Chemical and Drug Induced Liver Injury

The condition is caused by hepatotoxic exposure to medications, their metabolites, herbal and dietary supplements, and chemicals from the environment. The supplied reviews specifically highlight immune checkpoint inhibitors as a cause of immune-mediated liver injury, and high-dose methotrexate as a drug associated with toxicity. No single cause applies to all cases because the entity is a broad exposure-related syndrome.

The biological mechanism varies by offending agent and injury pattern. For immune checkpoint inhibitor-associated liver injury, cytotoxic T lymphocytes play a central role and immunotherapy can activate innate and adaptive immune cells, producing hepatitis or cholangitis. For high-dose methotrexate toxicity, crystallization in the renal tubular lumen causes tubular toxicity and impaired clearance, which can prolong toxic exposure and worsen systemic adverse effects.

Risk depends on the specific exposure and host susceptibility. For methotrexate-associated toxicity, reported risk factors include prior renal dysfunction, volume depletion, acidic urine, and drug interactions. For immune checkpoint inhibitor liver injury, the abstracts indicate that risk factors are an active area of study, but they do not specify them in the supplied text.

Management is primarily removal or cessation of the offending agent and supportive treatment, with modality depending on severity and cause. For severe immune checkpoint inhibitor liver injury, the review states that cessation of the checkpoint inhibitor and initiation of immunosuppression are required, and steroids are described as the primary treatment for ICI hepatitis. The supplied grounding does not support a broader standard-of-care description beyond these treatment classes.