What clinical evidence links ivermectin to elevated liver enzymes or liver injury?

1. What the clinical trial and regulatory literature actually shows

Randomized and controlled ivermectin trials—many conducted during the COVID‑19 era—reported serum aminotransferase elevations among participants, but these elevations occurred at similar rates in ivermectin and comparator/placebo arms; LiverTox (NCBI) concludes ivermectin is a "possible rare cause of mild clinically apparent liver injury" (likelihood score D) and notes isolated cases of clinically apparent injury in the literature ^[1]. Pharmacokinetic escalation studies found modest enzyme rises in small numbers (2 of 30 subjects at 30 mg had >2× ALT and GGT baseline), while higher doses up to 60 mg did not uniformly increase risk in those studies ^[4].

2. Case reports and biopsy‑confirmed DILI: the strongest clinical signal

The clearest, most detailed clinical evidence comes from case reports: a 2023 South African report described a 70‑year‑old who developed jaundice and marked enzyme elevations about three weeks after taking ivermectin for COVID‑19 prophylaxis; liver biopsy showed portal and lobular inflammation, bile duct injury and cholestasis, and the authors calculated a RUCAM score of 8 (highly probable causality) ^{[2] [3]}. Earlier single‑case reports exist (including a 2006 Loa loa case cited in reviews), and postmarketing surveillance notes hepatitis and elevated bilirubin have been reported ^{[1] [5]}.

3. Frequency and severity: common vs. rare, mild vs. serious

Summarizing regulatory and review sources: mild, self‑limited aminotransferase elevations are the most commonly reported hepatic effect; clinically apparent, severe DILI is described but rare. LiverTox cites single‑dose aminotransferase abnormalities and very rare clinically apparent cases; larger pharmacovigilance analyses and reviews characterize hepatotoxicity as "exceedingly rare" though they flag isolated severe events during the COVID‑19 era ^{[1] [6]}. Postmarketing databases and drug monographs list elevated ALT/AST and, less commonly, hepatitis or elevated bilirubin among reported adverse events ^[5].

4. Patterns of injury and clinical course when DILI occurs

When biopsy or histology was reported, the pattern has included mixed hepatocellular and cholestatic injury with portal triaditis, interface hepatitis and cholestasis; clinical courses in reported cases ranged from recovery after withdrawal (sometimes with steroids) to severe liver failure in scenarios involving overdose or misuse ^{[2] [7] [8]}. In the South African case, enzymes declined over weeks and normalized by three months after stopping ivermectin and a steroid taper ^[2].

5. Contributing factors, doses, and context that matter

Available sources note higher risk contexts include off‑label or prolonged use, self‑administration of veterinary formulations (overdose), polypharmacy during COVID‑19 (concurrent hepatotoxic drugs), and pre‑existing liver disease; pharmacovigilance analyses recommend monitoring liver enzymes in patients with liver disease ^{[4] [1] [2]}. Animal and experimental studies sometimes show conflicting hepatic effects—some preclinical work explores protective or anti‑fibrotic effects of ivermectin in models, underscoring biological complexity ^{[9] [3]}.

6. How authorities and drug references frame the risk

Drug references and safety summaries (LiverTox, drugs.com, Healthline summary based on labels) list hepatic events including elevated ALT/AST, bilirubin, and hepatitis in postmarketing experience, and advise monitoring and caution in patients with pre‑existing liver disease ^{[1] [5] [10]}. Reviews published during the COVID‑19 era emphasize that hepatotoxicity was rare but documented, and urge careful evaluation when ivermectin is used outside approved indications ^{[6] [4]}.

7. Bottom line and practical implications for clinicians and patients

Clinical evidence supports that ivermectin can cause transient elevations in liver enzymes in some patients and that rare, biopsy‑documented DILI has occurred with probable causality (RUCAM 8) — therefore clinicians should monitor liver tests when using ivermectin in higher‑risk situations or off‑label regimens, and counsel patients against unsupervised or veterinary dosing ^{[1] [2] [5]}. Available sources do not mention large, controlled signals of frequent severe hepatotoxicity attributable to standard single‑dose antiparasitic use ^[1].

Limitations: reporting is dominated by case reports, pharmacovigilance data and small trials; there is no large prospective safety database specifically powered to quantify rare severe DILI from ivermectin in diverse clinical settings in the provided sources (not found in current reporting).