A piece of liver is removed from a living donor and transplanted into a recipient to replace their own diseased liver.

 

Liver transplantation: is the replacement of a diseased liver with a healthy liver allograft. The technique used is orthotopic liver transplantation, in which the patient’s own liver is removed and replaced by the donor organ in the same anatomic position as the original liver. Auxiliary partial orthotopic liver transplantation (APOLT) is also performed in certain cases of acute liver failure and some metabolic liver diseases. Liver transplantation nowadays is a well-accepted treatment option for end-stage liver disease, acute liver failure and liver cancer (hepatocellular carcinoma or HCC).

 

Recipient Selection Criteria:

By and large indications for liver transplant are based on the following principals;

1. Complications of end stage liver disease;
2. Recurrent episodes of variceal hemorrhage (blood vomiting or black stools)
3. Diuretic resistant ascites (water in the tummy)

• Recurrent attacks of hepatic encephalopathy (attacks of drowsiness or coma)

1. Spontaneous bacterial peritonitis (infection in the belly water)
2. Hepato-pulmonary syndrome
3. Porto-pulmonary syndrome

1. Oncological (Cancer in the liver)
2. In this group the predominant indication is liver cancer (hepatocellular carcinoma or HCC)
3. Selective patients with neuroendocrine (carcinoid tumors) liver metastasis and highly selective cases of hilar cholangiocarcinma (cancer of the bile ducts) can also be considered for liver transplantation.

• Hepatoblastoma (liver cancer in children)

1. Quality of life issue

In certain diseases of the liver (in few cases of primary biliary cirrhosis, primary sclerosing cholangitis and familial amyloid polyneuropathy) where there is no imminent threat to life but the quality of life is very miserable, liver transplant is considered as treatment to improve quality of life.

1. Acute liver failure

Fulfilling King’s College hospital Criteria

1. Acute on chronic liver failure

Patients are assessed by following criteria:

1. Child-Pugh-Turcott score (class B and C. Class A patient can be considered if they have developed hepatocellular carcinoma)
2. MELD score (meld score of 15; patient with meld score < 15 can be considered if they have clear clinical indications not reflected by the meld score).

1. Other etiologies:
2. Viral hepatitis (Hepatitis B & C), alcoholic liver disease & metabolic liver disease (Nonalcoholic Steatohepatitis or NASH).
3. Autoimmune liver disease including Primary biliary atresia, Primary sclerosing cholangitis, neonatal sclerosing cholangitis, biliary atresia, Caroli’s disease, TPN-induced cholestasis.

• Genetic liver disease including hemochromatosis, Wilson’s disease, Alpha-1 antitrypsin deficiency, Glycogen storage disease (type-I, III, IV), Tyrosinemia, Criggler-Najjar syndrome, primary Hyperoxaluria.

1. Vascular liver disease (e.g, Budd-Chiari syndrome).
2. Hepatocellular Carcinoma (HCC) confined to the liver with no obvious vascular invasion.

Recipient Exclusion Criteria (contraindications to transplant):

1. Severe, irreversible, medical illness that limits short term life expectancy
2. Severe Pulmonary Hypertension (Mean PA pressure > 50mmHg)
3. Cancer that has spread outside of the liver
4. Sepsis or uncontrollable infection
5. Active substance abuse (Drugs and/or Alcohol)
6. History of non-compliance, or inability to adhere to a strict medical regimen
7. Severe, uncontrolled Psychiatric illness
8. Uncorrectable congenital abnormalities which are severe and life threatening

Relative Exclusion Criteria:

1. Advanced malnutrition
2. Active Infection
3. Inability to understand the risk/benefits of the procedure
4. Inability to comply with medications and conform to follow up regimens

 

 

 

 

Structure & functioning of the liver transplant team:

 

The liver transplant team is a group of different health care professionals working in a multidisciplinary team, and are responsible for all aspects of care of patients suffering from liver diseases.  The aim of the liver transplant team is to practice evidence based medicine at the highest possible international standards.

 

The liver transplant Multidisciplinary team:

1. Surgeons
2. Physicians
3. Anesthetists
4. Intensivists
5. Transplant coordinators
6. Nurses
7. Dietician
8. Pharmacists

The Assessment Process

It is a stepwise assessment of the recipient and the donor. The purpose of stepwise assessment is to avoid un-necessary investigations. Assessment starts from recipient once he/ she has clear indications of liver transplantation.

 

Objectives of liver transplant assessment:

1. Right recipient selection
2. Right donor selection
3. Better outcome

 

Stepwise Recipient Assessment:

Patients are examined by hepatologists and liver transplant surgeons. After initial assessment if a patient is a candidate for liver transplant, detailed briefings are given to the patient and their family regarding the risks and benefits of the transplant operation.

Patients are given time to think and plan transplantation. They are also provided with educational material. Once the patient has made final decision for liver transplantation, the detailed assessment process is started that includes following:

 

Radiological assessment 

1. Ultrasound of the abdomen
2. Liver dynamic CT abdomen, and Chest CT to rule out/stage HCC, determine extent of liver disease
3. MRI and CT brain in selected cases

Cardiac Assessment:

1. ECG
2. Echocardiogram/stress echo including PA pressure
3. Coronary angiogram (selected cases )
4. Cardiologist comments

 

Pulmonology assessment

1. CXR
2. Pulmonary function tests
3. Pulmonologist evaluation

 

Nephrology assessment

1. Renal function tests
2. Routine urine analysis
3. Urine culture
4. Nephrologists evaluation

Psychiatry assessment

1. Consultation & Evaluation

 

Mammography and Gynecological consultation in selected cases

 

Laboratory work-up of Recipient:

 

	Hematology				Serology
			CBC (Differential)					Hepatitis B Profile (HBsAg, HBcAb, HBsAb)
			PT/INR					Hepatitis Be Antigen
			APTT					Hepatitis Be Antibody
			ABO Blood grouping					HBV DNA  (Quantitative)
			Fibrinogen level					Hepatitis C Virus Antibody (HCV)
			Sickle cell screen					HCV RNA By PCR  (Qualitative)
						HCV RNA By PCR   (Quantitative)
		Coomb’s Test Direct				HCV- Genotype
		Coomb’s Test Indirect				Hepatitis Delta Antibody
		Reticulocyte count				HIV 1 & 2 screening (Antigen & Antibody)
		Anti Thrombin III		Autoantibodies
Tumor Markers							ANA Group (ANA, AMA, ASMA)
		Alpha Feto-protein				ANCA
		CEA				Anti LKM 1
		CA-125				Anti-Ds-DNA
		CA-19-9				Rheumatoid Factor
		PSA				Lupus Anti Coagulants
		LDH				Anticardiolipin Antibodies (IgG)
						Haptoglobin
Immunoglobulins
		Immunoglobulin  (IgA)		Virology
		Immunoglobulin (IgG)							CMV Serology IgG
		Immunoglobulin  (IgM)							CMV Serology IgM
Biochemistry									Toxoplasma    IgG
		Chem 7							VZV IgG (Herpes IgG)
		Calcium							EBV IgG
		Phosphorus		Microbiology
		Serum Iron							Blood C/S
		TIBC							MRSA Swab (Nasal & Throat)
		Hb A1 C							Urine R/E
		Serum uric acid							Urine C/S
		Serum Copper							Creatinine Clearance
		Ceruloplusmin							Urine Protein (24H)
		Serum Ferritin							Urine Creatinine (Spot)
		LFTs							Urine Sodium  (Spot)
		Gamma GT							Urine Potassium (Spot)

			Serum Albumin		Radiology
		Thyroid Profile (T3, T4, TSH)				CXR One View
		Lipid Profile (Fasting)				USS Doppler Liver
		Alpha one Anti-Trypsin levels				Liver Dynamic CT scan / CT Chest with contrast
		Magnesium		Endoscopy
		Homocysteine				EGD
Pulmonology				Cardiology
		Pulmonary function test				ECG
		Arterial blood gases				ECHO-2D with pulmonary pressure readings
						Stress test (only for smokers & Positive family History of IHD Coronary Angiography (if positive ischemia as above)

 

Stepwise donor evaluation:

Once it is assured that patient is fulfilling the liver transplant criteria and is fit enough to undergo major surgery, the donor workup starts. We accept donors from within the family (close blood relatives and non-close blood relatives) according to the following criteria:

 

Living Donor selection criteria:

 

• A blood related person or a spouse who shares compatible blood group with the patient.
• Donors must be healthy individuals with no major health problem.
• Must be in good physical and mental health
• Must be between the ages of 18 and 50 years
• Voluntarily, altruistic donation
• Have a body mass index (BMI) less than 35
• Must have a compatible blood type with the recipient
• Must be free from the following:
  • Significant organ diseases (i.e., Heart, Lung & Kidney disease, etc.)
  • Ongoing malignancy (cancer)
  • HIV/AIDS
  • Hepatitis
  • Active or chronic infections
  • Active substance abuse

Laboratory work-up the living donor:

 

Special Considerations and/or Issues in Donor Evaluation:

Donor Advocate:

Usually a physician outside of the transplant team, who will help the donor understand the process, procedure, risks and benefits of live organ donation.  The donor advocate will protect and promote the interests and well-being of the donor. Donors can opt to withdraw at any time during the assessment process.  The reasons for withdrawal will be kept confidential.

Liver Biopsy:

Our program may perform liver biopsy on potential donors based on clinical findings that suggest some degree of concern regarding histological status of the liver, i.e., elevated AST/ALT, presence of steatosis on imaging studies and so on.

 

Cost of Donor Evaluation:

Financial considerations of the donor evaluation and hepatectomy are important to consider because the process is complex and expensive and some of donors has “failed donor evaluations,” i.e., potential donors who undergo testing and are rejected for donation. Living donation is not possible for all the donors due to medical and technical reasons.

The purpose of the stepwise evaluation of the donor is to avoid un-necessary investigations. If the donor is found to be unsuitable at any step, the other investigations should be abandoned. Before starting the investigations of the donor, detailed history and physical examination including height, weight, BMI is recorded. Steps of donor evaluation are as follows:

Step I

S #		Work Up
1		Abo Grouping
2		CBC Diff
3		PT (Prothrombin Time)/INR
4		LFT, s
5		Urea
6		Glucose Random
7		Albumin
8		Creatinine
9		Magnesium
10		Electrolytes (Na+, K+, Chlor, Bicarb)
11		Urine R/E
12		Hepatitis C Virus Ab (HCV)
13		Hepatitis B Profile (HbsAg, HBC Ab, Hbs Ab)
14		HIV 1 & 2 screening (Antigen & Antibody)
Radiology
15		CXR One View (PA-View)
Cardiology
16		ECG

Step-II
		Liver Dynamic CT Scan
		ECHO-2D With pulmonary pressure readings

	Step-III
					MRCP
	Blood Investigation
	Thrombotic Screen
	2				Lupus anti-coagulant
	3				Anti-thrombin III
	4				Protein S
	5				Protein C
	6				APC
	7				Anti Cardiolipin IgG
	8				Resistance V (Factor V)
	Bio Chemistry
	9				G6PD (Qualitative)
	10				Reticulocyte count
	11				Sickle cell
	12				HbA1C
	13				Full lipid profile
	14				Thyroid function tests
	15				Serum Ferritin
	16				Serum copper
	17				Ceruloplasmin
	18				Alpha one anti-trypsin
	Immunology Screening
	19				Immunoglobulin  (IgA)
	20				Immunoglobulin  (IgG)
	21				Immunoglobulin  (IgM)
	22				ANCA
	23				ANA Group (ANA, ASMA, AMA)
	24				Type Antibody Screen
	25				Comb’s Test Direct
	26				Comb’s Test Indirect
	27				CMV Serology IgG
	28				Toxoplasma    IgG
	29				EBV IgG
	30				MRSA Swab (nose, throat and Skin Scraping)
	31				VZV (Herpes) IgG
Radiology
1				MRI abdomen with contrast
2				USS Doppler abdomen (Hepatic & Portal Vein)
Consultations
1		Step –I		Transplant Surgeon
2		Step-II		Hepatologist
3		Step-III		Psychiatrist
4		Step-IV		Anesthetist
5		Step-V		Donor Advocate
6		Step VI		Presented to Hospital ethical committee  & approval from Human Organ Transplant Authority (HOTA)

 

After complete assessment of the recipient and the donor, the case is presented in Transplant Multidisciplinary Meeting (MDM).

Transplant Multidisciplinary Meeting (MDM) Guidelines:

 

1. a) Objective: Discussion of all patients under consideration for transplantation.

Attendees:

1. Consultant Hepatologist
2. Consultant Liver Transplant Surgeon(s)
3. Consultant Liver Transplant Anesthetist(s)
4. Consultant Intensivist(s)
5. Transplant Coordinator Team (including MDT Co-ordinator). The Co-ordinator will also act as a social worker
6. Physicians in training
7. Nurses responsible for care of patient

1. b) Agenda in brief: For each patient:
   1. Short/salient summary of each patient based on evaluation proforma and listing meeting outcome.
   2. Discuss suitability for transplantation
   3. Discuss necessity/appropriateness of further investigations
   4. Define action plan (outcome) – listing/ time-frame – record outcome – Database

 

1. c) Presentation at MDM: List of all patients for discussion to be circulated to attendees 24hrs prior to meeting (responsibility of MDT Co-ordinator). All names are forwarded 24 hours before the meeting.

Give short summary of patient’s history: indications for transplantation, presentation, referral source, suspected/confirmed diagnoses, and investigations +/- treatments to date.  Summarise all available relevant transplant assessment related investigations.

1. d) Discussion:

• Rationalisation for transplantation and absolute/relative contraindications:
• Exploration of other treatment options/further investigations
• Recommendation of treatment(s) (e.g. abstinence programs etc)

1. e) Define action plan:

• If accepted for listing, discuss priority/type of graft/immunosuppressant regimen.
• If not listed, define reasons/future candidacy/ follow up plan.
• If patient to be re-discussed, define issues for re-discussion
• Record outcome – with review date if appropriate

 

1. f) Updates: Updates will only be discussed on the basis that they require a new decision from the Transplant MDM.

1. g) Acute Liver Failure: Patients with acute liver failure approaching or meeting listing criteria for urgent transplantation can be discussed ad-hoc and listed upon agreement between Intensivist/Hepatologist/consultant transplant surgeons. We follow King’s College criteria for liver transplant in acute liver failure.

 

1. e) MDM- Responsibilities of Transplant Co-ordinator:

• Preparation of MDM
• Circulate list to all attendees 24hrs prior to the meeting
• Record attendance and generate quarterly report for “Chair”
• Ensure outcomes are recorded – check database & written record
• Contribute to MDM discussion – additional information including influential factors e.g. social issues, previous experience of patient

After approval from transplant MDM both the donor and the recipient are presented to the hospital Evaluation Committee for final approval. Hospital evaluation committee is a legal requirement of Human Organs and Tissues Act, 2009 (No.F.9 (1)/2009-Legis).

1. g) The Hospital Evaluation Committee:
2. Ensures that no organ or tissue is retrieved from non-related living donors without the prior approval of the Evaluation Committee
3. Determine propriety of removal of a human organ from any living person using brain death protocol to be formulated; and

• Determine fitness or otherwise for transplantation of a human organ into any other body.

The hospital Evaluation Committee either approves the case (for close blood relatives) or forwards it to Human Organ Tissue Authority (for non-close blood relatives).

Documentary evidence of relation is established by relevant national identity card, birth certificate and marriage certificate.

In case of non-close blood relatives the evaluation committee evaluate for the following:

1. There is no commercial transaction between the recipient and the donor. No payment of money or money’s worth as referred to in HOTA act, has been made to the donor or promised to be made to the donor or any other person. In this connection, the Evaluation Committee shall take into consideration:

1. An explanation of the link between recipient and donor and the circumstances which led to the offer being made.
2. Documentary evidence of the link e.g. proof of relationship (NADRA Family Relationship Certificate-FRC).
3. Reason why the donor wishes to donate.
4. There is no middleman / tout involved.

• The donor is not a drug addict or active substance abuse

1. The next of kin of the proposed donor gives permission on stamp paper in case of non-close blood relatives.

SURGICAL PLANNING

After assessment of the recipient and the donor the surgical team designs surgical plan

For the living donor liver transplantation.

After this process is complete, both the recipient and the donor are informed about the process of liver transplantation in detail and informed consent is obtained separately from the donor and the recipient and the date of surgery is decided and following plan is given all the risks and benefits of the transplant to the donor and to the recipient are explained in detail. Recipient, donor and the family is provided with the opportunity to enquire any other information regarding the whole process.

The recipient operation will take 8-12 hours. The recipient will stay 4-6 days in the ICU followed by another 2 weeks in the hospital. The recipient average hospital stay should be around 12-15 days. Donor’s total hospital stay should be 7-8 days. The recipient will be given prophylactic antibiotics, analgesia, low molecular weight heparin for DVT prophylaxis and immunosuppressive drugs (including Tacrolimus, Mycophenolate Mofetil and steroids), anti-fungal medication and Omeprazole.

Liver transplant co-coordinator will accompany the patient and their family throughout the process to facilitate them at each and every step.