Transplants

Background

• Provides a treatment option of end-stage organ disease

Specific organ transplants

Liver

• Liver transplant is high in demand, despite the use of both cadaveric and living liver donations- 10% of those listed for a transplant will die waiting for one; 600 procedures are performed every year in the UK and around 6000 people will be living with a transplanted liver; most are performed in younger patients (<60)
• Indications include
  • Acute liver failure (10%)
  • Metabolic diseases (6%)
  • Cirrhosis (71%)
    • First episode of SBP; Diuretic resistant ascites; recurrent variceal haemorrhage; development of hepatocellular carcinoma; persistent hepatic encephalopathy; poor liver function (bilirubin >100μmol/l (5.8mg/dl) in PBC)
    • MELD score >12 or UKELD score >49; Child Pugh score >7
  • Hepatocellular carcinoma (11%)
• To be listed in the UK- patients should have a >50% projected post-transplant chance of 5-year survival and
  • estimated 1-year mortality without transplantation of more 9% (UKELD>49) OR
  • HCC diagnosed radiologically as either a single lesion <5cm or < 3 multiple lesions < 3cm each without macrovascular invasion or metastases OR
  • a feature(s) suggestive of poor prognosis e.g. diuretic-resistant ascites; hepatopulmonary syndrome; chronic encephalopathy; intractable pruritus; familial amyloidosis; primary hyperlipidaemia; polycystic liver disease; recurrent cholangitis
• Patients must show a commitment to alcohol abstinence prior to liver transplant
• Super-urgent listing is reserved for patients with Acute liver failure (previously well) who meet the King’s College Criteria

Renal

• HLA matching is important (DR > B > A)

Complications

Rejection

• Some form of immune response is inevitable against transplant tissues.  Because of huge variability between individual HLA proteins, unless patients are immunosuppressed, the transplant will invariably fail
  • Class I HLA include A, B and C; Class II include DP, DQ and DR
    • DR is most important for matching, followed by B and then A
• Rejection reactions can be classified as
  • Hyperacute (preformed antibodies- minutes to hours)
    • Usually against blood group antigens (minimised by group matching although not prevented as patients have preformed antibodies)
    • Reaction may be seen during surgery as anastamoses are made
    • There is no preventative treatments- only management is removal of the organ
  • Accelerated acute cellular (reactivation of pre-sensitised T cells and secondary antibody response- days)
  • Acute (cytotoxic T cell mediated with primary activation of T cells- days-weeks)
    • Most common; caused usually by HLA mismatch
    • Causes graft deterioration; fever, pain and tenderness
    • Usually can be managed by increasing immunosuppression
    • NB there is also an acute vascular rejection (mediated by antibodies/complement) which can cause a vasculitis type picture (generalised or local to graft)
  • Chronic (antibody mediated vascular damage- months-years; controversial as to whether this is a true immune rejection reaction)
    • Fibrosis and scarring
    • Effectively transplant failure (re-transplant may be required)

Complications of Immunosuppression

• Major complications are infections and malignancy

• Prophylactic antibiotics may be useful.
• Do not use live vaccines

Graft vs Host Disease

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