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Published on: November 27, 2019
Avacopan-Associated Hepatotoxicity: Clinical Signal, Liver Injury Patterns, and Plausible Mechanisms
Luis Guillermo Herrera-Jiménez1, Sebastián Arguedas-Chacón2, Jeaustin Mora-Jiménez3
1Department of Pharmacy, University of Costa Rica, San José, CRI.
Cureus
|June 29, 2026
Summary
Avacopan, used for ANCA-associated vasculitis, may cause liver injury, particularly cholestatic-biliary issues. Careful monitoring is recommended due to potential risks, especially within the first six months of treatment.
Area of Science:
- Pharmacology
- Hepatology
- Immunology
Background:
- Avacopan is an oral C5a receptor antagonist for severe ANCA-associated vasculitis.
- A potential hepatobiliary safety concern has been associated with avacopan use.
Purpose of the Study:
- To review clinical, real-world, pharmacovigilance, and regulatory evidence on avacopan-associated liver injury.
- To emphasize reported injury patterns and plausible mechanisms.
Main Methods:
- Targeted literature search (PubMed/MEDLINE, Embase, Scopus, Web of Science).
- Inclusion of regulatory documents, prescribing information, and safety communications (FDA, EMA, LiverTox).
- Analysis of pre-approval trials, case reports, observational cohorts, and FDA Adverse Event Reporting System (FAERS) data.
Main Results:
- Hepatic adverse events were more frequent in avacopan trials.
- FAERS analyses revealed over 3,000 avacopan-related adverse events, including DILI and VBDS.
- Cholestatic-biliary injury is the most concerning phenotype, with onset often within 1-3 months, and can be fatal.
Conclusions:
- Avacopan use requires baseline liver assessment and close monitoring, especially in the first six months.
- The mechanism is likely multifactorial idiosyncratic DILI, influenced by host factors and drug interactions.
- Prompt interruption is advised if significant liver injury is suspected, given confounding therapies.
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