De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature

World J Gastroenterol. 2019 Sep 21;25(35):5356-5375. doi: 10.3748/wjg.v25.i35.5356.


Background: Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients.

Aim: To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients.

Methods: A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.

Results: Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences.

Conclusion: The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

Keywords: Adult liver transplant; Cancer; Clinical operational tolerance; De novo malignancies; Graft rejection; Immune system; Immunosuppression minimization; Immunosuppression weaning; Pediatric liver transplant.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Allografts / immunology
  • Child
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immune Tolerance / drug effects
  • Immunosuppression Therapy / standards
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Liver / immunology
  • Liver Transplantation / adverse effects*
  • Neoplasms / epidemiology*
  • Neoplasms / immunology
  • Neoplasms / prevention & control
  • Patient Selection*
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / immunology
  • Postoperative Complications / prevention & control
  • Withholding Treatment / standards


  • Immunosuppressive Agents