Management of immune checkpoint inhibitors-induced liver toxicity in cancer

Pharmacological immune checkpoint inhibitors (ICI) restore the anti-tumor properties of T-lymphocytes, but unfortunately can engender auto-immune-like disorders. Those, frequent and of variable severity, sometimes target the liver parenchyma. Liver toxicity of ICI firstly leads to alteration of liver function tests (ALFT) with a risk of clinical decompensation. The appearance of ALFT should lead the clinician to exclude a non-immunological injury or a tumoral invasion of the liver parenchyma. In case of high grade ALFT, liver biopsy is necessary for diagnosis purpose. In ICI-induced hepatoxicity, histology examination shows most frequently a lobular acute hepatitis associated with lymphocytic infiltrates, but with different features than those encountered in primary auto-immune hepatitis. The management of ICI-related ALFT depends of their severity. Discontinuation of ICI is recommended for ALFT ≥ grade 2, and corticosteroid therapy for ALFT ≥ grade 3, or grade 2 without any improvement after ICI discontinuation. Addition of mycophenolate may be indicated whether corticosteroid inefficiency. Reintroduction of ICI is inadvisable for the most severe toxicities. The management of ALFT occurring on underlying chronic hepatopathy has not got consensual guidelines so far, but they should take account of the basal grade of ALFT and their worsening level under ICI therapy. The situation becomes more complex with associations between ICI and anti-angiogenic agents or cytotoxic chemotherapies where each of the drugs can be hepatotoxic. Thus, liver biopsy is primordial to figure out the mechanism of liver toxicity.