Successful Liver Transplantation for Kava-Associated Liver Failure: Report of 2 Cases

Abstract

The use of herbal medicines dates back to 2100 BC and in the United States (US) herbal and dietary supplements (HDS) represent a 180 billion dollar market. Kava is an herbal preparation used as alternative medicine for anxiety and depression. We present two cases of fulminant hepatic failure (FHF) associated with kava ingestion. A 46 year old Caucasian female was transferred with acute liver failure and two weeks of a non-productive cough, fatigue, nausea, epigastric pain and jaundice. Laboratory studies were notable for an aspartate aminotransferase (AST) of 3830 (U/L), alanine aminotransferase (ALT) of 2385 (U/L), alkaline phosphatase (ALP) of 306 (U/L), bilirubin of 10.3 (mg/dL) and an international normalized ratio (INR) of 1.83. The culprit was thought to be daily kava use started three months prior. By hospital day three she had acute fulminant liver failure with grade four coma and underwent an urgent orthotopic liver transplantation. Explant pathology showed extensive necrosis with associated hemorrhage and bile duct proliferation. At our same facility a 60 year old African American female was referred for elevated liver function tests with one month of fatigue, decreased appetite, weakness, fevers, dark urine, clay colored stools and jaundice. She endorsed use of over the counter Botanicalm (containing kava). Laboratory studies were notable for AST 1405 (U/L), ALT 1240 (U/L), ALP 323 (U/L), bilirubin 24 (mg/dL), and INR of 2.6. Liver biopsy revealed submassive/massive necrosis and despite being started on N-acetylcysteine and prednisone she required an urgent orthotopic liver transplantation on hospital day 12. Explant pathology showed submassive necrosis and changes suggestive of early fibrosis. Over the past 50 years 21 herbs and 12 dietary supplements were reported to pose a risk for liver injury. Kava is a traditional Pacific beverage made from the roots and stems of Piper methysticum. Historically it was reserved for ingestion by priests and chiefs. The mechanism for kava induced liver injury remains elusive but generally speaking it favors a mixed pattern of injury, predilection for females, and a variable dose and latency response. Patients with liver disease comprise a unique population at particular risk from HDS. Up to 40% of people admit to not disclosing their use of HDS to their physicians and kava ingestion is just one of many that can cause fulminant liver failure. Further research is needed.2183 Figure 1. Liver biopsy Case 1