must be contacted immediately (during the day: duty doctor in the hepatology out-patients department; at night: duty doctor in the transplant surgery section). A raised temperature can indicate a rejection reaction or infection, so any increase in temperature must be medically investigated immediately and a suitable treatment begun.
· As the medicines are taken in high dosages to begin with, large gatherings of people and people with viral infections (influenza, childhood diseases) should be avoided in the first few months.
· Avoid sunbathing for long periods of time (increased risk of skin cancer due to the consumption of immuno-suppressant drugs)
· Follow the recommendations of the nursing staff in relation to bodily and oral hygiene
· Enjoy a new life

Working life
The time required before patients can start work again is very much dependent on the type of work involved, whether it is a sedentary occupation or whether it involves major physical activity. Normally, however, patients are in a position to go back to work after 6 months at the most. Generally it is our aim to allow patients with liver transplants to lead a normal productive life. In principle, patients should avoid lifting heavy weights for four to six months, as due to the delayed healing of the wound, there is a danger of an incisional hernia (a complication commonly encountered after a liver transplant, above all in the case of men).

Sexual Relations
The speed with which patients resume their sexual activities after the transplant very much depends on the recovery process and is determined by the patients themselves. From a medical point of view, there is no reason not to have an active sex life. Some men can become impotent as a result of liver disease, and physical weakness and tiredness also contribute to the problem. After the transplant, sexual potency normally returns. Certain medication such as that for high blood pressure or high dosages of steroids can however prolong the period of impotence following a liver transplant. Women who have stopped menstruating due to liver disease will begin to have periods again within a few months of the transplant after the functioning of their organs and their hormonal balance normalises. Even though the cycle can be irregular, ovulation and therefore fertilisation is possible. It is therefore essential for sexually active patients of child-bearing age to use some form of contraception. The method used should always be discussed with a doctor. The contraceptive pill is often incompatible with immuno-suppressant drugs and is not suitable as a means of contraception most particularly because of its effect on the liver. An intrauterine device (coil) is not suitable because of the increased risk of infection. What is recommended is a combination of the use of condoms, the diaphragm and spermicidal creams. If it is decided not to have any children, surgical sterilisation (tubectomy, vasectomy) is the safest method. For patients who are sexually active but who have no permanent partner, it is vital that condoms are used as a protection against sexually transmitted diseases (AIDS, syphilis, gonorrhoea, hepatitis or herpes).

Pregnancy
Women are advised to avoid becoming pregnant for at least two years after the transplant, as by this time the immuno-suppressant drugs are normally only given in small doses. A pregnancy should always be planned and the possible risks must be discussed with the hepatologist dealing with the case. Despite the increased risks for both mother and child, it is possible to carry a healthy child to the full term following a liver transplant. The initially high dosage of immuno-suppressants can damage the genetic make-up of the sperm or even the sperm themselves. Therefore, men who have had transplants should wait before fathering children until the dosage of the medication has been significantly reduced. In comparison with the rest of the population, there is very little increased risk of malformation in the children of couples where either the man or the woman has had a liver transplant.

Check-ups in the hepatology out-patients department (clinical pharmacology)
The follow-up examinations initially take place in the clinical pharmacology out-patients department once or twice a week. At these check-ups, the vital signs (blood pressure, pulse, temperature etc.), the region of the wound, the combination of medicines (Neoral or Prograf) and the blood values are tested. The patients arrive for the check up having had nothing to eat or drink and bring their morning dosage of medication with them. After a sample of blood is taken, they are given a small snack and can then take their tablets. If the dosage of immuno-suppressants has to be changed to accord with the current composition of the blood, the patient will be informed of this by telephone by the doctor responsible the same afternoon. As soon as the condition of the patient has stabilised, after a few weeks the check-ups will increasingly be taken over by the patient's family doctor.

Medication and Complications

Medication General Guidelines
The patients themselves are responsible for the correct consumption of the medication prescribed and will receive precise instructions from nursing staff when being prepared for discharge on:
· The name and effect of the medication
· When
· How
· and for how long the medication must be taken
· The main side-effects
· What to do if you forget to take your medication

Immuno-suppressants
These drugs suppress the rejection reaction and are the "life insurance" of the transplant patient, so to speak. In the initial months after the transplant, the patients receive a combination of three immuno-suppressant drugs. According to how matters progress, the dosage will be reduced after a while, or the patient may even stop taking one or two of the drugs.
Cyclosporin-A (brand name: Neoral, Sandimmune)
Cyclosporin-A is one of the most important immuno-suppressants, drugs which inhibit the body's immune defences. It prevents the transplanted liver from being recognised by the organism as a foreign body and the immune defences thus being activated. It specifically affects the T-cells of the immune system.
Main side-effects:
· Increased risk of infection
· Increased risk of high blood pressure and kidney disorders
· Swollen gums
· Increased growth of hair all over the body
· Severe trembling of the hands can be an indication that there is too much cyclosporin in the bloodstream

Azathioprin (brand name: Imurek)
Imurek is also a drug which suppresses the immune defences, and which prevents formation of nucleic acid (main component of DNA). DNA is mainly formed in cells which divide quickly. As the immune system also consists of fast-dividing cells, taking Imurek prevents cell multiplication. Due to the effect on the bone marrow, Imurek can drastically reduce the number of white blood cells and blood platelets.
Main side-effects
· Increased risk of infection due to the reduction in white blood cells
· Nausea, vomiting
· Bleeding tendency due to reduction in blood platelets

Corticosteroid (brand name Prednison, Prednisolon)
This is a hormone which is itself produced by the body in small quantities in the adrenal gland. It has an important influence on the infection and immune processes in the body.
Side effects:
· Retention of salt and water in the body, possibly leading to oedemas in the legs and back of the feet.
· Gastric ulcers (to prevent this medication will be prescribed to reduce the production of gastric acid)
· Increase in blood sugar level (in some cases a special diet may be required or it may be necessary to administer insulin for a temporary period)
· Swelling up of the face (moon face) This symptom disappears as the dosage is reduced
· Muscle weakness
· Night sweat, nightmares
· Delayed healing of the wound
· Acne
· Increase in appetite

Tacrolimus oder FK-506 (brand namePrograf)
Prograf is very similar to cyclosporin in its effects and side-effects. Patients are prescribed either cyclosporin or Prograf. Some basic differences of Prograf are:
· The incidence of high blood pressure is lower
· The incidence of increased blood sugar levels is higher
· Neurological disorders such as trembling, headaches, and nightmares are sometimes more common

Rejection reaction

Around 50% of transplant patients experience a rejection reaction in the early post-operative phase.
Rejection is a reaction of the immune system. The immune system recognises the transplanted liver as something "foreign" and then mobilises certain cells to attack the new organ. While the patient is in hospital, any rejection will be very quickly detected in the daily examinations. Often such a reaction begins with a rise in temperature. Rejection can be dealt with very effectively by giving the patient medication. The patient receives high dosages of cortisone over 3 to 5 days.

The first 12 months after the transplant is the most likely time for a rejection reaction. As any rejection must be treated immediately, patients are instructed to keep a close watch on their temperature at home and to inform the transplant center without delay if it rises to over 38.5 °C. In most cases the patient has to come into hospital in order for the required diagnosis to be made and the rejection to be treated, but often all that is needed is an increase in the dosage of steroids in order to bring the immune reaction under control.

Infection

Infection
As the natural defences against infection are weakened by the immuno-suppressants, the risk of infection is very high. A distinction is made according to the type of pathogen between viral, bacterial and fungal infections, with fungal infections being the most feared, as they are very difficult to treat. Common viral infections after transplants are:

Cytomegalovirus infection(CMV)
The cytomegalovirus is a herpes virus. Around 50% of the population are carries of this virus, but it only becomes active when the immune defences are weakened, such as in the case of transplant patients, the elderly and the very young. The risk of infection is at its highest in the first few months after the transplant. The symptoms are: high temperature, tiredness, pain in the joints, headaches, visual disturbances and pneumonia.

Herpes simplex infection type I + //
Herpes simplex type I very commonly affects the skin of the face (cold sores), but can also infect the eyes and the lungs. Type II normally causes genital infections (sexual transmission!). Most infections with H. simplex are very mild. The main symptoms are: painful blisters filled with fluid on the mouth or genitals.
Treatment: ZoviraxÒ (cream, tablets or injection)

Herpes zoster (shingles)
Shingles appears as a reddening of the skin or as fluid-filled pustules mainly on the chest, the back or on the hips. Symptoms: severe pain, erythema, high temperature
Treatment: according to the symptoms

Bacterial infections
Candidasis
Among the possible bacterial infections, infections of the wound (the surgical incision) stand at the forefront. Symptoms: reddening, swelling, pain and possible pustulant discharge from the region of the wound. Treatment: antibiotics, after the nature of the bacilli has been determined by a surface biopsy of the wound

Pseudocystis carinii
Pseudocystis carinii is a fungal-type bacillus which can cause serious pneumonia. Symptoms: a dry cough and high temperature. Treatment: prevention (part of the medication after the transplant)

Bacterial Infections
The most common of the bacterial infections are infections of the wound (operation scar). Symptoms: reddening, swelling, pain and/or discharge of pus from the region of the wound. Treatment: antibiotics after the nature of the bacilli has been determined by a surface biopsy.

Surgical complications

Bile leakage
Bile leakage is when bile accumulates outside the bile ducts. This is indicated by pain in the region of the liver, nausea, vomiting and a high temperature.

Bile duct stenosis
The constriction of the bile duct close to the anastomosis (junction), which can prevent the bile from draining away. It can often be treated by endoscopic dilation or by inserting a small tube. The symptoms are an increase in liver enzymes and bilirubin and a yellowing of the skin.

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