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

asasasas

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

Graft vs Host Disease

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