Liver has tremendous capacity to compensate for any insult sustained and it is only when the liver decompensates that one comes to know about the liver disease. Because of the enormous reserve the liver has, by the time patient presents to the clinician, there is some form of decompensation and the liver might have sustained sufficient damage and the liver functions would be deranged. Decompensation can be in the form of:

1. Collection of fluid inside the tummy (otherwise termed as ascites)
2. Development of jaundice
3. Disturbance in the sleep pattern, excessive somnolence, drowsiness and coma (hepatic encephalopathy)
4. Blood in the vomitus or passing black colored stools (variceal bleed).

Other problems which occurs in patients with chronic liver disease are the hepatorenal syndrome (HRS, renal dysfunction) and infection in the ascitic fluid (spontaneous bacterial peritonitis-SBP), both of which increases the risk of dying at the end of one year in these patients to >50%.

Liver transplantation is indicated in patients suffering from end stage liver disease of varying etiology, acute liver failure fulfilling criteria for emergency liver transplant, malignancy of the liver even if the liver functions are relatively preserved, in metabolic liver disease where there is congenital abnormality leading to deficient liver functions, where a liver transplant is curative, and there are various other miscellaneous indications. 

Listing criteria

There are various scoring systems which have been used for listing patients for liver transplant. These are basically useful to stratify these patients so that one can predict the risk of mortality without transplantation. The Child Turcotte Pugh score (CTP score – Table 1) of ≥7 and the Model for End Stage Liver Disease ≥10 (MELD – Table 2) or the Pediatric End Stage Liver Disease ≥10 (PELD – Table 2), are the minimal listing criteria for liver transplantation. To get listed for transplant the risk of mortality without transplant should be ≥ 10% within one year. Liver transplant hence should lead to increased survival and a better quality of life. 

Indications – Table 3

Table 3 – Indications for liver transplant

Apart from the cirrhotic patients with decompensated liver disease with the above mentioned scores, there are other problems related to chronic liver disease which form an indication for liver transplant. These are the variant syndromes in the form of hepatorenal syndrome (kidney functions get deranged because of liver disease), hepatopulmonary syndrome (HPS-oxygenation suffers because of liver disease), portopulmonary hypertension (PPS-heart gets affected because of liver disease), intractable ascites (fluid in the tummy not amenable to medical treatment), intractable variceal bleed (blood in the vomitus or stool not responding to medical or endoscopic treatment), hepatocellular carcinoma (HCC-liver cancer), quality of life issues (recurrent cholangitis, intractable pruritus because of high jaundice), and chronic encephalopathy (deranged level of consciousness because of liver disease).

In children, the most common reason for needing a liver transplant is biliary atresia. In biliary atresia, the bile ducts are missing, damaged or blocked. The bile ducts are tubes that carry bile from the liver to the gallbladder and small intestine. When they are blocked, bile backs up in the liver and causes cirrhosis.

Patients who present with acute liver failure (ALF-characterised by jaundice, encephalopathy and coagulopathy) of varied etiology and who fulfil the criteria for emergency liver transplant account for nearly 10% of patients needing liver transplant. In the West, acetaminophen toxicity is the leading cause for acute liver failure, other common causes being hepatitis A, E, B and seronegative hepatitis. Idiosyncratic drug toxicity is another cause for fulminant and subfulminant hepatic failure. There are certain validated criteria for emergency liver transplant in these patients and once the patients meet these criteria; there is very short window period for action. Without transplantation there is almost 100% mortality which is either because of liver failure or because of sepsis and multi-organ failure. King’s college criteria (Table 4) is the most commonly followed criteria, apart from which there are other criteria – Wilson’s prognostic index (Table 5), Clichy criteria (Table 6), and UK Blood and Transplant criteria (Table 7). Patients with acute liver failure who meet criteria are placed on the highest priority to receive the deceased donor organ and if the family has a living donor, they are worked up rapidly for an emergency liver transplant.         

Table 3 enumerates the various causes for acute liver failure and chronic liver disease (CLD) which would require liver transplantation. The table also enumerates the indications for liver transplantation which are typically not covered by the standard scoring system (Child Turcotte Pugh score and the MELD/PELD score). They are termed as variant syndromes.

Other criteria which are followed in patients with fulminant hepatic failure are as mentioned in the table 7 and these are for specific cause of acute liver failure.

Patients, who do not have a living donor, are listed for deceased donor liver transplantation (DDLT) and apart from them being listed they are given a status according to the urgency of liver transplantation. This is for better allocation of organs once available. Table 8 details the status and the criteria for the same. This was implemented by the United network for organ-sharing (UNOS) in 1997 and later modified in 1998.

Contraindications – Table 9

Table 9 – Contraindications for liver transplant

The contraindications are the usual absolute contraindications for any major surgery which would include severe cardiopulmonary disease and it also includes other contraindications like the presence of active infection, ongoing alcohol or substance abuse etc. It is very important that the patients with alcoholic liver disease are abstinent before transplantation, this period of abstinence is helpful in two ways: first it ensures that the patient can remain abstinent following transplant so that the compliance is maintained, second many patients might recover with a period of abstinence to an extent that they might not require transplant. There are other relative contraindications which are listed in the table.

It is important that one realises the contraindications for liver transplantation. Patients who are actively consuming alcohol or are having substance abuse are not candidates for transplant, as they have high incidence of recidivism, and non compliance for taking immunosuppressive medication which would ultimately lead to graft (new liver) loss. Advancing age is a relative contraindication as long as they do not have severe cardiopulmonary compromise. Generally 70 years is accepted as cut off limit in many centres.  Morbid obesity is another contraindication as these patients have a high post transplant mortality related to the associated cardiovascular comorbidity.

Once the patient fulfils the above indications and the contraindications are ruled out, then the patient along with the living donor are evaluated for transplantation. This includes a series of tests for the patient and the donor to establish their fitness to undergo transplantation. Evaluation is done by the transplant surgeons, hepatologists, cardiologists, pulmonolgists, anaesthesiologists, and psychiatrists. Patients who do not have a living donor are placed on the deceased donor liver transplant list after their pretransplant evaluation is complete. While on the list these patients are on regular follow-up, to treat any episode of decompensation/infection. This helps in ruling out active infection or any other morbidity which needs treatment before they can be transplanted.

Evaluation of Recipient

Patient with acute liver failure/chronic liver disease for whom liver transplantation is indicated (as stated in other section) is extensively investigated before listing for liver transplantation. As end stage liver disease has adverse effects on other organ systems of the body, a multidisciplinary team (including Hepatologist, Transplant surgeons, Anesthesiologist, Cardiologist, Chest physician, Dental surgeon, Psychiatrist, Gynaecologist for female recipient) evaluates the patient and then he/she is planned for Living donor liver transplantation or is placed on the waiting list for deceased organ.

• Finding out the etiology of Acute liver failure/chronic liver disease

Fulminant – Viral serology specially Hepatitis A, E, and B, Serum Ceruloplasmin for acute Wilsons, history of drug intake in recent past especially anti-tubercular drugs in our country

Chronic- Viral serology for Hepatitis B and C – viral load is done if HCV/HBV positive.

Auto-antibodies, serum Ceruloplasmin, history for alcoholic liver disease is established on the basis of history, history of diabetes, lipid profile, body mass index to rule out non-alcoholic steatohepatitis (NASH) related cirrhosis.

• Haematological and Biochemical evaluation
  1. Complete blood count, Liver function tests:

                 Assessment of the kind of blood products to be arranged for the transplantation,requirement of transfusion before the transplantation procedure etc.

Childs status of the patient is calculated  

1. Renal function helps in decision making:

Treatment to be offered before transplantation

Modification of immunosuppression post transplant

Requirement of dialysis intra-operatively

• Lipid profile, Iron studies, Cytomegalovirus IgG/IgM
• Thyroid profile (many patients with chronic liver disease have hypothyroidism, which would require treatment to be started preoperatively – this avoids problems of weaning off from the mechanical ventilation post-transplantation)
• 24 hours Urine analysis – to study renal reserve and helps in deciding for and against investigating further for the renal reserve in the form of DTPA scan.
• Tumour markers – Alpha-fetoprotein (AFP-for hepatocellular carcinoma), Ca-19-9 (for pancreatic malignancy), CEA (for colorectal carcinoma), PSA (incase of male patients to rule out prostatic carcinoma), Ca-125 (increases in female patients with ovarian malignancy).
• Cultures are done to rule out any infective focus and to treat the same effectively if there is any such focus of infection.

Blood culture, urine culture, ascitic fluid cell count, Grams stain, Fungal smear and culture.

• Imaging

1. Ultrasound of the abdomen with Doppler studies – gives information about any space occupying lesions in the liver, patency of the portal vein, hepatic veins, inferior vena cava and hepatic arteries. Important in patients with Budd Chiari Syndrome (BCS), who have blocked hepatic veins and/or inferior vena cava. Important in patients with portal vein thrombosis (to plan the surgical strategy). If the serum creatinine is good we get the triphasic CT scan of the abdomen done without getting the liver Doppler study.
2. Triphasic-CT scan of the abdomen – This scan gives important information about the liver lesions (hepatocellular cancer, is common in patients with cirrhosis), if any. Also gives information about the portal vein (patency and thrombosis if present characterizes the extent of the same), hepatic vein, inferior vena cava and hepatic arteries.
3. Bone scan and High resolution CT scan of the chest – done in patients who have hepatocellular carcinoma. This is done to rule out any extrahepatic disease which would go against performing a liver transplant.
4. MRI with Venography – reserved for patients with renal dysfunction, this gives similar information as triphasic CT scan.
5. PET scan – is done in patients with hepatocellular carcinoma as a part of tumour work-up to rule out tumour in other parts of the body.

• Other system examination to look for fitness to tolerate the transplantation procedure
  1. Chest physician clearance – requires chest X-ray, pulmonary function test, arterial blood test, following these tests, chest physician gives his opinion and clearance for the transplantation procedure
  2. Cardiology clearance – ECG, echocardiography and stress echocardiography is done, following which clearance is obtained. Specialized tests (contrast echocardiography, macroaggregated albumin scan) are done in specific situations.
  3. Hepatology clearance – Upper gastrointestinal endoscopy is done to look for varices, which if large might require treatment before transplantation in some patients. Clearance is obtained from liver physicians.
  4. Gynaecology clearance – for female recipients, ultrasound of the pelvis, pap smear and mammography/ultrasound of the breast is performed and clearance is obtained.
  5. Dental clearance is taken to rule out any focus of infection before transplantation. It might involve extraction of tooth is there is any evidence of abscess.
  6. Psychiatric clearance is especially important for patients with alcoholic liver disease to look for the period of abstinence and also to assess their willingness for continuing abstinence, this might give an idea about the chances of recidivism.
  7. Anaesthesia clearance is obtained after the above clearances are obtained.
• Authorisation Committee clearance – This clearance is important before doing a living related liver transplant and this is organised by our transplant co-ordinator. Once the donor and recipient evaluation is complete(cardiovascular clearance for both and donor triphasic CT scan with volumes) then the required documents are asked for by our co-ordinator to get the approval by the committee.

Operative procedure

Donor is admitted one day prior to the day of transplantation. Routine blood tests are done (haemogram, liver and renal functions) before the day of surgery.

On the day of surgery, the donor and patient, both are wheeled in two different operation rooms simultaneously.  Both the surgeries start simultaneously (except in patients with hepatocellular carcinoma, where recipient is opened up first to rule out any extra-hepatic spread of tumor before starting the donor surgery).  The part of liver which is planned to be taken as graft is carefully removed, safeguarding the remnant liver in the donor.

Gall bladder is routinely removed at the time of donor hepatectomy surgery irrespective of the type of graft planned- right, left, left lateral or posterior segment graft. This is because the gall bladder blood supply might get compromised and also because the cystic duct is utilized for intra-operative cholangiogram which aids in the transection of the bile duct and thereby reduces/avoids biliary complications in both the donor and the recipient. It is important to note that the gall bladder is just a storage organ for bile, which is actually formed in the liver; hence removal of the gall bladder does not in any way harm the donor. Once the recipient is ready to receive the graft only then the proposed graft is removed and sent for benching in a basin containing ice. After the procedure, wound is closed in the donor carefully (cosmetic sutures which are absorbable-does not require removal) and a tube drain is kept at times to drain any collected fluid. This is generally removed in 3-4 days. The operation generally lasts for 6-8 hours. We also are performing donor surgery with the assistance of laparoscopy. The advantage is smaller incision and less pain, otherwise everything remains the same.

Benching

The graft after resection is flushed with cold preservative solution to remove all the blood. Benching also involves clearing and preparing the vessels and bile ducts for implantation in the patient.

Postoperative care

Generally blood transfusion is not required in this procedure. Donor is extubated (removed from the mechanical ventilator) after surgery in the operation theatre. He/she is shifted to the Intensive care unit for overnight observation. After surgery, donor has a tube in the nose to keep the stomach empty and avoid vomiting immediately after recovery from anaesthesia. This is usually removed on the first postoperative day. Urinary catheters are there for convenience in the initial 2-3 postoperative days, following which as the donor starts ambulating, the catheter is removed. Donor would also have some intravenous lines for giving fluids and medications; these are progressively removed over a period of 4-5 days. For pain relief, epidural analgesia (catheter in the back)/ intravenous analgesia/ local wound block is used, which can be supplemented if required with additional dosage and in combination.

Generally donor is shifted to the ward on the first postoperative day. Diet is started gradually from the first day following surgery and is progressed to normal diet by the 2^nd or 3^rd day. Most of the medications are stopped by 3-4 days. Operatively placed tube drain is removed by 3^rd or 4^th day depending upon the amount and kind of drainage. By 5^th or 6^th postoperative day, if everything is progressing as expected donor is discharged. Liver functions return to normal by 5-6 days following surgery.

At discharge, pain killers, vitamins are prescribed. These are stopped in 3-4 weeks. Operative wound would require dressings for 7-10 days. Donor should avoid strenuous activity and lifting heavy weights for 3-months following surgery. However he/she could resume daily activities and jobs which do not require physical exertion. This surgery leaves a scar across the upper part of abdomen.

Complications

They are minor and can occur in 10-15% of patients in the form of some fluid collection in the abdomen or chest. Like any other surgery there is a chance of bleeding, bile leak, wound infection, which would require attention in some. This would require extra days of stay in the hospital, antibiotics or aspirations under image guidance. Risk to life in this procedure is about ≤ 0.05% for right lobe donation and ≤ 0.02% for left lobe donation.

General Information

Liver transplant operation has good result; however failure to comply with the immuno-suppression medication is the foremost cause of rejection which may lead to organ failure. Close follow up with your transplant team and primary care physician can help ensure a good outcome.  To protect your new liver, it is essential that you and your family members understand the information provided in this guide

After liver transplant operation, the patient will be transferred to Liver Transplant Intensive Care Unit (LICU) which is situated on the 5^th floor next to the OR (operating room) complex. The LICU is manned by experienced staff nurse with 1:1 nursing ratio maintained round the clock. A liver transplant fellow under supervision of a Senior Transplant Consultant provides round the clock cover. The recipient will need to stay in the liver ICU for 4-5 days and the donor for one day.

Complications

As with any other surgery, complications may occur after liver transplant operation. End stage liver disease may affect the functioning of other body systems. It is important for you and your family to be aware of these complications and the risks but it does not necessarily mean that you will experience all or any of them. Some of the major post-operative complications related to liver transplant are enumerated below:

1. Hemorrhage – one of the functions of the liver is to manufacture clotting factors. When a liver fails, the ability to produce clotting factors is impaired. To correct this problem, you’ll receive blood products before and after surgery. It is expected that your new liver will start working very quickly to help prevent any excessive bleeding, but you may have to be re-operated if the bleeding is excessive. The transplant team doctors will keep the family informed accordingly.
2. Thrombosis – A blood clot in the vessels (hepatic artery, portal vein and hepatic veins) leading to or from your liver may injure your new liver. This is a serious complication which might require reoperation for removal of the clot, in some instance a second transplant might be required. A protocol ultrasound Doppler will be routinely performed for first 5 days to diagnose this problem early.
3. Rejection – the body’s immune system protects you from infection. Unfortunately, it also views your new liver as foreign and will try to reject it. To prevent this, you will be started on medication (immunosuppressants) for the rest of your life. Rejection can be diagnosed early by performing regular blood tests and doing liver biopsies (where indicated, it is a needle biopsy under ultra-sound guidance and local anesthesia to retrieve small piece of your new liver to be viewed under microscope). Although rejection is not uncommon, with early diagnosis and treatment the situation can be controlled in most of the cases.
4. Infection – Medications you take for rejection also impair your body’s ability to fight infections. Preventive treatment for infection is given in the initial 3 months during which time the dose of immunosuppressants are high and the drug levels are being monitored. During this period one needs to observe certain precautions like hand washing, wearing a mask, head cap, clean clothes, avoiding crowded and polluted areas, and avoiding contact with people having infection.
5. Respiratory (lung) infection may develop which would keep you in ICU longer on the breathing machine until you are able to breathe normally.
6. Renal (Kidney) dysfunction – Reversible kidney damage may occur especially if the patient had kidney dysfunction before the transplant operation. However, the kidneys gradually recover in most, but very rarely dialysis may be necessary.
7. Medication Side-effects – Immunosuppressive medications prevent and treat rejection. These drugs decrease your body’s resistance to foreign bodies, such as your new liver. You MUST take these medications for the rest of your life to prevent rejection. Immediately after surgery, the dosage will be high since the chance of rejection is greatest at this time and also because the drug level is stabilized. Medications have side effects that are usually dose-related. Most people experience the highest level of side effects in the beginning when dosages are high. High blood pressure, high blood sugar, increased levels of potassium, seizures, tremors, development of cataract etc are few of the side effects. Side effects may occur in some patients and not in others.

In Wards

1. During your stay in wards, you should follow the advice and guidance of the medical and nursing staff.
2. Support and encouragement from family and friends will contribute to patient’s recovery
3. You will have blood sampling every day/as and when required
4. It is common and expected to experience some mild pain and discomfort after the surgery. In case of severe pain, you can request the nursing staff for oral/intravenous medication for pain control.

Medication

1. Do not change or discontinue the medications prescribed by the Liver Transplant Team on your own.
2. Do not take any other medication. If other doctors prescribe any medication, please inform the liver transplant team.
3. Upon discharge you will get a discharge summary detailing all the medicines you need to take. It will also include the timing of these medications.
4. You will also get a blank blood investigation chart and diabetic control follow-up sheet. Our nursing staff will explain how to fill up these forms.
5. Please keep the investigation chart and medication record updated regularly.

Medication Schedules

1. OD – Once a day(in every 24 hrs gap)
2. BD – Twice a day(in every 12 hrs gap)
3. TDS – Thrice a day(in every 8 hrs gap)
4. QID – Four times a day(in every 6 hrs gap)
5. A/D – Every alternate day
6. SOS (Save our soul) – Whenever needed

Diet and nutrition

1. Small and frequent meals preferably high protein content specially during the early post transplant period are advisable
2. Have plenty of fresh fruits and vegetables, which are thoroughly washed and cooked to increase fiber intake.
3. Stick to light foods. Avoid fried or greasy foods.
4. Wash utensils before use.
5. Drink filtered and boiled water only.
6. Do not take food that has been left over night.
7. Include 2 L of fluid (milk, fruit juices, vegetable juices) as it flushes out waste products from the body though during the early part after transplantation you may be advised to restrict fruit/ fruit juices, as these are rich source of Potassium and you may have imbalance of it in the initial post transplant period.
8. Avoid alcohol as it damages the liver
9. Avoid food containing raw egg or mayonnaise. Avoid partially cooked egg.
10. Include food rich in calcium like skimmed milk cheese, Soya, egg, chicken, fish, green-leafy vegetables.

Food to be avoided

1. Expired, partly-cooked and rotten meat and eggs
2. Cold meat
3. Overripe fruits.
4. Fruits that increase potassium levels (banana, coconut water, fruit juices/pulp in a preservative)
5. Unboiled tap water and unfrozen overnight soup.

Personal hygiene:

1. Clean your body with a wet towel and wear washed clothes.
2. Once the wound heals and bags are removed you can take a normal bath before dressing is changed.
3. Once staples are removed, keep the incision dry and clean.
4. If the incision oozes fluid, contact the doctors immediately.
5. Dressing needs to be changed on alternate day

Insulin Regime

Prior to your discharge from hospital, it is advisable that you as well as someone from your family (or any care giver), are proficient in checking the blood sugars at the designated time of the day. They should also learn to administer insulin. The sugar levels as well as the units of insulin given needs to be maintained in a sugar chart; which will be provided to you at the time of discharge. .

You have to check blood sugar levels 4 times in day/or as instructed at the time of discharge,

1. Before breakfast(7am)
2. Before lunch(12pm)
3. Before dinner(7pm)
4. Post Dinner(2hrs after dinner)(9pm)
5. Insulin should be given only after recording the blood glucose level and meal is to be taken after that.
6. If you find that blood sugar is below 100 then please do not give insulin, however regular meal can be taken.
7. If sugar is < 60 then patient can be given glucose biscuits, glucon-D, sugar etc.

Exercises

1. Please do deep breathing exercises as it helps your lungs to expand and enables you to cough up sputum easily. Incentive spirometer will be kept at your bedside and you will have to do the exercises every hourly or as frequently as possible.
2. Take adequate rest and sleep.
3. Weakness in the muscles all over your body and leg muscles in particular, is a result of a lack of exercise after surgery and a side effect of steroid hormones. To strengthen the leg muscles, you are recommended to progressively increase the level of exercises/activity.
4. The physiotherapist will visit you twice a day in the wards and teach you how to exercise your limbs, so that your limb muscles are strengthened, blood circulation is increased and the risk of complication like clots in the blood vessels is reduced. You need to continue doing exercise at home as well.
5. After 3 months you can do almost all exercises like sit-ups, abdominal exercises and swimming etc.

Dental care:

1. Maintain your oral hygiene
2. Always rinse your mouth after eating.
3. If you receive dental care or dental treatment, please let the dentist know that you are a liver transplant patient and that you are on immunosuppressive medication.

Liver transplant operation offers good quality of life. Patients have to visit hospital at intervals and take immunosuppressants lifelong. You will have to come to us twice weekly for first 2-3 weeks followed by weekly visits for a period of further 2-3 weeks. Thereafter the visits will be less frequent and can be fortnightly or monthly based on your clinical condition, lab reports (liver function tests) and drug levels. This is best left to your treating physician’s discretion.  You can do physical activities as a normal person can do, after 3 months. Liver has remarkable ability to regenerate and is usually restored to its original size in approximately 12 weeks.

Danger Signs

You should immediately consult your transplant doctor if you develop any of the following symptoms:

• Fever of 100.5 or greater,
• Shortness of breath,
• Cough that produces a yellowish or greenish mucous discharge,
• Prolonged nausea,
• Vomiting or diarrhoea,
• Persistent or worsening pain,
• Drainage, redness or swelling at the incision site,

 Avoid smoking: Smoking damages the lungs, putting you at greater risk for lung infections, including bronchitis, emphysema, and pneumonia. It also increases your risk of developing cancer. 

Driving: You should speak with your doctor before driving for the first time after your transplant. You will not be able to drive for approximately 3 months after your transplant.

Sexual activity: It is common for transplant recipients to resume a more normal lifestyle, including sexual activity, as they recover. Your doctor is your best guide.

Family and Pregnancy: Some people want to start a family once they have had a transplant and have recovered. However we recommend waiting for a period of 2 years following liver transplant.