Editorials
Digestive system diseases Surgery Child health
Volume 213 - Issue 10

Retransplantation should be offered to children with liver graft failure

Author:  James Neuberger

Med J Aust 2020; 213 (10): 456-457. || doi: 10.5694/mja2.50833
Published online: 16 November 2020

The increasing use of split livers for in children has effectively increased the donor organ supply

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The increasing use of split livers for in children has effectively increased the donor organ supply

While the coronavirus disease 2019 (COVID‐19) pandemic has focused public and medical attention on how limited life‐saving medical resources must sometimes be rationed,1 the transplantation medicine community has been struggling with this question for decades. Despite increases in the numbers of organ donors, both deceased and living, the continuing shortage of organs not only means that many patients who might benefit from transplantation are not being referred or listed, but as many as one in seven people listed for a transplant die or become too sick before an organ becomes available.2,3 Consequently, access to life‐saving organs is, in effect, rationed, undertaken according to agreed guidelines that vary between jurisdictions and depend, in part, on the balance between the availability of organs and the clinical need. The criteria for selecting recipients and for allocating organs include need (priority for the sickest patients), equity, justice, utility, benefit, and the avoidance of futility.4

Matching donor and recipient size is important, but children have the advantage that they can receive livers not only from similarly sized donors but also from adults, as some livers can be divided to provide two grafts (split grafts): the left lobe (segments II and III) for a child recipient and the extended right lobe graft (segments I and IV–VIII) for an adult recipient.5 Over the past two decades, the use of split livers has increased, and, as surgical experience has increased and the selection criteria have been refined, outcomes have improved markedly.6 Increasing use of split and reduced size livers for transplantation means that the number of deaths among children waiting for transplants has been reduced, and is considerably lower than for adults.2,3 Splitting a liver requires considerable surgical expertise, logistic support, and careful selection of donor, organ, and recipient. Although outcomes for adult recipients of split livers are slightly inferior to those for adults receiving whole organs,7 the approach is considered ethically sound.8

Long term survival is now excellent for children receiving liver allografts; indeed, a recent study in the United States estimated that 30‐year survival for people under 18 years who received transplants between 2007 and 2018 will be 80%.9 However, major challenges remain. Patient survival is lower than for a normal matched population,10 and liver transplantation is associated with increased risks of cardiovascular disease, some malignancies and infections, renal failure, and recurrent disease.11 Quality of life after transplantation is also reduced: one recent study reported that more than one‐half of adolescent liver transplant recipients exhibited poor school and cognitive functioning, probably reflecting attention and executive function deficits.12 It is not clear whether the deficits are the legacy of the pre‐transplantation illness or have other causes. While improved follow‐up should reduce the causes of premature death described above, other problems include the fact that patient and graft survival is lower for children from lower socio‐economic status areas.13 Non‐compliance with post‐transplantation therapy is also more common in children than adults, and may lead to graft loss.14

Early graft failure is usually the consequence of either primary non‐function or vascular problems, such as hepatic artery thrombosis.15 Late graft failure (after one year) may be caused by immunological rejection (sometimes associated with non‐compliance), recurrent or de novo disease, vascular problems, or biliary disease.15

For patients with graft failure, the only therapeutic option is re‐grafting. In the study reported in this issue of the MJA,16 Jeffrey and colleagues analysed data from the Australia and New Zealand Liver and Intestinal Transplant Registry (ANZLITR), and provide strong evidence for their conclusion that children should not be denied access to further grafts. The authors found that patient and graft survival had improved significantly for children receiving second or further transplants during 1986–2017; further, during 2001–2017, the graft type, the number of retransplantations, and the reason for graft failure did not influence survival. As the overall number of regrafts was relatively small, the impact of some risk factors may not have been apparent. For example, a recent evaluation of the US Scientific Registry of Transplant Recipients (SRTR) identified that factors that influenced outcomes for children after regrafting included recipient age, primary diagnosis, survival time of the first graft, graft type, and donor age; survival was similar for low risk retransplant and primary transplant recipients.17 It must also be remembered that outcomes of retransplantation reflect the careful selection and matching of recipients with donors; conclusions cannot simply be extrapolated to all children with graft failure, and clinicians must continue to carefully select and match recipients and donors.

In contrast to adults, for whom organ availability is a major limiting factor, the use of split livers for transplantation in children increases the donor supply, and therefore allows innovation and the expansion of indications for transplantation. While it is important to focus on outcome after transplantation, this measure should not be the sole criterion of program success, but should be applied in conjunction with other outcomes, such as benefit and utility; that is, the increased survival associated with transplantation.

The study by Jeffrey and colleagues16 provides strong evidence that justifies liver retransplantation in children, based on an analysis of a well designed and supported comprehensive registry in which clinicians work closely with managers, statisticians, and patients, among others.18 The study also indicates that transplantation policies must be sufficiently flexible to allow appropriate evolution and extension of the boundaries imposed by national selection guidelines and to support clinicians in developing new treatments and exploring new indications for transplantation, even in the context of a rationed service, such as liver transplantation.

Author

  • James Neuberger1
  • 1. University Hospitals Birmingham NHS Foundation Trust, Birmingham, The United Kingdom

Correspondence: james.neuberger@uhb.nhs.uk

Competing interests

No relevant disclosures.

References

Linked content

  • MJA Research: Outcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis

Provenance: Commissioned; externally peer reviewed.

View this article on Wiley Online Library