The impact of patient age and corticosteroids in patients with Sulfonamide hepatotoxicity.

UNLABELLED: OBJECTIVESSulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity.

METHODS: Between 2004 to 2020, 105 patients with hepatotoxicity attributed to trimethoprim/ sulfamethoxazole (TMP-SMZ) (n=93) or other sulfonamides (n=12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist.

RESULTS: Amongst the 93 TMP-SMZ cases, 52% were female, 7.5% less than 20 years old, and the median time to DILI onset was 22 days (range: 3 to 157). Younger patients were significantly more likely to have rash, fever, eosinophilia and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared to older patients (p< 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend towards more rapid normalization of their laboratory abnormalities compared to untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels.

CONCLUSIONS: Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury but further studies are needed.