1 Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain. Electronic address: firstname.lastname@example.org.
2 State Key Laboratory of Translational Oncology, Department of Clinical Oncology; Sir YK Pao Centre for Cancer, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
3 Royal Free London NHS Foundation Trust and UCL Cancer Institute, London, UK.
4 Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
5 University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
6 I. Medical Department, University Medical Center, Mainz, Germany.
Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.