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

Abstract

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. DISCUSSION: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.

Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment

“…152 A recent large case series from the DILIN group has shown this typical pattern to be more common in patients >60 years of age, whereas patients younger than 20 are more likely to present with hepatocellular injury and hypersensitivity features. 153 Latency of injury is around 3 weeks and prognosis is guarded with 4% rate of death or liver transplantation. 153 Chronic DILI is common and occurs in 20% of patients.…”

“…153 Latency of injury is around 3 weeks and prognosis is guarded with 4% rate of death or liver transplantation. 153 Chronic DILI is common and occurs in 20% of patients. 39 Biopsies typically show cholestatic hepatitis, 153 while rare ductopenia 154 immunodeficiency syndrome 155 and African American individuals.…”

“…153 Chronic DILI is common and occurs in 20% of patients. 39 Biopsies typically show cholestatic hepatitis, 153 while rare ductopenia 154 immunodeficiency syndrome 155 and African American individuals. 156 More recently, a GWAS has identified HLA-B Ã 14:01 and HLA-B Ã 35:01 as risk alleles for TMP-SMX DILI in European and African American individuals, respectively.…”

“…153 Chronic DILI is common and occurs in 20% of patients. 39 Biopsies typically show cholestatic hepatitis, 153 while rare ductopenia 154 has been reported as well. Hepatotoxicity from TMP-SMX occurs frequently in patients with acquired immunodeficiency syndrome 155 and African American individuals.…”