Correspondence

Severe, Acute Liver Injury and Khat Leaves

N Engl J Med 2010; 362:1642-1644April 29, 2010

Article

To the Editor:

The chewing of khat leaves (Catha edulis) is a widespread recreational custom in East Africa and the Arabian Peninsula. The plant contains the alkaloids cathine and cathinone, which have amphetamine-like properties and produce a variety of pleasurable effects. Khat is banned in the United States, but large quantities are nonetheless exported to North America from the United Kingdom, where it is freely available and used widely by immigrant populations. The detrimental personal and social effects of khat are well recognized.1 Both psychiatric illness2 and cardiovascular disease3 have been recorded. We report the results of our observations of six patients whose use of khat was associated with severe, acute hepatitis that resulted in death or liver transplantation (Table 1Table 1Characteristics of Six Patients with Khat-Related Liver Injury.). The patients presented over a 5-year period, and their cases were neither geographically nor temporally related.

Five of the patients had a history of previous unexplained hepatitis while they were living in the United Kingdom. All chewed khat and had been counseled against its use. However, all had resumed use before their second presentation. All six cases were thoroughly reviewed to rule out other causes of liver injury (Table 1). All had similar histopathological findings characterized by multilobular necrosis; two of them had a background of chronic liver disease. Five of the six patients underwent orthotopic liver transplantation, accounting for 10% of the patients in our unit who received transplants because of fulminant or subfulminant hepatic failure during this 5-year period.

A number of factors point to khat ingestion as the cause of the liver injury in these patients: no other cause for their liver disease was found, re-exposure to khat resulted in further liver damage, a high concentration of cathinone was identified in a sample of damaged liver tissue from one patient, khat-related hepatotoxicity has been demonstrated in animals,4 and the histopathologic changes in the liver mirror those induced in humans by ingestion of the drug ecstasy, another amphetamine-like compound.5 Evidence of chronic liver disease in two patients suggests that long-term use of khat may be associated with repeated episodes of subclinical hepatitis, with evolution to chronic liver disease over time.

The mechanism of khat-related hepatoxicity is unknown; there were no compelling features of an immunoallergic or autoimmune process, although both should be considered. A high concentration of cathinone was detected in the liver of a patient 3 weeks after the patient's last use of khat, suggesting that drug accumulation may be important. It is unlikely that the liver injury is related to contaminants such as herbicides, pesticides, heavy metals, or toxigenic fungi.

A high degree of suspicion is warranted when patients from ethnic communities where khat use is prevalent present with otherwise unexplained liver injury. They should be counseled against its use and supported in this endeavor.

Michael H. Chapman, M.D.
Mikio Kajihara, M.D., Ph.D.
University College London Medical School, London, United Kingdom

Gina Borges, Ph.D.
University of Glasgow, Glasgow, United Kingdom

James O'Beirne, M.D.
David Patch, M.D.
Amar P. Dhillon, M.D.
Royal Free Hampstead NHS Trust, London, United Kingdom

Alan Crozier, Ph.D.
University of Glasgow, Glasgow, United Kingdom

Marsha Y. Morgan, M.D.
University College London Medical School, London, United Kingdom
mymorgan@medsch.ucl.ac.uk

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

5 References

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Citing Articles (10)

Citing Articles

1. 1

   2012. Khat (Catha edulis (Vahl) Forsskal ex Endl.) and Cathinone. , 873-879.
   CrossRef

2. 2

   James H. Lewis, David E. Kleiner. 2012. Hepatic injury due to drugs, herbal compounds, chemicals and toxins. , 645-760.
   CrossRef

3. 3

   John M. Corkery, Fabrizio Schifano, Adenekan Oyefeso, A. Hamid Ghodse, Thomy Tonia, Vinesha Naidoo, Jennifer Button. (2011) ‘Bundle of fun’ or ‘bunch of problems’? Case series of khat-related deaths in the UK. Drugs: Education, Prevention, and Policy 18:6, 408-425
   CrossRef

4. 4

   Christopher O.C. Bellamy. (2011) Recent advances in medical liver disease. Diagnostic Histopathology 17:12, 548-556
   CrossRef

5. 5

   P. Roelandt, C. George, F. d'Heygere, R. Aerts, D. Monbaliu, W. Laleman, D. Cassiman, C. Verslype, W. van Steenbergen, J. Pirenne, A. Wilmer, F. Nevens. (2011) Acute Liver Failure Secondary to Khat (Catha edulis)–Induced Necrotic Hepatitis Requiring Liver Transplantation: Case Report. Transplantation Proceedings 43:9, 3493-3495
   CrossRef

6. 6

   Ian Webzell, David Ball, James Bell, Roy A. Sherwood, Andrew Marsh, John G. O'Grady, Nigel D. Heaton. (2011) Substance use by liver transplant candidates: An anonymous urinalysis study. Liver Transplantation 17:10, 1200-1204
   CrossRef

7. 7

   Endalkachew Admassie, Ephrem Engidawork. (2011) Subchronic administration of Catha edulis F. (khat) extract is marked by elevation of cardiac biomarkers and subendocardial necrosis besides blood pressure alteration in rats. Journal of Ethnopharmacology 136:1, 246-253
   CrossRef

8. 8

   Rogier J. L. Stuyt, Stefan M. Willems, Martin J. Wagtmans, Bart van Hoek. (2011) Chewing khat and chronic liver disease. Liver International 31:3, 434-436
   CrossRef

9. 9

   Thierry Coton, Fabrice Simon, Manuela Oliver, Philippe Kraemer. (2011) Hepatotoxicity of khat chewing. Liver International 31:3, 434-434
   CrossRef

10. 10

    A. Al-Motarreb, M. Al-Habori, K.J. Broadley. (2010) Khat chewing, cardiovascular diseases and other internal medical problems: The current situation and directions for future research. Journal of Ethnopharmacology 132:3, 540-548
    CrossRef