German authors analysed 29 novel cases of hepatitis associated with Piper methysticum ingestion, which occurred between 1990 and 2002, in addition to seven published case reports using a clinical diagnostic scale established for adverse hepatic drug reactions. Hepatic necrosis or cholestatic hepatitis was noticed with both alcoholic and acetonic P. methysticum extracts. The majority of the 29 patients and the additional seven published reports were women (27 females, nine males). Both the cumulative dose and the latency to when the hepatotoxic reaction emerged were highly variable. Nine patients developed fulminant liver failure, of which eight patients underwent liver transplantation. Three patients died, two following unsuccessful liver transplantation and one without. In all other patients, a complete recovery was noticed after the withdrawal of P. methysticum. Pathophysiologically, both immuno-allergic and idiosyncratic factors may be responsible.