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Assessing the Impact of Suboptimal Donor Characteristics on Mortality After Liver Transplantation

A Time-dependent Analysis Comparing HCC With Non-HCC Patients

Wallace, David, MSc1,2; Walker, Kate, PhD1; Charman, Susan, MSc1; Suddle, Abid, MD2; Gimson, Alex, MD3; Rowe, Ian, PhD4,5; Callaghan, Chris, PhD6; Cowling, Tom, PhD1; Heaton, Nigel, FRCS2; van der Meulen, Jan, PhD1

doi: 10.1097/TP.0000000000002559
Original Clinical Science—Liver
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Background. Patients who receive a liver transplant for hepatocellular carcinoma (HCC) often receive poorer-quality livers. Tumor recurrence also has a negative effect on posttransplant outcomes. We compared mortality of HCC and non-HCC recipients in different posttransplant time periods (epochs) to separate the impact of these different risk factors on short-term and longer-term posttransplant survival.

Methods. We identified a population-based cohort of first-time liver transplant recipients (aged ≥16 years) between 2008 and 2016 in the United Kingdom. We used Cox regression to estimate hazard ratios (HRs) comparing posttransplant mortality between HCC and non-HCC patients in 3 posttransplant epochs: 0 to 90 days, 90 days to 2 years, and 2 to 5 years, with adjustment first for recipient and later also for donor characteristics.

Results. One thousand two hundred seventy HCC and 3657 non-HCC transplant recipients were included. Five-year posttransplant survival was 74.5% (95% confidence interval [CI] 71.2%–77.5%) in HCC patients and 84.6% (83.0%–86.1%) in non-HCC patients. With adjustment for recipient characteristics only, mortality of HCC patients was lower but not statistically significantly different in the first 90 days (HR, 0.76; 95% CI, 0.53–1.09; P = 0.11), but significantly higher thereafter (90 days to 2 years: HR, 1.99; 95% CI, 1.48–2.66; P < 0.001; 2 to 5 years HR, 1.77; 95% CI, 1.30–2.42; P < 0.001). Further adjustment for donor characteristics had little impact on these results.

Conclusions. HCC recipients have poorer 5-year posttransplant survival than non-HCC recipients, most likely because of tumor recurrence. The more frequent use of poorer-quality donor organs for HCC does not explain this difference.

1 Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.

2 Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, United Kingdom.

3 The Liver Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

4 Liver Unit, St James’ Hospital and University of Leeds, Leeds, United Kingdom.

5 Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom.

6 Department of Transplantation, Renal Unit, Guy’s Hospital, London, United Kingdom.

Received 30 August 2018.

Accepted 3 November 2018.

D.W. is funded by a Doctoral Research Fellowship from the National Institute of Health Research. J.v.d.M. is partly supported by the NHS National Institute for Health Research Collaboration for leadership in Applied Health Research and Care North Thames at Bart’s Health NHS Trust. The funder of the study, National Institute for Health Research, had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. D.W., K.W., and J.v.d.M. had full access to all the data in the study, take responsibility for the integrity of the data and the accuracy of the data analysis, and had final responsibility for the decision to submit for publication.

J.v.d.M. reports grants from Healthcare Quality Improvement Partnership during the conduct of the study. The other authors declare no conflicts of interest.

This report is independent research arising from a Doctoral Research Fellowship (DRF-2016-09-132) awarded to David Wallace and supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, Health Education England or the Department of Health.

D.W. involved in the conception of project, literature review, data analysis, interpretation of results, and write up of the manuscript. K.W. involved in the conception of the project, data analysis, interpretation of results, and write up of the manuscript. S.C. involved in the interpretation of results and write up of the manuscript. A.S. involved in the interpretation of results and write up of the manuscript. A.G. involved in the interpretation of results and write up of the manuscript. I.R. involved in the interpretation of results and write up of the manuscript. C.C. involved in the interpretation of results and write up of the manuscript. N.H. involved in the interpretation of results and write up of the manuscript. J.v.d.M. involved in the conception of project, literature review, data analysis, interpretation of results, and write up of the manuscript. All authors have given final approval for this manuscript to be submitted to Transplantation.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: David Wallace, MSc, Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom, WC1H 9SH. (david.wallace@lshtm.ac.uk).

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