Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two‐centre analysis using competing risk analysis

Cusumano, Caterina; Carlis, Luciano De; Centonze, Leonardo; Lesourd, Romain; Sandri, Giovanni Battista Levi; Lauterio, Andrea; Carlis, Riccardo De; Ferla, Fabio; Sandro, Stefano Di; Camus, Christophe; Jézéquel, Caroline; Bardou-Jacquet, Édouard; Rayar, Michel

doi:10.1111/tri.13950

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…Our study found that donor age is associated with recurrence. This diverges from the study of Cusumano and colleagues but supports Orci and colleagues’ finding that donor age older than 60 years is a risk factor for recurrence 30 , 31 . Similarly, the impact of donor warm ischaemia time as seen with the use of DCD liver grafts on HCC recurrence is controversially discussed in the literature.…”

Section: Discussionsupporting

confidence: 44%

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience

Wehrle,

Raj,

Maspero

et al. 2024

International Journal of Surgery

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Background: Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume center. Methods: A prospectively maintained database was used to identify HCC patients undergoing LT from 2000-2020 with>3 years follow-up. Data was obtained from the center database and electronic medical records. The Metroticket 2.0 HCC-specific five-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. Results: 569 patients met criteria. Median follow-up was 96.2 months (8.12 y; IQR 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% (n=504) and 86.6% (n=493). Five-year RFS and OS were 78.9% (n=449) and 79.1% (n=450). Median Metroticket 2.0 score was 0.9 (IQR 0.9-0.95). Tumor size>3 cm (P=0.012), increasing tumor number on imaging (P=0.001) and explant pathology (P<0.001) was associated with recurrence. Transplant within Milan (P<0.001) or UCSF-criteria (P<0.001) had lower recurrence rates. Increasing AFP-values were associated with more HCC-recurrence (P<0.001) and reduced OS (P=0.008). Chemoembolization was predictive of recurrence in the overall population (P=0.043) and in those outside Milan criteria (P=0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival>87.5% for predicting recurrence. This cut-off was able to predict RFS (P<0.001) in the total cohort and predict both, RFS (P=0.007) and OS (P=0.016) outside-Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts (n=15/58, 25.6%, P=0.009). Donor age was associated with a higher HCC-recurrence (P=0.006). Both total ischemia time (TIT)>6hours (P=0.016) and increasing TIT correlated with higher HCC-recurrence (P=0.027). The use of DCD-grafts for outside-Milan candidates was associated with increased recurrence (P=0.039) and reduced survival (P=0.033). Conclusion: This large two-center analysis confirms favorable outcomes after LT for HCC. Tumor size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e., donor age, DCD-grafts, ischemia time) was associated with poorer outcomes.

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Section: Discussionsupporting

confidence: 44%

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience

Wehrle,

Raj,

Maspero

et al. 2024

International Journal of Surgery

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“…This suggests that people on the waitlist because of HCC could potentially receive organs from older donors without negatively affecting their prognosis. 15 Given these insights, we aimed to identify the best group of recipients who could benefit most from younger donors, factoring in the tumor characteristics. Allocating young, high-quality organs properly is extremely vital, considering the current shortage of donors.…”

Section: Discussionmentioning

confidence: 99%

“… 14 A more recent study considering these pathological factors contradicted previous beliefs, highlighting the lack of a consensus in the current disclosure. 14 , 15 Moreover, the last decade has witnessed several policy changes for treating HCC, with a rising preference for using marginal donors. 16 , 17 Therefore, it becomes essential to reevaluate how donor characteristics influence transplant outcomes for patients with HCC.…”

mentioning

confidence: 99%

The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients

Akabane,

Esquivel,

Kim

et al. 2024

Transplantation Direct

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Background. The role of donor age in liver transplantation (LT) outcomes for hepatocellular carcinoma (HCC) is controversial. Given the significant risk of HCC recurrence post-LT, optimizing donor/recipient matching is crucial. This study reassesses the impact of young donors on LT outcomes in patients with HCC. Methods. A retrospective review of 11 704 LT cases from the United Network for Organ Sharing database (2012–2021) was conducted. The study focused on the effect of donor age on recurrence-free survival, using hazard associated with LT for HCC (HALT-HCC) and Metroticket 2.0 scores to evaluate post-LT survival in patients with HCC. Results. Of 4706 cases with young donors, 11.0% had HCC recurrence or death within 2 y, and 18.3% within 5 y. These outcomes were comparable with those of non-young donors. A significant correlation between donor age and post-LT recurrence or mortality (P = 0.04) was observed, which became statistically insignificant after tumor-related adjustments (P = 0.32). The Kaplan-Meier curve showed that recipients with lower HALT-HCC scores (<9) and Metroticket 2.0 scores (<2.2) significantly benefited from young donors, unlike those exceeding these score thresholds. Cox regression analysis showed that donor age significantly influenced outcomes in recipients below certain score thresholds but was less impactful for higher scores. Conclusions. Young donors are particularly beneficial for LT recipients with less aggressive HCC, as indicated by their HALT-HCC and Metroticket 2.0 scores. These findings suggest strategically allocating young donors to recipients with less aggressive tumor profiles, which could foster more efficient use of the scarce donor supply and potentially enhance post-LT outcomes.

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“…Orci et al demonstrated that patients who received a liver from elderly donors (>60 y) or with diabetes or a body mass index (BMI) of ≥35 kg/m 2 had a higher post-transplant recurrence [ 61 ]. Advanced donor age was also found to promote HCC recurrence in other studies, but the results appear controversial [ 62 , 63 , 64 ].…”

Section: Risk Factors For Liver Cancer Recurrence After Transplantationmentioning

confidence: 97%

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

Parente

Carvalho

Eden

et al. 2022

IJMS

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Tumor recurrence after liver transplantation has been linked to multiple factors, including the recipient’s tumor burden, donor factors, and ischemia-reperfusion injury (IRI). The increasing number of livers accepted from extended criteria donors has forced the transplant community to push the development of dynamic perfusion strategies. The reason behind this progress is the urgent need to reduce the clinical consequences of IRI. Two concepts appear most beneficial and include either the avoidance of ischemia, e.g., the replacement of cold storage by machine perfusion, or secondly, an endischemic organ improvement through perfusion in the recipient center prior to implantation. While several concepts, including normothermic perfusion, were found to reduce recipient transaminase levels and early allograft dysfunction, hypothermic oxygenated perfusion also reduced IRI-associated post-transplant complications and costs. With the impact on mitochondrial injury and subsequent less IRI-inflammation, this endischemic perfusion was also found to reduce the recurrence of hepatocellular carcinoma after liver transplantation. Firstly, this article highlights the contributing factors to tumor recurrence, including the surgical and medical tissue trauma and underlying mechanisms of IRI-associated inflammation. Secondly, it focuses on the role of mitochondria and associated interventions to reduce cancer recurrence. Finally, the role of machine perfusion technology as a delivery tool and as an individual treatment is discussed together with the currently available clinical studies.

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Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two‐centre analysis using competing risk analysis

Cited by 10 publications

References 25 publications

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience

The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

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