It is estimated that there are currently 6,000 liver transplant survivors in the UK.¹ This number is likely to increase, as survival is increasing and about 600 people receive a new liver each year. 14% will die waiting, or be deemed too sick before a transplant becomes available.¹ Transplants are usually from a cadaver donor but can more rarely be partial live donor transplant. Live donor transplants are fairly recent to the UK and usually involve transplanting half a liver, thus being associated with a significant mortality risk to the donor of 0.8%.^1,2

Indications

The following table lists a few of the indications for liver transplantation (see reference for full table).¹

Patients on the waiting list¹

• As for other organs, the demand for livers outweighs the supply.
• Initial assessment for a transplant is based on trying to answer the following three questions:
  • Is there no alternative treatment for the liver disease? Aim for 50% survival at 5 years.
  • If transplant is not curable, is recurrence rate acceptable?
  • What are the unrelated medical conditions that will contribute to overall outcomes?
• Transplants are offered at any age (although worse outcome for those over 65 years).
• It is important for specialists to determine the risk of death in patients with advanced liver disease.
• There are scoring systems available to help with this, e.g. the Model for End-stage Liver Disease (MELD) and UK End-stage Liver Disease (UKELD). Recent data suggests that the MELD score and low serum sodium concentration provide good evidence of outcome following liver transplantation.³
• Other factors are also taken into account, e.g. those associated with poor prognosis, such as resistant ascites.
• For "super-urgent" cases arising from acute liver failure, decisions for transplantation have to be made in a matter of days. Commonly the King's College criteria are used to make the decision.
• Transplant offers are based on multidisciplinary team meetings and patients who are refused are offered a second opinion.

Complications of liver transplantation

Many centres will give short-term antibiotic and antiviral prophylaxis. Other drugs may also be given prophylactically, e.g. septrin for pneumocystis and fluconazole for fungal sepsis.¹

Aftercare

• Immunosuppression - a combination of drugs is used, consisting of a calcineurin inhibitor, steroids (weaned after 6 weeks unless concomitant hepatitis C) and azathioprine. Subsequent immunosuppression may be tacrolimus or ciclosporin alone, or dual therapy with either azathioprine or mycophenolate. Tacrolimus may be superior to ciclosporin but patients are at risk of developing diabetes mellitus.¹
• Transplant rejection - acute rejection usually presents with raised liver enzymes, bilirubin and eosinophilia, and may be asymptomatic. Patients who are symptomatic usually experience non-specific symptoms, e.g. lethargy, fever and abdominal pain. On the other hand, chronic rejection usually occurs after 1 year and is referred to as the "vanishing bile duct syndrome". Again patients may have abnormal liver function (hepatitic or cholestatic picture), non-specific symptoms or jaundice with pruritus.¹

Approach to a liver transplant recipient who turns up to surgery unwell¹

Acute illness

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

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, e.g. 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.

Routine checks to include

• FBC, U&E, LFT - frequency dependent on time since transplant and clinical course.
• Monitoring drug levels - this will usually be performed by the transplant centre.
• Metabolic risk and cardiovascular risk surveillance, e.g. fasting lipids and glucose (diabetes develops in 35%), blood pressure (develops in 60% - due to medications in part) and weight gain (20% who are non-obese on receiving a liver transplant become so 2 years later).
• Cardiovascular risk reduction - 20% of late deaths after liver transplantation are related to cardiovascular causes. Risk reduction should involve lifestyle measures and drugs, such as pravastatin (preferred statin, as least drug interactions), angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers as any other patient.
• Monitor ethanol intake - harmful drinking is less prevalent than initially thought and estimated at 6.5%.
• Smoking cessation if applicable.
• Cancer surveillance- looking for colonic, cervix, breast and skin cancer (partly depends on age and gender).
• Osteoporosis - bone mineral density should be measured and treated if necessary.⁴
• Vaccinations, e.g. influenza and pneumococcus, but avoid live vaccines.
• Mental health - patients and their carers may have difficulty adjusting to the post-transplant life and depression should be actively sought.

Most transplant centres will have a specialist nurse or nurses who are usually a good point of first contact in the department.

Prognosis

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.¹ Disease recurrence can occur and will reduce the prognosis, e.g. 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.¹

Document references

1. Hirschfield GM, Gibbs P, Griffiths WJ; Adult liver transplantation: what non-specialists need to know. BMJ. 2009 May 22;338:b1670. doi: 10.1136/bmj.b1670.
2. Christie B; First NHS funded live liver transplant programme to go ahead. BMJ. 2005 Nov 12;331(7525):1102.
3. Kim WR, Biggins SW, Kremers WK, et al; Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008 Sep 4;359(10):1018-26. [abstract]
4. Levitsky J, Cohen SM; The liver transplant recipient: what you need to know for long-term care. J Fam Pract. 2006 Feb;55(2):136-44. [abstract]
5. Kallwitz ER, Cotler SJ; Care of the liver transplant patient. Dis Mon. 2008 Jul;54(7):486-507.

Internet and further reading

• Living-donor liver transplantation, NICE Interventional Procedure Guideline (2006)
• Transplantation guidelines (various), British Transplantation Society (various dates)
• National Liver Transplant Standards, Dept of Health, 2005

Acknowledgements