- 作者：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
- 关键词：AL ; acetyllycopsamine ; ALP ; alkaline phosphatase ; ALT ; alanine transaminase ; AST ; aspartate transaminase ; DDT ; dichlorodiphenyldichloroethylene ; EHNRI ; Ethiopian Health and Nutrition Research Institute ; ELISA ; Enzyme Linked Immunosorbent Assay ; GGT ; gamma glutamyl transferase ; H&E ; haematoxylin and eosin ; HVLD ; Hirmi Valley liver disease ; PA ; pyrrolizidine alkaloid ; THB ; Tigray Health Bureau ; ULN ; upper limit of normal of the laboratory reference range ; UPLC-MS ; Ultra performance liquid chromato
- 刊名：Journal of Hepatology
- 出版年：January, 2014
- 年：2014
- 卷：60
- 期：1
- 页码：96-102
- 全文大小：1596 K
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 脳 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.