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The Liver - Part 6: liver transplantation.

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VOL: 102, ISSUE: 03, PAGE NO: 30

Helen L. Day, MSc, BSc, RGN, RSCN, DipN, is paediatric critical care clinical educator and outreach facilitator

Rachel M. Taylor, MSc, RGN, RSCN, DipRes, is nurse researcher; both at Paediatric Liver Centre, King's College Hospital, London

Liver transplantation is the accepted treatment for a wide variety of liver diseases. In the final part of this series on the liver, we review the indications and contraindications for transplantation, examine the different types of transplantation and outline the short and long-term complications.

Liver transplantation is the accepted treatment for a wide variety of liver diseases. In the final part of this series on the liver, we review the indications and contraindications for transplantation, examine the different types of transplantation and outline the short and long-term complications.

Chronic and acute liver disorders as presented in parts 4 and 5 of this series are often the main reasons for liver transplantation. Patients are assessed and deemed eligible for transplantation according to transplant listing criteria. Patients with chronic liver disease (CLD) will be considered for transplantation if their life expectancy is estimated at <18 months="" and="" there="" is="" clinical="" opinion="" that="" the="" patient="" will="" survive="" for="" more="" than="" five="" years="" after="" transplantation.="">

In addition a number of quality-of-life and other clinical indicators will be considered. Patients with acute liver failure (ALF) are considered for the supra-urgent list if the INR (international normalised ratio) is less than four in a child under two years of age. In those aged two onwards there are nine other listing categories dependent on aetiology and various clinical indicators of liver function (UK Transplantation, 2005).

There are no absolute, internationally agreed, contraindications for transplantation and each patient is assessed as an individual. However, certain pre-transplant factors decrease the chance of successful outcome. These include: sepsis, severe cardiovascular disease, multi-organ failure, uncontrolled congenital immune deficiency, extra-hepatic malignancy, mitochondrial disease, advanced encephalopathy (grade four) with severe neurological impairment, diffuse thrombosis of the portal system or significant psychosocial issues (Samuel et al, 2000).

Types of transplantation
Unlike other solid organ transplants liver transplantation is based on blood group not HLA (human leukocyte antigens) tissue typing, because the liver is less susceptible to HLA mediated rejection. The shortage of organs has led to innovative surgical techniques enabling an increase in the organ availability. It is possible to reduce larger organs to fit a child or to split the organ so there are two functioning allografts, each with a bile duct, venous system and sufficient cellular mass to sustain hepatic function (Busuttil and Goss, 1999). Therefore, from a single liver there are now a number of transplant possibilities: whole organ, left lobe, right lobe, left lateral segment or monosegment.

Auxiliary transplantation (Fig 1) can also be performed whereby part of a healthy donor liver is grafted with recipient liver. This is beneficial for patients with metabolic disorders, where the liver has normal function but has an enzymatic defect. Addition of the donor segment enables correction of the defect (Rela et al, 1997). Auxiliary liver transplantation is also used in ALF because the healthy graft maintains liver function while the damaged native liver regenerates, allowing cessation of immunosuppression (Jaeck et al, 2002).

Immunosuppressive agents are required throughout life and are essential to prevent post-transplant rejection of the organ. Immunosuppression is often the cause of many long-term complications.

Early complications
While every effort is made to prevent complications, there may be certain factors predisposing the patient to development of life-threatening complications in the early postoperative period. The main surgical complications are summarised in Table 1. Other complications include:

- Infection is the most common cause of morbidity and mortality after transplantation, with a prevalence of 40-73 per cent. Between one to six months post transplant, infections are usually caused by viruses or opportunistic pathogens. After six months post transplant, community-acquired infections are more common, such as respiratory viruses and pneumococcal pneumonia (Sherlock and Dooley, 1997);

- Acute rejection is the most common early complication after transplantion, developing in approximately 30-70 per cent of patients (McCaughan, 2000). The presenting features of acute rejection are fever, lethargy, jaundice, dark urine, pale stools, pruritus, ascites or anorexia. Diagnosis of acute rejection is confirmed by liver biopsy. Initial treatment is a short course of methylprednisolone, which successfully resolves rejection in 75-80 per cent of cases (Mor et al, 1992);

- Chronic (ductopenic) rejection occurs in approximately 1-10 per cent of patients, usually six weeks to six months after, but it can occur at any time. The patient is usually asymptomatic but can present as unresolved acute cellular rejection, progressive jaundice or pruritus. Late chronic rejection usually follows an episode of late acute rejection and is often associated with non-adherence. There is no specific treatment for chronic rejection. Some grafts can be rescued with increased immunosuppressive therapy. However, the majority will fail and the patient will require retransplantation (Brown and Williams, 2001; Ryckman et al, 2001).

Long-term physical complications
As patients are surviving longer following transplantation, secondary illnesses are becoming more common. Such illnesses include cardiovascular disease, renal dysfunction, bone disease, growth failure in children, and de novo malignancy (Sherlock and Dooley, 1997).

Cardiovascular disease

Hypertension occurs in a significant number of patients (approximately 30-80 per cent). Hyperlipidaemia and hypertension occur as a result of decreased renal function and hepatic production of triglycerides, and contribute to the development of atherosclerotic cardiovascular disease that may predispose patients to greater risk for premature heart disease (Brown and Williams, 2001).

Renal dysfunction

Immunosuppressive agents such as tacrolimus and ciclosporin (calcineurin-inhibitors) are known to reduce renal plasma flow, resulting in a decrease in glomerular filtration rate by approximately 50 per cent. Nephrotoxicity occurs in 20-70 per cent of non-renal transplant recipients and strategies have been in place to try and reduce the use of calcineurin inhibitors, such as the addition of MMF (Mycophenolate mofetil) (Aw et al, 2001; Brown and Williams, 2001). Renal function should be investigated at each clinic visit.

Bone disease

Osteodystrophy and osteopenia are a known complication of CLD because cholestasis is accompanied by fat malabsorption and fat-soluble vitamin deficiency. Accordingly, all patients with CLD are administered vitamin supplements (Sherlock and Dooley, 1997; Argao et al, 1993). In the post-transplant period bone disease may be prevented by the early withdrawal of corticosteroids, especially in the over 60s. Loss of bone mineral density may contribute to an increased risk of bone fractures following liver transplant, therefore vitamin supplements may be given to post-transplant patients and intravenous bisphosphonates can reduce the incidence of postoperative fractures (Brown and Williams, 2001).

Growth failure

In children chronic liver disease impairs growth by affecting nutritional status, and the growth hormone (GH) - insulin-like growth factor (IGF) axis. Post-transplant growth can be enhanced by aggressive nutritional support and is influenced by height prior to transplantation and graft function after transplantation. Growth may also be impaired by the use of high doses of immunosuppression, particularly steroids (Holt et al, 1997).

De novo malignancy

Approximately six per cent of patients will develop malignancy, usually within five years of transplantation. Many are related to immunosuppression including lymphoproliferative diseases and skin cancer, so patients are advised to use liberal amounts of sun block. Other rarer malignancies have been reported, including Kaposi's sarcoma, fibrosarcoma and smooth muscle tumours (Sherlock and Dooley, 1997).

Advanced surgical techniques and the development of effective immunosuppressive therapies have enabled liver transplantation to be performed in any age group with a high graft and patient survival rate.

This article has been double-blind peer-reviewed.

For related articles on this subject and links to relevant websites see

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