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Background <p>Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with liver transplantation (LT) offering curative potential for patients in the early stages. While immune checkpoint inhibitors (ICIs) are effective in managing tumor progression, concerns about graft rejection persist. This study investigates how peri-LT ICIs administration affects rejection rates and survival outcomes in HCC patients.</p> Methods <p>This global study analyzed 386 HCC patients receiving Peri-LT ICIs therapy, integrating data from a systematic literature review and institutional registries. The risk of graft rejection and survival outcomes were assessed using logistic and Cox regression, along with restricted cubic splines modeling dose-response dynamics.</p> Results <p>Overall graft rejection rates did not significantly differ between Pre-LT (17.5%) and Post-LT (22.1%) ICI users (<i>P</i> = 0.351); however, Post-LT use was associated with higher rates of graft loss/dysfunction (47.1% vs. 25.9%, <i>P</i> &lt; 0.05) and rejection-related mortality (47.1% vs. 18.5%, <i>P</i> &lt; 0.05). In Pre-LT patients, washout periods &gt;30 days (OR = 0.36, 95% CI: 0.18–0.72, <i>P</i> = 0.004) and &gt;1.5 half-life counts (OR = 0.24, 95% CI: 0.12–0.50, <i>P</i> &lt; 0.001) were associated with reduced rejection risk. Post-LT, high PD-L1 expression on graft tissue correlated with increased rejection risk (<i>P</i> &lt; 0.001). Graft rejection following Pre-LT ICIs was linked to poorer overall survival (HR = 5.17, 95% CI: 2.21–12.24, <i>P</i> &lt; 0.001).</p> Conclusions <p>With careful management, peri-LT ICIs may be considered for HCC patients. Optimizing washout periods and monitoring graft PD-L1 expression may improve transplant outcomes.</p> Graphical Abstract <p></p>

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Immune checkpoint inhibitors use in liver transplantation for hepatocellular carcinoma: a global cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月2日

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  • Delin Ma,
  • Pengcheng Wei,
  • Qian Cheng,
  • Jialing Hao,
  • Zuyin Li,
  • Zhuomiaoyu Chen,
  • Wenzai Shi,
  • Zhigao Yuan,
  • Chen Lo,
  • Yongjing Luo,
  • Liyi Qiao,
  • Jie Gao,
  • Jiye Zhu,
  • Zhao Li

摘要

Background

Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with liver transplantation (LT) offering curative potential for patients in the early stages. While immune checkpoint inhibitors (ICIs) are effective in managing tumor progression, concerns about graft rejection persist. This study investigates how peri-LT ICIs administration affects rejection rates and survival outcomes in HCC patients.

Methods

This global study analyzed 386 HCC patients receiving Peri-LT ICIs therapy, integrating data from a systematic literature review and institutional registries. The risk of graft rejection and survival outcomes were assessed using logistic and Cox regression, along with restricted cubic splines modeling dose-response dynamics.

Results

Overall graft rejection rates did not significantly differ between Pre-LT (17.5%) and Post-LT (22.1%) ICI users (P = 0.351); however, Post-LT use was associated with higher rates of graft loss/dysfunction (47.1% vs. 25.9%, P < 0.05) and rejection-related mortality (47.1% vs. 18.5%, P < 0.05). In Pre-LT patients, washout periods >30 days (OR = 0.36, 95% CI: 0.18–0.72, P = 0.004) and >1.5 half-life counts (OR = 0.24, 95% CI: 0.12–0.50, P < 0.001) were associated with reduced rejection risk. Post-LT, high PD-L1 expression on graft tissue correlated with increased rejection risk (P < 0.001). Graft rejection following Pre-LT ICIs was linked to poorer overall survival (HR = 5.17, 95% CI: 2.21–12.24, P < 0.001).

Conclusions

With careful management, peri-LT ICIs may be considered for HCC patients. Optimizing washout periods and monitoring graft PD-L1 expression may improve transplant outcomes.

Graphical Abstract