History of drug allergies poses risk for ‘fatal outcome’ in drug-induced liver injury
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In patients with idiosyncratic drug-induced liver injury, previous history of an allergic reaction related to drugs correlated with worse clinical outcomes, including death, according to data presented at the EASL Congress.
“There are no studies conducted in a population of patients with well-characterized DILI as it is a low incidence population,” Ismael Alvarez-Alvarez, MD, from the Biomedical Research Institute of Malaga in Spain, said during the presentation. “Our aim was to compare the clinical presentation of DILI in patients with and without prior drug allergies and to assess the associations between the drugs responsible for DILI and prior drug allergy.”
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Using the Spanish DILI registry, Alvarez-Alvarez and colleagues assessed demographics and clinical history of patients with idiosyncratic DILI and determined history of prior drug allergies. They identified 912 patients with a first episode of DILI, of whom 61 (6.7%) had confirmed prior drug allergies and 851 (93.3%) did not.
According to researchers, patients with prior drug allergies tended to be older than those without (60 years vs. 54 years; P = .009) and also were more likely to have underlying chronic disease (P = .016).
Hepatocellular injury was the most observed liver injury in both groups; however, patients with prior drug allergies had lower median alkaline phosphatase values at DILI diagnosis, (1.4 vs. 1.6 × ULN; P = .045) and higher aspartate aminotransferase (9.4 vs. 6.2 × ULN; P = 0.047) and alanine aminotransferase (12 vs. 9.5) values. Notably, patients with prior drug allergies had significantly lower platelet counts (189 vs. 226 x 103/mL; P = 0.011).
Fatal outcomes were reported in nine patients with prior drug allergy who progressed to acute liver failure, of whom seven died and two underwent liver transplantation. They were more likely to be women, have higher total bilirubin (14 vs. 4.2; P < .001) and AST (26 vs. 7.8; P = .026), and lower platelet counts (127 vs. 190; P = .013).
Alvarez-Alvarez noted drugs most responsible for DILI in patients without a prior drug allergy included amoxicillin-clavulanate (23%), anti-tuberculosis drugs (4.4%), herbal and dietary supplements (3.6%), ibuprofen (2.9%), flutamide (2.5%) and atorvastatin (2.4%). Among those with prior drug allergies, amoxicillin (20%), ebrotidine (6.6%), anti-TB drugs and levofloxacin (4.9%), and ciprofloxacin, diclofenac and isoniazid (3.3%) were most responsible for DILI.
Additionally, penicillin (32%), acetylsalicylic acid and codeine (6.3% each) were the most frequent drugs responsible for prior drug allergies in patients with DILI.
Using the Bootstrap-enhanced least absolute shrinkage operator for analysis, researchers reported that prior drug allergy, hepatocellular injury, female sex, total bilirubin, AST and platelet count were factors that correlated with fatal outcome.
“This is the first study that analyzed the role of prior drug allergies in a large cohort of well-characterized DILI cases,” Alvarez-Alvarez said. “We saw a drug allergy may be an independent factor of fatal outcome in DILI; therefore, patients with suspected DILI should have a thorough pharmacologic history and be screened for prior drug allergies. DILI patients with prior drug allergy require close monitoring for early detection of worsening of their clinical course.”
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Munoz P, et al. Abstract OS-007: Prior drug allergies are associated with worse outcome in patients with idiosyncratic drug-induced liver injury: an analysis from the Spanish DILI registry. Presented at: International Liver Congress; June 21-24, 2023; Vienna (hybrid meeting).
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