65 Characteristics of Liver Injury in Drug-induced Systemic Hypersensitivity Reactions

BACKGROUND: Liver is the second most commonly involved organ in drug-induced systemic hypersensitivity reactions (DiSH). Although liver function is very important indicator in the course of DiSH, there have been few studies about the characteristics of the liver injury. In present study, we investigated clinical characteristics of DiSH associated with liver injury (liver-DiSH) METHODS: We retrospectively reviewed medical records of 38 hospitalized patients who developed liver-DiSH (AST or ALT ≥80 IU/L) from January 2008 to February 2011 in a tertiary referral hospital. We analyzed culprit drugs, the type and degree of liver injury, and the effect of systemic corticosteroids. Fisher's exact test and Chi-square test and Mann-Whitney test were used for statistical analysis. RESULTS: Thirty-eight patients of liver-DiSH were enrolled, whose clinical phenotypes were Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (n = 9, 24%), drug reaction with eosinophilia and systemic symptoms (DRESS) (n = 23, 60%), maculopapular rash (MP rash) (n = 5, 13%) and acute generalized exanthematous pustulosis (AGEP) (n = 1, 3%). Antibiotics (n = 16/38, 41%) was the most common cause of liver-DiSH. Culprit agents of liver-DiSH were allopurinol (n = 3/9, 33%) in SJS/TEN and antibiotics (n = 13/23, 57%) in DRESS. Mortality tended to be higher in SJS/TEN than in DRESS (22% (2/9) vs 17% (4/23), P = 0.846). Degree of liver injury was statistically more severe in DRESS than in SJS/TEN (mean peak AST [423 IU/L vs 144 IU/L, P = 0.062], mean peak ALT [428 IU/L vs 156 IU/L, P = 0.013], mean peak ALP (alkaline phosphatase) [252 IU/L vs 85 IU/L, P = 0.002], mean total bilirubin [7.7 mg/dL vs 1.3 mg/dL, P = 0.064], and time required for AST/ALT to drop below 80 IU/L [15.8 days vs 4.1 days, P = 0.049]). Seventy-six percents (29/38) of patients were treated with systemic corticosteroid. The use of corticosteroid did not significantly affect both recovery of liver injury and mortality. CONCLUSIONS: Our results suggest that liver-DiSH has distinguished clinical characteristics according to the disease phenotypes. Further studies are needed to evaluate the role of systemic corticosteroid in liver injury in DiSH.