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:
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
Acute liver failure
Infection – Viral (hepatitis A, E & B) Seronegative hepatitis Toxic – acute acetaminophen, mushroom poisoning, and other Acute fatty liver(pregnancy, tetracyclines, Reye syndrome) Acute multi-organ(liver) failure following cardiac surgery Ischemic (ligation of hepatic artery, other surgery) Vascular cause(acute Budd Chiari syndrome) Autoimmune hepatitis Drugs – Idiosyncratic – antituberculous drugs Wilson’s disease, Budd-Chiari Syndrome Neonatal hemochromatosis Cryptogenic |
Cirrhosis from chronic liver disease
Infectious – chronic HBV, HCV, HDV liver disease, co-infection (HBV+HIV) Alcoholic liver disease Cryptogenic liver disease |
Cholestatic liver diseases
Primary biliary cirrhosis Primary sclerosing cholangitis Secondary biliary cirrhosis Biliary atresia Alagille syndrome Byler’s disease |
Malignant diseases of the liver
Hepatocellular carcinoma Carcinoid tumor, primary neuroendocrine tumor Islet cell tumor Epithelioid hemangioendothelioma Cholangiocarcinoma* |
Metabolic liver disease
Wilson’s disease Hereditary hemochromatosis Alpha-1 antitrypsin deficiency Glycogen storage disease Cystic fibrosis Glycogen storage disease I and IV Crigler-Najjar syndrome Galactosemia Type 1 hyperoxaluria Familial homozygous hypercholesterolemia Hemophilia A and B |
Vascular diseases of the liver
Budd-Chiari syndrome Veno-occlusive disease |
Miscellaneous
Nonalcoholic fatty liver disease Autoimmune hepatitis (PBC – -overlap syndrome) Chronic drug induced – methotrexate etc Adult polycystic liver disease Nodular regenerative hyperplasia Caroli’s disease Severe graft-versus-host disease Amyloidosis Sarcoidosis Hepatic trauma |
Variant Syndromes
Intractable ascites/ Hepatic hydrothorax Spontaneous bacterial peritonitis Hepatorenal Syndrome Hepatopulmonary Syndrome Chronic encephalopathy Intractable pruritus/ Recurrent cholangitis Unresponsive variceal bleed |
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
Absolute contraindications
Severe cardiopulmonary disease Severe HPS Severe pulmonary fibrosis Oxygen dependent COPD Symptomatic coronary artery disease Severe ventricular dysfunction Advanced cardiomyopathy Severe valvular heart disease and aortic stenosis Extrahepatic malignancy Active alcohol/substance abuse Acute alcoholic hepatitis Active infection/uncontrolled sepsis Lack of psychosocial support Brain dead |
Relative contraindications
Reversible pulmonary conditions Reactive airway disease Hepatic hydrothorax Muscle wasting and infection Advanced age Morbid obesity Acquired immune deficiency syndrome Cholangiocarcinoma Diffuse portal vein thrombosis Previous abdominal surgery Retransplant for HCV infection |
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.
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.
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
Treatment to be offered before transplantation
Modification of immunosuppression post transplant
Requirement of dialysis intra-operatively
Blood culture, urine culture, ascitic fluid cell count, Grams stain, Fungal smear and culture.
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 2nd or 3rd day. Most of the medications are stopped by 3-4 days. Operatively placed tube drain is removed by 3rd or 4th day depending upon the amount and kind of drainage. By 5th or 6th 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 5th 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:
In Wards
Medication
Medication Schedules
Diet and nutrition
Food to be avoided
Personal hygiene:
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,
Exercises
Dental care:
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:
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.
Why is it possible –
Why we need LDLT? (in Nutshell)
* Organ retrieval and banking organzation-AIIMS
Principle of Living donor liver transplant
Double Equipoise: “Balances between donor risk and recipient benefit”
Living donor liver transplant: Who can become a living donor? (Requirements)
Living donor liver transplant versus deceased (cadaveric) liver transplant
Liver transplantation (LT) is the best treatment for patients with end-stage liver disease (cirrhosis). Living donor LT (LDLT) has developed as an alternative to deceased donor LT (DDLT) in order to overcome the critical shortage of deceased organ donations, particularly in India (Asia). The retrospective A2ALL cohort study concluded that graft survival did not differ significantly for recipients of LDLT compared with DDLT once centres have sufficient experience with LDLT. LDLT can shorten the waiting time and lower the dropout rate (hepatocellular cancer). One meta‐analyses revealed comparable patient survival rates and no significant differences in the recurrence rates between LDLT and DDLT recipients. Another meta‐analysis provided evidence of lower disease‐free survival (DFS) after LDLT compared with DDLT for HCC. In 2014, meta-analysis concluded that biliary complications, vascular complications, and retransplantation occur more frequently in LDLT recipients because of its technical complexity, but the biliary complication rate appears to decrease dramatically as a centre gains greater LDLT experience. Recent retrospective review revealed superior survival rates in LDLT compared to DDLT. The study also concluded comparable biliary/vascular complications and early reoperation rate in both the groups. Hospital cost were also 30% lower in LDLT group. Various preoperative optimisations including nutritional treatment can also be planned for both the donor and recipient in LDLT. Unfavourable characteristic associated with LDLT includes donor risk. Donor morbidity is not uncommon and the donor mortality rate is around 0.1–0.3%. Hence the principle of double equipoise in LDLT, which balances the donor risk and recipient benefits. LDLT means recipient receive partial graft (65%-70% of the whole liver) , hence it may not meet the metabolic demands of a very huge or a very sick patient. However liver has the ability to regenerate to meet the metabolic demands of the given recipient. Since the organs in LDLT scenario are private property, rules of listing applicable for DDLT recipients doesn’t apply. Hence the waiting period is not only minimised it helps optimisation of recipients too which translates into improved outcomes. DDLT on the other hand has certain set of rules (listing criteria) to be followed for example the HCC recipient needs to be within predefined criteria ( MILAN criteria), minimum required MELD criteria and certain types decompensation ( hepatic encephalopathy, hepato-pulmonary syndrome etc). Quality of organs cannot be controlled in DDLT scenario, however in LDLT that is a viable option. Overall from the available experience and evidence it can be safely concluded that both the options are equally good and share its own set of problem. However from patient perspective early transplant can improve outcomes and reduce the cost of treatment.