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Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents
Author(s) -
Suzman Daniel L.,
Pelosof Lorraine,
Rosenberg Amy,
Avigan Mark I.
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13746
Subject(s) - medicine , autoimmune hepatitis , adverse effect , common terminology criteria for adverse events , discontinuation , liver injury , immunotherapy , immune system , hepatitis , ipilimumab , immunology , oncology
Immune checkpoint inhibitors ( ICI s) block CTLA ‐4, PD ‐1 and PD ‐L1, or other molecules that control antitumour activities of lymphocytes. These products are associated with a broad array of immune‐related toxicities affecting a variety of organs, including the liver. ICI ‐associated immune‐mediated hepatitis ( IMH ) ranges in severity between mild and life‐threatening and is marked by findings that bear both similarities as well as differences with idiopathic autoimmune hepatitis. Hepatotoxic events are often detected in clinical trials of ICI s that are powered for efficacy. Risk levels for ICI ‐induced liver injury may be impacted by the specific checkpoint molecule targeted for treatment, the ICI dose levels, and the presence of a pre‐existing autoimmune diathesis, chronic infection or tumour cells which infiltrate the liver parenchyma. When patients develop liver injury during ICI treatment, a prompt assessment of the cause of injury, in conjunction with the application of measures to optimally manage the adverse event, should be made. Strategies to manage the risk of IMH include the performance of pretreatment liver tests with regular monitoring during and after ICI treatment and patient education. Using Common Terminology Criteria for Adverse Events developed at the National Cancer Institute to measure the severity level of liver injury, recommended actions may include continued ICI treatment with close patient monitoring, ICI treatment suspension or discontinuation and/or administration of corticosteroids or, when necessary, a non‐steroidal immunosuppressive agent. The elucidation of reliable predictors of tumour‐specific ICI treatment responses, as well as an increased susceptibility for clinically serious immune‐related adverse events, would help optimize treatment decisions for individual patients.