Calcineurin-Inhibitor Discontinuation Could Reduce the Risk of De Novo Malignancies After Liver Transplantation for Alcohol-Related Liver Disease

Clin Transplant. 2024 Oct;38(11):e70014. doi: 10.1111/ctr.70014.

Abstract

Background: De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol-related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation.

Methods: From 1990 to 2015, all patients transplanted for ALD were included.

Results: A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years.

Conclusion: Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non-modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD.

Keywords: alcohol‐related liver disease; calcineurin inhibitors; de novo malignancies; liver transplantation; survival.

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors* / administration & dosage
  • Calcineurin Inhibitors* / therapeutic use
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Liver Diseases, Alcoholic* / etiology
  • Liver Diseases, Alcoholic* / surgery
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Neoplasms* / etiology
  • Postoperative Complications / epidemiology
  • Postoperative Complications / prevention & control
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents