Clinical and histologic features of azithromycin-induced liver injury.
Level 4 - case-series / case-control
Prospective registry-based case series without a control group
PubMed 25111234 · doi:10.1016/j.cgh.2014.07.054
What was done
Patients with azithromycin-induced liver injury and causality adjudicated as definite, highly likely, or probable were identified from the Drug-Induced Liver Injury Network (DILIN) Prospective Study. Demographic characteristics, clinical features, laboratory measurements, histological findings, and 6-month clinical outcomes were analyzed.
What was found
Eighteen patients were identified (72% female; mean age, 37 years), with causality scored as definite (n = 1), highly likely (n = 9), or probable (n = 8). The median duration of azithromycin treatment was 4 days (range, 2-7 days). In 16 patients, abnormal liver tests were first detected a median of 14 days after stopping azithromycin (range, 9-20 days). Common presenting symptoms were jaundice, abdominal pain, nausea, and pruritus. The pattern of liver injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. Mean peak levels were alanine aminotransferase 2127 IU/L, alkaline phosphatase 481 IU/L, and total bilirubin 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients, and 2 individuals had severe cutaneous hypersensitivity reactions. At 6 months, 8 patients had recovered, 4 had chronic injury, 1 died, 1 underwent liver transplantation, and outcomes were unavailable for 4 patients. Both patients who died or underwent transplantation had underlying chronic liver disease.
Why it matters
This study defines the clinical presentation and latency of azithromycin hepatotoxicity, showing that liver injury is predominantly hepatocellular and often manifests 1 to 2 weeks after stopping therapy, with potential for severe or fatal outcomes.
Limits
The study is limited by a small sample size (n = 18), lack of a control group, missing 6-month outcome data for 4 patients, and potential confounding by pre-existing chronic liver disease in the patients who died or required transplantation.
Cited by
- supports Azithromycin is associated with liver and kidney damage and has negative interactions with approximately 62 other medications.