Toxic Hepatitis After Consumption of Traditional Kava Preparation

Abstract

Liver toxicity from the use of kava dietary supplements has been reported, but little is known about the side effects of traditional kava preparations. We present a case study of a tourist who developed serious toxic liver disease after consumption of kava beverages in traditional Samoan kava ceremonies.

Case report

A 42‐year‐old previously healthy white male presented with weakness, loss of appetite, and jaundice. He did not report specific organ symptoms, and there was no history of liver disease. He admitted alcohol consumption of not more than one drink daily but denied medication or drug use. He also had no contact with hazardous substances at work. Three weeks before, he had returned from a 20‐day honeymoon that he and his wife spent on the Samoan islands.

His physical status was weak, with normal nutrition status. Body temperature was normal. There was scleral and skin jaundice; the liver was of normal size but with some pain on pressure. Further physical examinations were unremarkable.

Laboratory tests showed markedly elevated liver enzymes (aspartate aminotransferase, 1,602 U/L; alanine aminotransferase, 2,841 U/L; gamma‐glutamyl transpeptidase, 121 U/L; alkaline phosphatase, 285 U/L), lactate dehydrogenase (460 U/L), and bilirubin (9.3 mg/dL). All other routine parameters including coagulation tests, blood cell counts, and protein electrophoresis were in the normal range. Serum ferritin was elevated (1,531 μg/L), ceruloplasmin was normal, and urine copper excretion was slightly increased. Serologic tests for viral hepatitis including anti‐hepatitis A virus immunoglobulin ( Ig) M, hepatitis B surface antigen, anti‐hepatitis B core antigen (HBc) IgM, anti‐HBc IgG, anti‐hepatitis C virus (HCV), HCV RNA, cytomegalovirus IgM, Epstein–Barr virus IgM, and for autoimmune liver disease (antinuclear antibodies, anti‐smooth muscle, anti‐liver‐kidney microsomal, anti‐soluble liver antigen, antimitochondrial antibodies) were negative. Genetic testing was negative for hemochromatosis.

Abdominal ultrasound showed a hyperechoic liver structure with normal biliary ducts and a multilayer aspect of the gallbladder. There was a single 15 mm lymph node in the portal area. A liver puncture was performed. Histologic slides showed a pattern that was compatible with toxic liver injury. There was an infiltration of the portal fields with lymphocytes and eosinophilic granulocytes, necrosis of single or clustered hepatocytes, and swollen Kupffer cells. Fatty liver disease was not present.

Because the available information at this stage did not provide a satisfactory explanation for the disease, the patient was again interviewed with a particular focus on drug consumption. Finally, he admitted that during his stay in Samoa, he had repeatedly participated in kava ceremonies and consumed a cumulative volume of 2 to 3 L of traditional kava preparations. We therefore diagnosed a kava‐induced toxic hepatitis.

The status of the patient initially deteriorated, with bilirubin rising to a maximum of 31 mg/dL, although aminotransferases were already falling (Figure 1). The patient initially refused oral intake, so he received intravenous glucose infusions and meanwhile, with increasing prothrombin time, vitamin K. Later, oral nutritional supplements could be introduced and normal nutrition was reestablished. With improving physical status and falling bilirubin levels, the patient was discharged 19 days after admission. After 36 days, he completely recovered based on ultrasonographic scans and laboratory tests that normalized.

Figure 1

Time‐course of kava intake (exposition) and laboratory changes. (▪) Bilirubin (mg/dL); (□) Alanine aminotransferase (U/L).

Discussion

Kava beverages are a traditional remedy consumed by the population of many South Pacific islands and by Australian Aborigines. It is obtained from the roots of a pepper plant (Piper methysticum), which are ground, combined with water, filtered, and consumed as aqueous emulsions. The psychotropic effect is reported to be more balancing and tranquilizing than exciting. The plant‐derived beverage is traditionally consumed in ritual kava ceremonies, which may be open to visitors and tourists. In travel reports and guidebooks, attending such ceremonies with consumption of kava preparations is appreciated as a folkloristic event that tourists should not miss.

Because of the known mood‐altering effects, kava was introduced into western herbal medicine for treatment of anxiety and insomnia. ¹ For this purpose, mainly alcoholic and acetonic extracts, kavapyrones or kavalactones, were marketed. However, in the following years, an increasing number of toxic hepatitis cases were reported. ^2,3 Liver transplantation became necessary for a few patients, and there were also fatal outcomes. ^4,5 As a consequence, health authorities in Germany and some other countries banned kava‐containing medical products.

The mechanism of kava toxicity is unclear. There is no definite dose dependency. A longer duration of treatment seems to increase risk, but there were also cases with severe liver disease after a few weeks’ treatment. ⁵ Therefore, idiosyncratic as well as immune allergic mechanisms are discussed. ⁶ A suspected influence of the mode of extraction has not been confirmed. Comedication and alcohol consumption had been potential cofactors in some of the reported patients. ⁶ In our case, there was little alcohol consumption as reported by the patient, so interactions with kava toxicity may or may not be possible. Certain genetic conditions involving the cytochrome P450 system may play a role, but this remains to be confirmed. ⁷

Little is known about toxicity of kava consumed in the traditional way as an aqueous suspension. In a study of regular kava consumers in an Australian Aboriginal community, elevated levels of gamma‐glutamyl transpeptidase and alkaline phosphatase were found in the majority of the study population. ^8–10 However, aminotransferases were normal in contrast to patients with kava hepatitis. Only a few reports of severe liver disease after traditional kava consumption are available. ¹¹ This suggests a low incidence, but characteristics of local populations and health systems may be responsible for underreporting. To our knowledge, no tourist to date has been reported with hepatitis after consumption of traditional kava beverages.

We could not definitely prove the causality of kava consumption for the hepatitis in our patient. This, however, is the case in almost all published cases, with the exception of two reports in which reexposition led to a relapse of hepatitis. ^3,5 As toxicity of kava is accepted and other potential causes were excluded, we believe that there is little doubt about causality in the presented case. When the Council for International Organizations of Medical Sciences score system for drug‐induced liver injury is used to analyze the data of our patient, a total score of 10 suggests that causality is highly probable. ¹²

This case demonstrates that kava toxicity, which has been reported among some kava dietary supplement users, may also occur with consumption of traditional kava preparations. Although the risk seems to be very small, it may not be correct to classify kava beverage consumption as a harmless touristic event. This information should be made available to tourists planning to travel South Pacific islands.

Declaration of interests

The authors state that they have no conflicts of interest.