[e-drug] Kava Kava (3)

[Beverley Snell <bev@burnet.edu.au>]

E-drug: Kava Kava (3)
------------------------------------------------------------


Larry,
Here are 2 references in German and a whole article from the 
BMJ that was available free to download.  The other cited 
references look interesting too.   Kava is well known in this part of 
the world.
Beverley Snell

1: Kraft M, Spahn TW, Menzel J, Senninger N, Dietl KH, Herbst H, 
Domschke W, Lerch MM.  [Fulminant liver failure after 
administration of the herbal antidepressant Kava-Kava].  Dtsch Med 
Wochenschr. 2001 Sep 7;126(36):970-2. German.

2: Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis 
after taking herbal remedies].  Dtsch Med Wochenschr. 1998 Nov 
20;  123 (47):1410-4. German.

BMJ 2001;322:139 ( 20 January )
Drug points
Hepatitis associated with Kava, a herbal remedy for anxiety
Monica Escher, Jules Desmeules.
Division of Clinical Pharmacology and Toxicology
Emile Giostra.
Division of Gastroenterology
Gilles Mentha.
Division of Visceral Surgery, Geneva University Hospital, 1211 Geneva 
14, Switzerland

Kava, the rhizome of the pepper plant Piper methysticum, has been 
widely used in the South Pacific as a narcotic drink. Lactones, the 
major constituents of kava, are considered to be pharmacologically 
active and are sold in Europe and the United States as standardised 
extracts for anxiety and tension. 

A 50 year old man presented to his doctor because of jaundice. He 
had noticed fatigue for a month, a "tanned" skin, and dark urine. The 
medical history was unremarkable apart from slight anxiety, for 
which he had been taking three to four capsules of kava extracts 
daily for two months (maximum recommended dose three capsules) 
corresponding to a dose of 210-280 mg lactones (Laitain, Schwabe, 
Switzerland). He took no other drugs and did not consume alcohol. 
Liver function tests showed a 60-fold and 70-fold increase in 
aspartate aminotransferase and alanine aminotransferase 
concentrations, respectively. Alkaline phosphatase concentration 
was 430 IU/l (normal range 30-125), -glutamyltransferase 691 IU/l 
(9-35), lactate dehydrogenase 1132 IU/l (125-240), and total and 
conjugated bilirubin 279.2 =B5mol/l (6.8-25) and 212.3 =B5mol/l 
(1.7-8.6), respectively. Prothrombin time was 25%. The patient was 
admitted to hospital.

Ultrasonography showed a slight increase in liver size but no 
ascites or portal vein thrombosis. Blood tests for hepatitis A, B, C, 
and E, HIV, cytomegalovirus, and Epstein-Barr virus gave negative 
results. The patient's condition deteriorated within 48 hours. He 
developed stage IV encephalopathy and had to be intubated. 
Prothrombin time was then 10%. The patient received a liver 
transplant two days later. He recovered uneventfully. On 
examination the liver was atrophic, and the subhepatic and portal 
veins were free. Histology showed extensive and severe 
hepatocellular necrosis and extensive lobular and portal infiltration 
of lymphocytes and numerous eosinophils.

Heavy consumption of kava has been associated with increased 
concentrations of -glutamyltransferase, suggesting potential 
hepatotoxicity.1 A case of recurring necrotising hepatitis has been 
reported.2 In our patient a relation between ingestion of kava and 
fulminant hepatic failure is supported by the chronology, 
histological findings, and exclusion of other causes of hepatitis. 
Assessment of causality according to the definitions of the World 
Health Organization is probable. Acute liver failure with a fatal 
outcome or that necessitates liver transplant has been attributed to 
various herbal preparations.3-5 This case illustrates the importance 
of inquiring about the use of over the counter health products. It 
was reported to the Swiss Pharmacovigilance Center in Berne.

References
1.  Mathews JD, Riley MD, Fejo L, Munoz E, Milns N, Gardner ID, et 
al.  Effects of the heavy usage of kava on physical health: summary 
of a pilot survey in an Aboriginal community. Med J Aust 1988; 148: 
548-555
2.  Strahl S, Ehret V, Dahm HH, Maier KP. Necrotizing hepatitis 
after taking herbal medication. Dtsch Med Wschr 1998; 123: 
1410-1414[Medline]. (In     German.)  
3.  Mostefa-Kara N, Pauwels A, Pines E, Biour M, Levy VG. Fatal 
hepatitis after herbal tea. Lancet 1992; 340: 674[Medline].
4.  Yoshida EM, McLean CA, Cheng ES, Blanc PD, Somberg KA, 
Ferrell LD, et al. Chinese herbal medicine, fulminant hepatitis, and 
liver transplantation.  Am J Gastroenterol 1996; 91: 2647-2648
5.  Sheikh NM, Philen RM, Love LA. Chaparral-associated 
hepatotoxicity. Arch Intern Med 1997; 157: 913-919.

Beverley Snell
International Health Unit
Macfarlane Burnet Institute for Medical Research & Public Health
P O Box 254 Fairfield Vic Australia 3078
Telephone 613 9282 2115 / 9282 2275
Fax 613 9482 3123
Time zone: 11 hours ahead of GMT.
email <bev@burnet.edu.au>

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