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Flashcards in Hepatology - Liver transplantation Deck (18):
1

What are the most common sources of liver for transplantation?

Majority of livers in the UK come from cadavers, but can more rarely be a partial live donor transplant. Live donor transplants are fairly recent to the UK and involve transplanting half of a liver, which increases the risk of mortality to the donor (0.8%)

2

What are the indications for liver transplantation?

Transplantation is indicated in (i) liver failure, (ii) surgical gene therapy and (iii) misc conditions.

(i) Liver failure - further divided into:
a) Acute/ subacute - drug induced, hepatitis, Budd-Chiari, metabolic (e.g. Wilson's)
b) Chronic - alcohol related liver disease, chronic hep B or C, malignancy, NASH, autoimmune hepatitis, other causes of cirrhosis (e.g. PBC, PSC, haemochromotosis)

(ii) Single gene therapy:
- primary oxalosis
- familial amyloidosis

(iii) Misc:
- polycystic liver
- recurrent cholangitis
- hepatopulmonary syndrome

3

How should patients be assessed for suitability for liver transplant?

Transplants are offered at ANY age (although there is worse outcome for those aged >65).

Assess risk of death from liver disease using risk stratification score - e.g. Model for End stage Liver Disease (MELD). MELD score + low serum Na provide good evidence of outcome following transplantation.

Other factors such as resistant ascites need to be taken into consideration.

For "super urgent" cases, the decision has to be made in a matter of days, Kings College criteria often used.

4

What complications are associated with liver disease?

These can be divided into immediate, early and late.

1) Immediate - bleeding, poor graft function
2) Early - sepsis, vascular anastomoses problems, biliary anastomoses problems, acute graft rejection, immunosuppressive toxicity
3) Late - immunosuppressive consequences (e.g. bone marrow suppression), disease recurrence, chronic graft rejection (rare)

Many centres give short term antibiotics and prophylactic anti-virals. Other drugs may also be given prophylactically, e.g. co-trimoxazole for pneumocystis and fluconazole for fungal sepsis

5

What immunosuppressive medication are patients placed on post transplantation?

Combination of drugs are used consisting of a calcineurin inhibitor, steroids (weaned after 6 weeks unless there is concomittant hepatitis C) and azothioprine. Subsequent immumosuppression may be tacrolimus or ciclosporin alone, or duel therapy with either azothioprine or mycophenolate. Tacrolimus may be superior to ciclosporin but patients are at an increased risk of diabetes mellitus.

6

How does transplant rejection usually present?

Acute rejection usually presents with raised liver enzymes, bilirubin and eosinophilia, and may be asymptomatic. Patients who are symptomatic usually experience nonspecific symptoms - eg, lethargy, fever and abdominal pain. On the other hand, chronic rejection usually occurs after one year and is referred to as the 'vanishing bile duct syndrome'. Again, patients may have abnormal liver function (hepatitic or cholestatic picture), nonspecific symptoms or jaundice with pruritus.

7

Outline the approach to a liver transplant patient who presents with an acute illness

Always think of sepsis and remember the patient is immunosuppressed - eg, chest, urine, atypical site (sinuses or brain as examples), abdominal.
Consider whether they are dehydrated. Renal impairment is common and may lead to potential drug toxicity.
Consider adverse drug interactions.
If acutely unwell - contact the local transplant unit or organise admission urgently.

8

How should you manage a liver transplant patient who presents with chronic illness?

Still consider infection, especially as the patient will not be able to mount signs and symptoms as an immunocompetent individual.
Consider adverse drug interactions.
Organise routine blood tests - eg, FBC, U&E, LFT.
Request drug levels (blood samples need to be taken before early morning dose).
If you think chronic rejection is the cause, then discuss this with liver team at the next available opportunity.

9

What routine checks should be done in a liver transplant patient?

1) FBC, U&E, LFT
2) Monitoring drug levels
3) Metabolic and cardiovascular risk - fasting lipids and glucose, BP, weight gain
4) Cardiovascular risk reduction - 20% of liver transplant deaths are related to cardiovascular disease
- reduction involves lifestyle modification and drugs, e.g. statin (pravastatin is preferred), ACEi and CCBs
5) Monitor ethanol intake
6) Smoking cessation
7) Cancer surveillance
8) Osteoporosis screen
9) Vaccination - avoid live vaccines

10

What is the prognosis following liver transplantation?

Five-year mortality is highest for patients who received a transplant for malignancy, second highest for acute liver failure and hepatitis C and lowest for primary biliary cirrhosis. Disease recurrence can occur and will reduce the prognosis - eg, viral hepatitis (especially hepatitis C), autoimmune hepatitis and primary biliary cirrhosis. Immunosuppressive therapy can also impact on prognosis; for example, 10-20% will develop calcineurin inhibitor-related renal impairment five years after transplant.

11

What group of patients are at increased risk of developing hepatotoxicity following paracetamol overdose?

Patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort)
Malnourished patients (e.g. anorexia or bulimia, cystic fibrosis, hepatitis C, alcoholism, HIV
Patients who have not eaten for a few days

12

When should NAC be given in paracetamol overdose?

Acetylcysteine should be given if:
- there is a staggered overdose (if all the tablets were not taken within 1 hour) or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or
- the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity

13

How long is NAC given for?

NAC is infused over 1 hour rather than the previous 15 minutes to reduce the number of adverse events

14

What is the Kings College criteria for liver transplantation?

King's College Hospital criteria for liver transplantation (paracetamol liver failure)

Arterial pH < 7.3, 24 hours after ingestion

or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy

15

What is the basis of graft rejection?

Graft rejection occurs because allografts have allelic differences at genes that code immunohistocompatability complex genes. The main antigens that give rise to rejection are:
1) ABO blood group
2) Human leucocyte antigens (HLA)
3) Minor histocompatability antigens

16

What is ABO matching?

ABO incompatibility will result in early organ rejection (hyperacute) because of pre existing antibodies to other groups. Group O donors can give organs to any type of ABO recipient whereas group AB donor can only donate to AB recipient.

17

What HLA alleles are important for transplantation and how many matches should ideally be made?

The four most important HLA alleles are:

HLA A
HLA B
HLA C
HLA DR

An ideal organ match would be one in which all 8 alleles are matched (remember 2 from each parent, four each = 8 alleles). Modern immunosuppressive regimes help to manage the potential rejection due to HLA mismatching. However, the greater the number of mismatches the worse the long term outcome will be. T lymphocytes will recognise antigens bound to HLA molecules and then will then become activated. Clonal expansion then occurs with a response directed against that antigen.

18

What are the three types of graft rejection?

Hyperacute. This occurs immediately through presence of pre formed antigens (such as ABO incompatibility).
Acute. Occurs during the first 6 months and is usually T cell mediated. Usually tissue infiltrates and vascular lesions.
Chronic. Occurs after the first 6 months. Vascular changes predominate.

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