Immune‐related hepatitis related to checkpoint inhibitors: Clinical and prognostic factors

• Published in: Liver international Vol. 40; no. 8; pp. 1906 - 1916
• Main Authors: Riveiro‐Barciela, Mar, Barreira‐Díaz, Ana, Vidal‐González, Judit, Muñoz‐Couselo, Eva, Martínez‐Valle, Fernando, Viladomiu, Lluís, Mínguez, Beatriz, Ortiz‐Velez, Carolina, Castells, Lluís, Esteban, Rafael, Buti, María
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2020
• Subjects: acute liver failure; Autoimmune diseases; autoimmune hepatitis; checkpoint inhibitors; Corticoids; Corticosteroids; drug‐induced liver injury; Hepatitis; IgG antibody; Immune checkpoint; immune‐related adverse events; immune‐related hepatitis; Immunoglobulin G; Immunosuppression; immunotherapy; Inhibitors; Liver; Liver diseases; Medical prognosis; Oncology; PD-1 protein; PD-L1 protein; Immune-related hepatitis; Acute liver failure; Autoimmune hepatitis; Check-point inhibitors; Immune-related adverse events; Immunotherapy; Drug-induced liver injury
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.14489

Background & Aims Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune‐related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). Methods This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. Results Twenty‐eight cases of severe irH were recorded: 10 on anti‐CTLA‐4 ± anti‐PD1/PD‐L1 and 18 on anti‐PD1/PD‐L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune‐related adverse events after a median cycles of 11 (range 6‐36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty‐five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001). Conclusions Immune‐related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.