P1808 - Presence of NAFLD in Patients Receiving Immune Checkpoint Inhibitors Significantly Increases the Prevalence of Immune Mediated Hepatotoxicity

Osama Hamid, MD, MRCPI¹, Ahmed Eltelbany, MD, MPH¹, Abdul Mohammed, MD², Imad Asaad, MD^1
1Cleveland Clinic Foundation, Cleveland, OH; ²MetroHealth Medical Center, Cleveland, OH

Introduction: Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies the interrupt co-inhibitory signaling pathways (e.g cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1 & its ligand PD-L1) and promote immune mediated elimination of cell tumors. The use of ICPI has emerged in recent years in the field of both solid & liquid tumor therapy. Immune medicated hepatotoxicity is well known adverse event associated with ICPI utilization. The aim of this study is to assess the prevalence of hepatotoxicity in patients with underlying non-alcoholic fatty liver disease (NAFLD) receiving ICPI

Methods: We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT) we identified adults received ICPI (regardless of indication) from 2011 to 2021. We identified adults with diagnosed with NAFLD. We excluded patients diagnosed with alcoholism, viral hepatitis, other drug induced liver injury, & biliary disease. Of this cohort, we collected data on hepatocellular injury and cholestasis. Risk factors known to be associated with NAFLD like diabetes mellitus type 1 or 2 (DM), hyperlipidemia (HLD) & Obesity (defined BMI >30) were also collected. Univariable and multivariable logistic regression were performed, adjusting to demographics and risk factors, to investigate hepatotoxicity (in patients with and without NAFLD) receiving ICPI. We used R version 3.6.3 for statistical analysis.

Results: Out of 63.7 million active adults in the database, 18150 (0.02%) received ICPI, of them 1090 (6.0%) has documented NAFLD. Patients with Age > 65 years received ICPI were majority (61.3%). Male were 58.2% of this cohort. Percentage of patients on ICPI (without NAFLD) who had DM, HLD and Obesity were 30.7, 61.5 and 23.3, respectively. These factors were higher in the cohort with underlying NAFLD (DM 79.8%, HLD 87%, Obesity 88%). Presence of NAFLD in Patients on ICPI is associated with higher prevalence of hepatocellular injury (OR 3.62 [2.60-3.64]) vs (OR 2.34 [2.48-2.41]). Compared to patients on ICPI without NAFLD, presence of NAFLD was associated with slightly higher odds of developing cholestasis (OR 2.54 [2.48-2.61]) vs (OR 2.13 [2.01-2.15]).

Discussion: Patients with NAFLD have significant higher risk of hepatotoxicity from Immune checkpoint inhibitors. Further studies need to be done to better predict drug induced liver injury in this patient population.



Disclosures:


Osama Hamid, MD, MRCPI¹, Ahmed Eltelbany, MD, MPH¹, Abdul Mohammed, MD², Imad Asaad, MD¹. P1808 - Presence of NAFLD in Patients Receiving Immune Checkpoint Inhibitors Significantly Increases the Prevalence of Immune Mediated Hepatotoxicity, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.