S1113 Risk of Idiosyncratic Drug-Induced Liver Injury Among Patients With Prior History of Drug Allergy

Abstract

INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is a rare but important cause of acute liver failure. The relationship between prior history of drug allergy and future risk of developing DILI is unknown, but some have suggested increased susceptibility. The primary aim of this study was to compare rates of DILI among patients with prior history of drug allergy versus patients without history of drug allergy. METHODS: The EMR was searched for all hospital admissions for possible DILI using ICD-10 T-codes for drug poisoning/toxicity and K-71 codes for toxic liver injury between 10/1/15 and 9/30/19. Clinically significant liver injury was defined as: 1) AST > 5 x ULN, 2) ALT > 5 x ULN, 3) ALP > 2 x ULN, 4) total bilirubin > 2.5 mg/dL, or 5) INR > 1.5. An expert opinion causality score (1/2/3 = probable-DILI, 4/5 = non-DILI), RUCAM score, and severity score were assigned to each case. Drug allergy was defined as significant adverse drug reaction such as hives, or anaphylaxis. Rates of probable-DILI among patients with prior history of drug allergy were compared to rates among those without prior drug allergy. RESULTS: Among 766,930 patients searched, 185 unique patients met inclusion criteria. After manual review of 147 cases, 37 cases of acetaminophen hepatotoxicity were excluded. In the remaining 110 cases, causality assessment identified probable-DILI in 67 patients (61%), whereas 43 (39%) had an alternative cause of liver injury, including ischemic hepatitis, and biliary obstruction. Sixty-one (55.5%) patients had history of drug allergy before DILI episode but none of the drugs was the same as those suspected for causing DILI. Compared to those without prior drug allergy, patients with prior drug allergy had a similar rate of DILI (67.3% vs. 55.7%, P = 0.24). Furthermore, the likelihood of death or liver transplantation among probable-DILI cases with prior drug allergy did not differ from those without prior drug allergy (5.9% vs. 6.1%, P = 1.0). Among probable DILI patients, the suspect drug was subsequently documented as a ‘drug allergy' in the EMR for only 24 (35.8%) patients. CONCLUSION: A prior history of drug allergy was not associated with a greater likelihood of subsequent DILI compared to other causes of acute liver injury. The low rate of suspect drug documentation as a “drug allergy” in the EMR after DILI episode may increase likelihood of inadvertent suspect drug re-challenge and adverse patient outcomes.