4.3 Review

Liver Toxicity with Cancer Checkpoint Inhibitor Therapy

Journal

SEMINARS IN LIVER DISEASE
Volume 38, Issue 4, Pages 366-378

Publisher

THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0038-1667358

Keywords

hepatotoxicity; immune-related adverse events; checkpoint inhibitor; CTLA-4; programmed cell death protein 1

Funding

  1. AASLD Pinnacle award
  2. Merck Sharp Dohme Corp
  3. Bristol Myers Squibb
  4. Incyte

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Immune checkpoint inhibition targeted against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Hepatotoxicity from checkpoint inhibitors is a less common irAE and often mild, while its incidence and severity vary based on the class and dose of checkpoint inhibitor, monotherapy versus combination therapy, and the type of cancer. Histological assessment of suspected irAEs is nonspecific and can show a variety of features. Hepatic irAEs can require discontinuation of checkpoint inhibitor therapy and treatment with immunosuppressive agents.

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