Assessing the Impact of Suboptimal Donor Characteristics on Mortality After Liver Transplantation: A Time-dependent Analysis Comparing HCC With Non-HCC Patients

Wallace, David; Walker, Kate; Charman, Susan C.; Suddle, Abid; Gimson, Alex; Rowe, Ian; Callaghan, Chris; Cowling, Thomas E; Heaton, Nigel; Meulen, Jan van der

doi:10.1097/tp.0000000000002559

Cited by 19 publications

(43 citation statements)

References 26 publications

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“…Adjustment for differences in recipient characteristics only or for both recipients and donor characteristics had minimal effects on the observed time trends in post‐transplantation outcomes of recipients with or without HCC. Instead, tumour recurrence was identified as the main factor responsible for the consistently poorer long‐term survival among recipients with HCC. Accordingly, improvements in the longer‐term survival of recipients with HCC are more likely to be influenced by changes in the selection of such patients for liver transplantation than by donor‐related factors.…”

Section: Discussionmentioning

confidence: 99%

“…Instead, tumour recurrence was identified as the main factor responsible for the consistently poorer long‐term survival among recipients with HCC. Accordingly, improvements in the longer‐term survival of recipients with HCC are more likely to be influenced by changes in the selection of such patients for liver transplantation than by donor‐related factors.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown previously that patients who receive a liver transplant as treatment for HCC are on average in better physical condition with fewer signs of end‐stage liver disease than patients who receive a liver transplantation for other reasons. This in turn may have a positive effect on short‐term post‐transplant outcomes. However, survival of recipients with HCC in the longer term is affected negatively by recurrence of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…This in turn may have a positive effect on short‐term post‐transplant outcomes. However, survival of recipients with HCC in the longer term is affected negatively by recurrence of cancer. Therefore, a national population‐based cohort study that explored time trends in short‐term and longer‐term post‐transplant mortality was carried out, separately for recipients with and those without HCC.…”

Section: Introductionmentioning

confidence: 99%

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Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK

Wallace

Cowling

Walker

et al. 2020

British Journal of Surgery

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Background: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short-and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016.Methods: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics.Results: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35⋅2 per cent in era 4 for recipients with HCC, and from 0⋅2 to 24⋅1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28⋅3 per cent in era 1 to 16⋅9 per cent in era 4 (adjusted HR 0⋅47, 95 per cent c.i. 0⋅35 to 0⋅63) for recipients with HCC, and from 20⋅4 to 9⋅3 per cent (adjusted HR 0⋅44, 0⋅36 to 0⋅53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0⋅20, 0⋅10 to 0⋅39; 90 days to 5 years: adjusted HR 0⋅52, 0⋅35 to 0⋅75; P = 0⋅043) and for non-HCC recipients (0-90 days: adjusted HR 0⋅32, 0⋅24 to 0⋅42; 90 days to 5 years: adjusted HR 0⋅52, 0⋅40 to 0⋅67; P = 0⋅024). Conclusion:In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK

Wallace

Cowling

Walker

et al. 2020

British Journal of Surgery

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“…( 27 ) The present study found no difference in HCC recurrence rates between the DCD and DBD groups, consistent with recent literature on the topic. ( 11,28 ) The fact that survival was worse in HCC patients at higher risk for recurrence who received a DCD liver but recurrence rates were similar between groups is meaningful and points toward the DCD graft itself as a contributor to the difference in survival. These findings support a “two‐hit” hypothesis where patients who, first, are at high risk for recurrence and, then, receive a DCD liver have particularly poor post‐LT patient and graft survival.…”

Section: Discussionmentioning

confidence: 99%

Donation After Circulatory Death Is Associated With Similar Posttransplant Survival in All but the Highest‐Risk Hepatocellular Carcinoma Patients

et al. 2020

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Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) receive a higher proportion of livers from donation after circulatory death (DCD) donors compared with non‐HCC etiologies. Nevertheless, data on outcomes in patients with HCC receiving DCD grafts are limited. We evaluated the influence of DCD livers on post‐LT outcome among HCC patients. We identified 7563 patients in the United Network for Organ Sharing (UNOS) database who underwent LT with Model for End‐Stage Liver Disease score exceptions from 2012 to 2016, including 567 (7.5%) who received a DCD donor organ and 6996 (92.5%) who received a donation after brain death (DBD) donor organ. Kaplan‐Meier probabilities of post‐LT HCC recurrence at 3 years were 7.6% for DCD and 6.4% for DBD recipients (P = 0.67) and post‐LT survival at 3 years was 81.1% versus 85.5%, respectively (P = 0.008). On multivariate analysis, DCD donor (hazard ratio, 1.38; P = 0.005) was an independent predictor of post‐LT mortality. However, a survival difference after LT was only observed in subgroups at higher risk for HCC recurrence including Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score ≥4 (DCD 57.0% versus DBD 72.6%; P = 0.02), alpha‐fetoprotein (AFP) ≥100 (60.1% versus 76.9%; P = 0.049), and multiple viable tumors on last imaging before LT (69.9% versus 83.1%; P = 0.002). In this analysis of HCC patients receiving DCD versus DBD livers in the UNOS database, we found that patients with a low‐to‐moderate risk of HCC recurrence (80%‐90% of the DCD cohort) had equivalent survival regardless of donor type. It appears that DCD donation can best be used to increase the donor pool for HCC patients with decompensated cirrhosis or partial response/stable disease after locoregional therapy with AFP at LT <100 ng/mL.

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Assessing the Time‐Dependent Impact of Performance Status on Outcomes After Liver Transplantation

et al. 2020

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BaCKgRoUND aND aIMS: Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period ("epoch") after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non-HCC recipients. appRoaCH aND ReSUltS: We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow-up (0-90 days and 90 days to 1 year) and in different eras of transplantation (1995-2005 and 2006-2016). 2107 HCC and 10,693 non-HCC patients were included. One-year survival decreased with worsening PS in non-HCC recipients where 1-year survival was 91.9% (95% confidence interval [CI], 88.3-94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7-80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4-93.2) and 83.1% (95% CI, 61.0-93.3), respectively. Reduction in survival in non-HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post-LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40-0.74) and non-HCC recipients (0.48; 95% CI, 0.42-0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively). CoNClUSIoNS: Impact on mortality of the recipient's pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non-HCC recipients and across the full range of PS.

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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

Abstract: Conception of the project, data analysis, interpretation of results and write up of the manuscript. Mrs Susan Charman: interpretation of results and write up of the manuscript.

Cited by 19 publications

References 26 publications

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK

Donation After Circulatory Death Is Associated With Similar Posttransplant Survival in All but the Highest‐Risk Hepatocellular Carcinoma Patients

Assessing the Time‐Dependent Impact of Performance Status on Outcomes After Liver Transplantation

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