Volume 60, Issue 1, Pages (January 2014)

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Volume 60, Issue 1, Pages 96-102 (January 2014) Hirmi Valley liver disease: A disease associated with exposure to pyrrolizidine alkaloids and DDT 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 Journal of Hepatology Volume 60, Issue 1, Pages 96-102 (January 2014) DOI: 10.1016/j.jhep.2013.07.039 Copyright © 2013 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Comparison of distribution of serum concentration of several biochemical clinical indicators between cases and controls. Black bar, median; box, interquartile range; whiskers, upper and lower values within 1.5 box lengths of the quartile values; dots, outliers. Journal of Hepatology 2014 60, 96-102DOI: (10.1016/j.jhep.2013.07.039) Copyright © 2013 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Patient histology. (A) Zone 3 necrosis and central vein. H&E, 200×. (B) Foci of swollen hepatocytes associated with prominent lipofuscin accumulation. H&E, 400×. (C) Widespread bile ductular reaction at the parenchymal interface but no bile duct loss. H&E, 100×. (D) Patent central vein. Chromotrope aniline blue, 100×. (E) Marked copper associated protein accumulation in periportal hepatocytes. Orcein, 400×. (F) Bridging fibrosis with portal – central bridging. Chromotrope aniline blue, 100×. Journal of Hepatology 2014 60, 96-102DOI: (10.1016/j.jhep.2013.07.039) Copyright © 2013 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Acetyllycopsamine (AL) relative concentration in urine. Black bar, median; box, interquartile range; whiskers, upper and lower values within 1.5 box lengths of the quartile values; dots, outliers; a.u., arbitrary units; left: N of cases=45; N of controls=42; N of Quality Control (QC) replicates=8; right: N of cases=45; N of controls=25; N of village controls=17. Journal of Hepatology 2014 60, 96-102DOI: (10.1016/j.jhep.2013.07.039) Copyright © 2013 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Toxicological testing in mice. (A) Mean fold change in cyp3a11 expression in DDT treated group compared to control group. (B) Mean plasma ALT activity in controls, DDT treated, AL treated and co-treatment of DDT and AL groups at 24h post-treatment. Error bars show standard error. (C–F) Mouse liver histology. Stained by H&E. (C) Normal liver, 24h after DDT only treatment, 100×. (D) Swollen hepatocytes, 24h after DDT and AL (750mg/kg) treatment, 200×. (E) Zone 3 necrosis, 24h after DDT and AL (750mg/kg) treatment, 100×. (F) Zone 3 necrosis, 24h after 1500mg/kg AL treatment, 100×. n.s., not significant. Journal of Hepatology 2014 60, 96-102DOI: (10.1016/j.jhep.2013.07.039) Copyright © 2013 European Association for the Study of the Liver Terms and Conditions