Early Detection of de Novo Cancer in Liver Transplant Recipients

Background The risk of cancer in liver transplant recipients is twice the cancer risk in the general population and de novo cancers are one of the leading causes of death after liver transplantation. The immunosuppressive medication, used to prevent organ rejection, is considered a key factor increasing the risk of de novo cancer. Objectives I. Determine prevalence and incidence of de novo cancer in liver transplant recipients and build an algorithm to identify high-risk individuals II. Investigate if opportunistic viral infections (as a surrogate for over-immunosuppression) is associated with non-virus associated de novo cancers III. Investigate if cell free DNA fragmentation can be used to identify liver transplant recipients with de novo cancers and to identify cancer at an asymptomatic stage Methods The study is in collaboration with all five Scandinavian liver transplant centers in ScandiaTransplant (Copenhagen, Oslo, Gothenburg, Stockholm and Helsinki) and includes all liver transplant recipients from the centers. Data on demographics, de novo cancer and risk factors are retrieved from electronic health records, cancer registries and the ScandiaTransplant database (n=3628). Blood samples to perform viral and cell free DNA fragmentation analyses are retrieved from the biobank at Rigshospitalet (n=932). Implications The study includes a large cohort of liver transplant recipients from all of Scandinavia. With cancer as one of the primary causes of death in liver transplant recipients, new tools are needed to identify recipients with increased risk of developing de novo cancer. In particular, new tools allowing early diagnosis of de novo cancer enabling curative intended intervention. The study has potential to identify liver transplant recipients with increased risk of developing de novo cancer and reduce cancer related mortality.

Sex

All

Minimum age

20 Years

Maximum age

100 Years

Inclusion Criteria:

* All liver transplant recipients from the five centers between 20 and 100 years of age at time of transplantation, during the period 1.1.2010 - 31.12.2020 are included in the study (n=3628)
* For the nested case-control study: Plasma, serum and whole blood samples, collected pre-liver transplantation and sequentially during post-liver transplantation follow-up, from recipients in Scandinavia has been stored in a dedicated biobank at Rigshospitalet (n=932). Inclusion is ongoing and we expect to have included additionally 300 patients at the time of the proposed analyses.

Exclusion Criteria:

* Cancers arisen first 30 days post liver transplantation are excluded as it is considered a to be delayed diagnosis of pre-liver transplantation and not a de novo cancer.
* Donor-derived cancers or a relapse or metastatic disease from a cancer diagnosed prior to liver transplantation are excluded.