What are the clinical features and outcomes of ivermectin‑associated hepatitis reported in case series?
Executive summary
Case series, pharmacovigilance data and isolated case reports describe ivermectin‑associated hepatic injury ranging from asymptomatic transaminase elevations to fulminant hepatitis; most published signals are sparse, heterogeneous and often confounded by co‑morbid illness or concurrent therapies (p1_s3; [2]; [4]/p1_s6). The strongest documented single‑patient example is a 2006 report of severe hepatitis after a single dose in a patient treated for filarial infection, while pharmacovigilance reviews identify a small cluster of hepatic adverse events among ivermectin exposures used for COVID‑19 and other indications (p1_s5/[5]; p1_s3).
1. Reports and case series that constitute the evidence base
Published evidence consists of individual case reports (the 2006 severe hepatitis case is the cited “first case”) and safety‑signal mining from large adverse‑event registries rather than prospective multicenter case series; a VigiBase pharmacovigilance review identified ivermectin use in 25 COVID‑19 cases, six of which included hepatic disorders (hepatitis, hepatocellular injury, cholestasis or abnormal liver tests) and post‑marketing sources note elevated ALT/AST and hepatitis among reported adverse events (p1_s5/[5]; [1]; p1_s4).
2. Typical clinical presentation described in the reports
When liver injury is reported, presentations range from laboratory‑only abnormalities (isolated ALT/AST elevations) to clinical hepatitis with jaundice and systemic symptoms; the VigiBase summary explicitly lists hepatitis, hepatocellular injury and cholestasis among reported events [1], and the case report described development of severe hepatitis identified about one month after a single ivermectin dose in a young patient (p1_s5/p1_s6). Postmarketing summaries also indicate that elevations in ALT and/or AST and occasional reports of hepatitis have occurred [2].
3. Timing, dose and treatment context — a heterogeneous picture
Timing and dosing vary across reports: the landmark single‑patient case followed a single standard therapeutic dose given for filariasis with hepatitis identified roughly one month later (p1_s5/p1_s6), while pharmacovigilance entries include ivermectin exposures used off‑label for COVID‑19 and in mass‑distribution programs for parasitic disease; VigiBase aggregates reports from many countries but does not standardize dose or timing in public summaries [1]. This heterogeneity complicates attempts to define a consistent latency or dose‑response relationship from existing series (p1_s3; [4]/p1_s6).
4. Outcomes reported: most recoveries, but severe cases and death are recorded
Available data show a spectrum of outcomes: many signals are limited to abnormal liver tests or transient injury, but there are documented severe cases — including the 2006 report of severe, clinically overt hepatitis and other registry entries where hepatic failure was noted as a complication or exclusion in neurological adverse‑event reviews (p1_s5/[5]; [3]; p1_s4). VigiBase identified serious hepatic disorders among a subset of ivermectin exposures used for COVID‑19, indicating that clinically significant injury has occurred in real‑world reporting systems [1].
5. Causality, confounders and limits of the case‑series evidence
Causality is uncertain in many reports: pharmacovigilance data are hypothesis‑generating but subject to reporting bias, incomplete clinical details and confounding by co‑medications, underlying infections (including severe COVID‑19 itself, which can cause liver enzyme abnormalities), and preexisting liver disease—factors acknowledged in the VigiBase analysis and in the exclusion criteria of neurological adverse event reviews [1] [3]. The literature therefore cannot robustly quantify risk or prove a consistent mechanistic link; the strongest individual causal claim rests on temporality and exclusion of other causes in the 2006 case report, not on systematic case‑series evidence (p1_s5/p1_s6).
6. Practical implications: vigilance, reporting and research priorities
Clinically, these signals warrant heightened vigilance for new jaundice or rising transaminases after ivermectin exposure, careful assessment of alternative causes, and reporting of suspected cases to pharmacovigilance systems so pooled analyses can improve risk estimates [1] [2]. Regulators and clinicians must balance the rarity and incompleteness of current reports against clear documentation that hepatic adverse events—including severe hepatitis—have occurred after ivermectin in individual cases and in spontaneous reports, and prioritize controlled studies and detailed case‑series with standardized causality assessment to move from signal to certainty (p1_s3; [4]/p1_s6).