Liver transplantation

Liver transplants are usually from a cadaver donor but can more rarely be partial live donor transplant. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomical position as the original liver.

Live donor transplants usually involve transplanting half a liver, thus being associated with a significant mortality risk to the donor of 0.8%.¹

With an increasing number of patients on the waiting list and the ongoing shortage of livers available, domino liver transplantation (DLT) became an option to further expand the organ donor pool. DLT utilises the explanted liver of one liver transplant recipient as a donor graft in another patient.²

Indications for liver transplantation

Over 90% of liver transplants in the UK are performed for chronic liver disease, where a gradual destruction of liver tissue results in jaundice, ascites, encephalopathy with coagulopathy and hypoalbuminaemia. A smaller number will have acute liver failure, and an even smaller number are transplanted for a non-failing liver, where there is survival advantage (eg, hepatopulmonary syndrome, persistent and intractable pruritus, polycystic liver disease, familial hyperlipidaemia, recurrent cholangitis and familial amyloidosis).

See reference link for a more complete list of indications.³

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 five 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 there is a worse outcome for those aged 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 - eg, the Model for End-stage Liver Disease (MELD) and UK End-stage Liver Disease (UKELD). Recent data suggest that the MELD score and low serum sodium concentration provide good evidence of outcome following liver transplantation.⁴

• Other factors are also taken into account - eg, 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. See also the article on Liver Failure.

• Transplant offers are based on multidisciplinary team meetings, and patients who are refused are offered a second opinion.

Complications of liver transplantation⁵

• 1st week: primary graft non-function, biliary complications, acute kidney injury, infections (surgical, chest).

• 1-4 weeks: acute liver allograft rejection, hepatic artery thrombosis.

• 1-3 months: CMV, fungal infection, acute liver allograft rejection, biliary complications, hepatic artery thrombosis, hepatitis C recurrence.

• 3-6 months: acute liver allograft rejection, biliary complications, EBV hepatitis.

• Over 6 months: chronic rejection, EBV hepatitis, portal vein thrombosis, disease recurrence, late hepatic artery thrombosis, post-transplant lymphoproliferative disease.

Aftercare¹

• Immunosuppression - a combination of drugs is used, consisting of a calcineurin inhibitor, steroids (weaned after six weeks unless there is 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.

• Transplant rejection - 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.

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

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.

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.

Routine checks to include

• FBC, U&E, LFT - frequency is dependent on the time since the transplant and the clinical course.

• Monitoring drug levels - this will usually be performed by the transplant centre.

• Metabolic risk and cardiovascular risk surveillance - eg, 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 two 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 (the preferred statin, as it has the least drug interactions), angiotensin-converting enzyme (ACE) inhibitors 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, cervical, breast and skin cancer (partly depends on age and gender).

• Osteoporosis - bone mineral density should be measured and treated if necessary.⁶

• Vaccinations (eg, 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.

Prognosis⁵

Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. 12-month graft survival rates in the UK exceed 80%.

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.