Hepatocellular cancer and recurrence after liver transplantation: what about the impact of immunosuppression?

Abstract

Liver transplantation (LT) has originally been designed to treat hepatobiliary malignancies. The initial results of LT for hepatocellular cancer (HCC) were, however, dismal this mainly due to the poor patient selection procedure. Better surgical and perioperative care and, especially, the refinement of selection criteria led to a major improvement of results, making HCC nowadays (again!) one of the leading indications for LT. This evolution is clearly shown by the innumerable reports aiming to further extend inclusion criteria for LT in HCC patients. Nonetheless, the vast majority of papers only deals with morphologic (tumour diameter and number) and (only recently) biologic (tumour markers and response to locoregional treatment) parameters to do so. Curiously enough, the role of both the immune competent state of the recipient as well as the impact of both immunosuppression (IS) type and load has been very poorly addressed in this context, even if it has been shown for a long time, based on both basic and clinical research, that they all play a key role in the outcome of any oncologic treatment and in the development of de novo as well as recurrent tumours. This chapter aims to give, after a short introductive note about the currently used inclusion criteria of HCC patients for LT and about the role of IS in carcinogenesis, a comprehensive overview of the actual literature related to the impact of different immunosuppressive drugs and schemes on outcome of LT in HCC recipients. Unfortunately, up to now solid conclusions cannot be drawn due to the lack of high-level evidence studies caused by the heterogeneity of the studied patient cohorts and the lack of prospectively designed and randomized studies. Based on long-term personal experience with immunosuppressive handling in LT some proposals for further clinical research and practice are put forward. The strategy of curtailing and minimising IS should be explored in the growing field of transplant oncology taking thereby into account the immunological privilege of the liver allograft. These strategies will become more and more compelling when further extending the indications in which adjuvant chemotherapy will probably become an inherent part of the therapeutic scheme of HCC liver recipients.

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

“…But in the transplant setting, postoperatively high immunosuppressive doses are administered in order to achieve liver graft acceptance, which depresses the natural anti-cancer properties of the immunological defence. Apart from development of de-novo cancers, this may lead to acceleration of metastatic spread, implantation and growth of circulating tumor tissue in HCC patients [136,137] .…”

Hepatocellular cancer and liver transplantation: necessity to go from chaos to order

“…Внедрение протоколов минимизации иммуносупрессии, несомненно, будет важной вехой на пути расширения критериев отбора на трансплантацию [37,38].…”

Liver transplantation for metastatic wild-type gastrointestinal stromal tumor in the era of molecular targeted therapies: Report of a first case

“…2,3 Several decades ago, Pichlmayr advocated for the potential role of LT in the treatment of both advanced and rare oncologic conditions. 4,5 We present an unusual indication of LT for liver-only metastases from WT-GIST.…”

“…kinase-mTOR-mediated signal. This cell-signaling pathway stimulates key components of carcinogenesis, such as cell growth, proliferation, and survival 5. The MAPK pathway is activated via several different routes, including upstream growth factor receptor tyrosine kinases and downstream mutations in gene components and is reportedly inhibited by mTORis 14.…”