The optimal time for liver transplantation after cancer immunotherapy has been established

Hepatocellular carcinoma (HCC) accounts for 80 to 90% of primary liver cancers. According to the World Health Organization, there will be 905,700 new cases and 830,200 deaths worldwide in 2020. In Switzerland, the Statistical Office records 960 new cases and 720 deaths annually. HCC is the third cause of cancer deaths worldwide and the fifth in Switzerland.

Among the existing treatments for HCC, liver transplantation is the most effective treatment option, offering individual patients the possibility of long-term remission or even complete cure.

Immunotherapy with immune checkpoint inhibitors (ICIs), which stimulate the immune system of patients to attack cancer cells, has recently become widespread, with very promising results: positive response in one third of cases and even complete tumor disappearance in some patients.

Given this efficacy, ICI is gradually becoming the first line of treatment for advanced HCC.

Currently, the response to ICI is not sustainable, as stopping treatment can trigger a recurrence of the cancer.

“To address this problem, we want to combine immunotherapy and transplantation, that is, to offer patients who respond to ICI treatment a new liver transplant capable of eliminating both cancer and underlying liver disease,” explains Beat Moeckli, Senior Resident in Abdominal Surgery at the Investigator in the Department of Surgery at UNIGE Faculty of Medicine and first author of the study.

Unfortunately, the use of ICI puts patients at increased risk of rapid transplant rejection.

“Immunotherapy stimulates the immune system in such a way that it recognizes tumors as foreign entities. In the case of transplantation, immune cells stimulated in this way will also potentially attack the graft with greater efficiency. We should therefore stop ICT treatment before transplantation to reduce this risk,” he continues.

Therefore, in order to reconcile the two approaches, it is necessary to determine the optimal treatment window, namely the interval between stopping ICI treatment and liver transplantation. To determine this, an international team led by HUG and UNIGE conducted a retrospective study involving 29 leading clinics in Europe, Asia and the US.

In total, the Geneva team analyzed data from 119 HCC patients receiving immunotherapy before liver transplantation to assess the incidence of transplant rejection, transplant loss, and recurrences after transplantation.

The results showed that the shorter the interval between the last ICI procedure and graft transplantation, the higher the risk of rejection. An interval of less than 30 days increases the risk of rejection 21.3-fold. An interval of 30 to 50 days increases the risk only 9.5-fold. In contrast, with an interval of more than 50 days, the risk of rejection was significantly reduced.

Thanks to this seminal work, the selection criteria for liver transplantation for HCC patients have been optimized. In fact, this study contributed to the definition of models that combine biomarkers and total tumor volume to optimize patient selection and reduce the risk of recurrence.

This study represents a significant step toward the development of formal recommendations for liver transplantation for patients receiving immunotherapy.

“These guidelines will be of great importance and are expected to be developed soon. We hope that our study will play a key role in increasing access to transplantation and therefore improving remission rates,” concludes Moeckli.

More information is available in the journal Hepatology

Severance Gangnam Hospital Republic of Korea,SeoulLeave a request

Shalimov National Institute of Surgery and Transplantology Ukraine,KyivLeave a request

Published: 10.03.2025

Updated: 09.03.2025

Medical author, Medical editor:

Stepan Yuk

Medical expert:

PhD. Olexandr Voznyak