Immune checkpoint inhibitor-related hepatotoxicity: A review

Abstract

The application of immune checkpoint inhibitors (ICI) in advanced cancer has been a major development in the last decade. The indications for ICIs are constantly expanding into new territory across different cancers, disease stages and lines of therapy. With this increased use, adverse events including immune checkpoint inhibitor-related hepatotoxicity (ICH) have emerged as an important clinical problem. This along with the introduction of ICI as first- and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists. The incidence of ICH varies between 1%-20% depending on the number, type and dose of ICI received. Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI, corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity. The majority of patients with ICH recover and some may even safely recommence ICI therapy. Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.

Keywords: Adverse drug event; Drug-induced liver injury; Hepatitis; Immune checkpoint inhibitors; Immunosuppression; Immunotherapy.

Figure 1

Histopathological changes of inhibitor-related hepatotoxicity. A: Prominent perivenulitis (black arrow) with endothelialitis (orange arrow) in a case of ipilimumab related hepatotoxicity (hematoxylin and eosin, 400 ×); B: Lymphocytic cholangitis with prominent duct damage secondary to nivolumab (black arrows; hematoxylin and eosin, 400 ×).