[Kava, kavapyrones and toxic liver injury]

Area of Science:

• Phytomedicine
• Pharmacovigilance
• Hepatology

Background:

• Kava extracts from Piper methysticum are used as herbal anxiolytics.
• Recommended doses are 60-120 mg kavapyrones daily for up to 3 months.
• Patients often exceed recommended dosages and duration, perceiving herbal remedies as universally safe.

Purpose of the Study:

• To investigate suspected hepatotoxic reactions associated with kava extract therapy.
• To identify risk factors contributing to kava-induced liver injury.
• To propose preventive measures for minimizing hepatotoxic risks.

Main Methods:

• Analysis of patient data regarding kava dosage, duration of use, and co-medications.
• Review of reported adverse events, including hepatotoxicity.
• Identification of potential contributing factors like genetic polymorphisms (CYP2D6) and polypharmacy.

Main Results:

• Approximately 80% of patients exceeded recommended kavapyrones dosage (up to 480 mg/d) and/or duration (up to 2 years).
• Co-medication with other potentially hepatotoxic drugs and CYP2D6 deficiency were identified as additional risk factors.
• Seven patients experienced severe liver injury, including cases requiring liver transplantation and fatal outcomes, linked to overdose and prolonged kava use.

Conclusions:

• Kava extracts can pose significant hepatotoxic risks, particularly with overdose and prolonged use.
• Strict adherence to physician-prescribed limits (max 120-210 mg/day for 1-2 months) is essential.
• Medical supervision, regular liver function tests (ALT, gamma-GT), avoidance of co-medications and alcohol are recommended to mitigate risks.