The Impact of Patient Age and Corticosteroids in Patients With Sulfonamide Hepatotoxicity

• Published in: The American journal of gastroenterology Vol. 118; no. 9; pp. 1566 - 1575
• Main Authors: Fontana, Robert J., Kleiner, David E., Chalasani, Naga, Bonkovsky, Herbert, Gu, Jiezhun, Barnhart, Huiman, Li, Yi-Ju, Hoofnagle, Jay H.
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.09.2023; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adrenal Cortex Hormones - therapeutic use; Age; Antibiotics; Bilirubin; Causality; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - etiology; Cholestasis - pathology; Female; Hepatitis; Humans; Laboratories; Liver transplants; Male; Patients; Risk factors; Steroids; Sulfanilamide - adverse effects; Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects; United States > US
• DOI: 10.14309/ajg.0000000000002232
• ISSN: 0002-9270; 1572-0241

Sulfonamides 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. Between 2004 and 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. Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). 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 with 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 toward more rapid normalization of their laboratory abnormalities compared with 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. 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.