S2341 Severe Immune Checkpoint Inhibitor-Induced Hepatitis: A 6-Month Follow-Up National Study

Introduction: Immune checkpoint inhibitors (ICI) are revolutionizing the treatment paradigm of many advanced malignancies. A known side effects of this drug class is immune-mediated end organ damage, including immune mediated hepatitis (IMH). Severe IMH (class 3 or 4) is treated in the inpatient setting. No national study has measured the long-term treatment outcomes of severe IMH. We aimed to bridge this gap using the largest national readmission database. Methods: We used the national readmission database (NRD) to identify adult patients admitted for ICI infusions in the United States from 2016 to 2022. The follow-up period was 6 months. Appropriate International Classification of Diseases, Tenth Revision (ICD-10)-CM codes were used to identify diagnoses and procedures. The primary outcome was patients’ demographics. The secondary outcomes were the incidence, readmission rate, mortality rate, of severe IMH as well as its associated rate of acute liver failure and resource utilization. Results: During the study period, 13,257 patients were hospitalized and received ICI. Of them, 9,014 (68%) were readmitted within 6 months. We identified 41 patients who developed IMH. The mean patient age was 48 years. The majority of patients were man, of higher income, and insured mainly by Medicare or private insurance. Most patients were treated at large teaching hospitals in large urban areas. Overall, rising annual incidence of IMH was observed over time, with a noticeable decline in 2020 likely due to the COVID-19 pandemic induced lower hospitalization rates for ICI infusions. The mean time to from infusion to development of IMH was 29 days. The 6-month mortality rate and acute liver failure rates were 4.6% and 5.1%, respectively. The mean length of stay was 16 days with an associated total hospitalization charges of $330,834. Conclusion: Unlike autoimmune hepatitis, severe IMH has a man and middle-age predominance. The incidence of severe IMH is low, indicating that IMH is a low-grade toxicity that resolves with cessation of ICI and corticosteroids for the most part. However, severe IMH occurs within 30 days of infusion and is associated with a substantial risk of mortality, acute liver failure and resource utilization. With dual ICI becoming more common, increased incidence of IMH is expected, and vigilant monitoring of the patients with the demographics we report is recommended for early identification and treatment to avoid detrimental patient outcomes.