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Chemotherapy hepatotoxicity and dose modification in patients with liver disease

Justin Floyd, DO
Thomas Archibald Kerr, MD, PhD
Section Editors
Reed E Drews, MD
Keith D Lindor, MD
Deputy Editor
Diane MF Savarese, MD


Patients undergoing cytotoxic chemotherapy require careful assessment of liver function both prior to and during therapy. Potential interactions between the liver and chemotherapy fall into two categories:

Direct chemotherapy-induced hepatotoxicity.

Potentiation of preexisting liver disease, especially viral hepatitis. Altered hepatic drug metabolism due to underlying liver disease can result in higher or more persistent drug levels, thereby causing increased systemic toxicity (particularly myelosuppression) or worsening of liver function because of chemotherapy-induced hepatotoxicity.

The interrelationship between the liver and chemotherapy is reviewed here. General aspects of drug metabolism and patterns of hepatic injury are discussed separately, as is reactivation of hepatitis B (HBV) viral infection in patients treated with immunosuppressive therapy, and hepatotoxicity associated with checkpoint inhibitor immunotherapy (ipilimumab, pembrolizumab, nivolumab), as used for advanced melanoma and non-small cell lung cancer. (See "Drugs and the liver: Metabolism and mechanisms of injury" and "Drug-induced liver injury" and "Hepatitis B virus reactivation associated with immunosuppressive therapy" and "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Hepatotoxicity'.)


Mechanisms — Most hepatotoxic drug reactions are idiosyncratic and classified mechanistically either as immunologic (hypersensitivity) or metabolic [1]. These reactions typically are neither dose dependent nor predictable. (See "Drugs and the liver: Metabolism and mechanisms of injury", section on 'Mechanisms of drug-induced hepatotoxicity'.)

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