Hepatotoxicity
The frequency of adverse reactions to kava, particularly liver injury, is not known. Based upon reported cases, the estimated frequency of clinically apparent liver injury due to kava is less than 1:1,000,000 daily doses. However, spontaneous reporting is believed to capture less than 1% of severe adverse events from the use of dietary supplements. Between 50 and 100 cases of clinically apparent liver injury have been published or discussed in the literature. Advocates of the herbal have strongly rejected these numbers, disputing both their accuracy and the causality assessment process. Still, there seem to be convincing evidence in some cases of severe hepatitis ending in fulminant hepatic failure, requiring liver transplantation, and even leading to death. Patients typically present with fatigue, nausea, elevations in serum aminotransferase levels, and jaundice 2 to 24 weeks after starting use of the product. The pattern of enzyme elevations is hepatocellular with marked elevations in serum aminotransferase and minimal increases in alkaline phosphatase levels. In some cases, features of immunoallergic hepatitis (rash, fever, eosinophilia, and recurrence on reexposure) are present. Liver biopsy findings include focal hepatocellular necrosis, lobular inflammation and intrahepatic cholestasis. In more severe cases there is massive or submassive necrosis.