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Robinson O, Want E, Coen M, et al. Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT. J Hepatol. 2013;60(1):96-102doi: 10.1016/j.jhep.2013.07.039.
Robinson, O., Want, E., Coen, M., Kennedy, R., van den Bosch, C., Gebrehawaria, Y., Kudo, H., Sadiq, F., Goldin, R. D., Hauser, M. L., Fenwick, A., Toledano, M. B., & Thursz, M. R. (2014). Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT. Journal of hepatology, 60(1), 96-102. https://doi.org/10.1016/j.jhep.2013.07.039
Robinson, Oliver, et al. "Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT." Journal of hepatology vol. 60,1 (2014): 96-102. doi: https://doi.org/10.1016/j.jhep.2013.07.039
Robinson O, Want E, Coen M, Kennedy R, van den Bosch C, Gebrehawaria Y, Kudo H, Sadiq F, Goldin RD, Hauser ML, Fenwick A, Toledano MB, Thursz MR. Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT. J Hepatol. 2014 Jan;60(1):96-102. doi: 10.1016/j.jhep.2013.07.039. Epub 2013 Aug 20. PMID: 23973933.
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J Hepatol. 2014 Jan;60(1):96-102. doi: 10.1016/j.jhep.2013.07.039. Epub 2013 Aug 20.

Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT.

Journal of hepatology

Oliver Robinson, Elizabeth Want, Muireann Coen, Ruth Kennedy, Catharina van den Bosch, Yohannes Gebrehawaria, Hiromi Kudo, Fouzia Sadiq, Robert D Goldin, Michael L Hauser, Alan Fenwick, Mireille B Toledano, Mark R Thursz

Affiliations

  1. School of Public Health, Imperial College London, UK; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
  2. Department of Surgery & Cancer, Imperial College London, UK.
  3. Abraham's Oasis, Shire, Ethiopia.
  4. Tigray Health Bureau, Mekele, Ethiopia.
  5. Department of Medicine, Imperial College London, UK.
  6. School of Public Health, Imperial College London, UK; Onehealth Foundation, Switzerland.
  7. School of Public Health, Imperial College London, UK.
  8. Department of Medicine, Imperial College London, UK. Electronic address: [email protected].

PMID: 23973933 DOI: 10.1016/j.jhep.2013.07.039

Abstract

BACKGROUND & AIMS: Hirmi Valley liver disease was first reported in 2001 in Tigray, Ethiopia. 591 cases, including 228 deaths, were reported up to December 2009. The pyrrolizidine alkaloid acetyllycopsamine was detected in stored grain and residents reported adding the pesticide DDT (dichlorodiphenyldichloroethylene) directly to their food stores. We aimed to characterise the clinical features of the disease, and explore the role of these chemicals in its aetiology.

METHODS: 32 cases were examined and full clinical histories taken. Nine cases underwent liver biopsy in hospitals. Serum and urine samples were collected from cases and controls. Urine was analysed for acetyllycopsamine by UPLC-MS. Total DDT in serum was measured by ELISA. Hepatotoxicity of DDT and acetyllycopsamine alone or in combination was explored in C57BL/6J mice.

RESULTS: Clinical presentation included epigastric pain, abdominal swelling, bloody diarrhoea, hepatomegaly, splenomegaly, and ascites. Histology revealed acute injury characterised by centrilobular necrosis or chronic injury with bile ductular reaction, cytomegaly and fibrosis but no hepatic vein occlusion. Acetyllycopsamine was detected in urine samples taken in the affected area with significantly greater concentrations in 45 cases than in 43 controls (p=0.02). High levels of DDT (>125 ppb) were detected in 78% of serum samples. In mice, DDT (3 × 75 mg/kg) significantly increased the hepatotoxicity (plasma ALT, p=0.0065) of acetyllycopsamine (750 mg/kg), and in combination induced liver pathology similar to Hirmi Valley liver disease including centrilobular necrosis and cytomegaly.

CONCLUSIONS: This novel form of disease appears to be caused by co-exposure to acetyllycopsamine and DDT.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords: AL; ALP; ALT; AST; Acetyllycopsamine; DDT; EHNRI; ELISA; Enzyme Linked Immunosorbent Assay; Ethiopia; Ethiopian Health and Nutrition Research Institute; GGT; H&E; HVLD; Hepatotoxicity; Hirmi Valley liver disease; PA; THB; Tigray Health Bureau; ULN; UPLC-MS; Ultra performance liquid chromatography – mass spectroscopy; VOD; acetyllycopsamine; alanine transaminase; alkaline phosphatase; aspartate transaminase; cyp3a; dichlorodiphenyldichloroethylene; gamma glutamyl transferase; haematoxylin and eosin; pyrrolizidine alkaloid; upper limit of normal of the laboratory reference range; veno-occlusive disease

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