What are the effects of Ivermectin on the liver?

From the Guidelines

Ivermectin is generally well-tolerated, but it can potentially affect the liver, particularly with higher doses or prolonged use, as evidenced by its metabolism through the cytochrome P450 system in the liver 1. When considering the effects of ivermectin on the liver, it's crucial to weigh the potential benefits against the risks, especially in patients with pre-existing liver conditions. The liver's role in metabolizing ivermectin suggests that monitoring liver function is essential, particularly for those on long-term therapy or with underlying liver disease. Some key points to consider include:

• Ivermectin's anti-inflammatory effects, as noted in in vitro and in vivo studies, may have implications for its use in conditions like COVID-19, but its impact on the liver must be carefully managed 1.
• The risk of liver toxicity increases with higher doses or prolonged use beyond recommended treatment durations, underscoring the need for cautious prescribing practices.
• Patients should be aware of symptoms that could indicate liver problems, such as yellowing of the skin or eyes, dark urine, persistent nausea, abdominal pain, or unusual fatigue, and seek medical attention if these occur.
• Regular liver function monitoring is advisable for patients on long-term ivermectin therapy or those with underlying liver conditions to mitigate potential liver effects. Given the information available, particularly from the most recent and highest quality study 1, it's clear that while ivermectin can be a valuable therapeutic agent, its potential effects on the liver must be carefully considered and managed to ensure patient safety and optimal outcomes.

From the FDA Drug Label

Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. The liver plays a role in the metabolism of ivermectin, but there is no direct information on the effects of ivermectin on the liver.

• The drug label does not provide information on liver toxicity or hepatotoxicity.
• Key points:
  • Ivermectin is metabolized by the liver.
  • No direct information on liver effects is available. 2 2

From the Research

Ivermectin Effects on the Liver

• The use of ivermectin has been associated with hepatic disorders, including hepatitis, hepatocellular injury, and cholestasis 3.
• A case report described a patient who developed jaundice and liver injury after initiating ivermectin for COVID-19 prevention, with liver histology showing a pattern of injury that was both portal and lobular 4.
• In vitro studies have shown that ivermectin can be cytotoxic to HepG2 cells, inducing damage to the cell membrane and decreasing mitochondrial membrane potential, with oxidative damage involved in the toxicity 5.
• The safety of ivermectin, particularly with regards to hepatic disorders, should be studied more exhaustively, especially when used for COVID-19 treatment 3.
• Some studies suggest that antioxidants, such as tetrahydrocurcumin and vitamin C, may mitigate the toxic effects of ivermectin on the liver 5.

Mechanisms of Ivermectin-Induced Liver Injury

• Ivermectin has been shown to decrease cellular adenosine triphosphate levels and stimulate the production of reactive oxygen and nitrogen species (RONS) in HepG2 cells 5.
• The levels of reduced glutathione were decreased in a time- and dose-dependent manner, suggesting that oxidative stress may play a role in ivermectin-induced liver injury 5.

Clinical Implications

• The use of ivermectin for COVID-19 treatment or prevention should be carefully considered, particularly in patients with pre-existing liver conditions 3, 4.
• Further studies are needed to fully understand the effects of ivermectin on the liver and to determine the safest and most effective treatment regimens 3, 5.