fax: +31-20-566 95 82
Autoimmune, Cholestatic and Biliary Disease
Article first published online: 4 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 4, pages 1391–1400, October 2012
How to Cite
Kremer, A. E., van Dijk, R., Leckie, P., Schaap, F. G., Kuiper, E. M.M., Mettang, T., Reiners, K. S., Raap, U., van Buuren, H. R., van Erpecum, K. J., Davies, N. A., Rust, C., Engert, A., Jalan, R., Oude Elferink, R. P.J. and Beuers, U. (2012), Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology, 56: 1391–1400. doi: 10.1002/hep.25748
Potential conflict of interest: A.E.K., R.O.E., and U.B. have filed a patent on autotaxin (WO 2011/049433 A1).
The authors thank Dr. J. Aoki (University of Tokyo, Tokyo, Japan) for kindly providing 4F1/autotaxin antibody and Dr. R. Hoekstra (University of Amsterdam, Amsterdam, The Netherlands) for generously providing HepG2 cells overexpressing pregnane X receptor.
- Issue published online: 4 OCT 2012
- Article first published online: 4 OCT 2012
- Accepted manuscript online: 2 APR 2012 12:51AM EST
- Manuscript Accepted: 24 MAR 2012
- Manuscript Received: 1 NOV 2011
- ZonMW TOP grant (to R.O.E.. Grant Number: TOP 40-00812-98-10054
- “Primary sclerosing cholangitis” from the Deutsche Crohn-Colitis-Vereinigung and the Norwegian Primary Sclerosing Cholangitis Foundation
- Deutsche Forschungsgemeinschaft (to A.E.K.. Grant Number: KR3618/1-1
Additional Supporting Information may be found in the online version of this article.
|HEP_25748_sm_SuppFig1.tif||420K||Supplementary Figure 1: ATX activity showed a linear correlation with the itch intensity represented on a VAS ranging from 0 (no pruritus) to 100 (unbearable pruritus). Pearson's correlation coefficient: r=0.45, p<0.0001.|
|HEP_25748_sm_SuppFig2.tif||1446K||Supplementary Figure 2: (A): Itch severity score (ISS) showed a linear correlation with the VAS in patients undergoing MARS therapy (Pearson's correlation coefficient: r=0.92, p<0.0001). (B): Improvement in ISS in patients responding (Responders) to MARS therapy. (C): No change in ISS was observed in Non-Responders. (D/E): Changes of itch intensity (ISS and VAS) and ATX activity after therapy (related to the pre-treatment value) showed a linear correlation (Pearson's correlation coefficient: ISS: r=0.71, p<0.01, VAS: r=0.61, p<0.03).|
|HEP_25748_sm_SuppFig3.tif||516K||Supplementary Figure 3: Change in total serum bile salt (TBS) levels and itch intensity during the course of nasobiliary drainage. After an initial drop on the first and second day of the intervention, TBS rose back to baseline values long before pruritus re-occurred in these patients.|
|HEP_25748_sm_SuppFig4.tif||696K||Supplementary Figure 4: Rifampicin induced CYP3A4 in a PXR-dependent manner. CPY3A4 gene expression tended to be increased (n=6; not significant) after incubation with 10 μM rifampicin for 24 hours (A). This induction was increased (p<0.01; n=3) in HepG2 cells overexpressing PXR (B), whereas it vanished in PXR knock-down cells, but not cells being transduced with scrambled shRNA (C).|
|HEP_25748_sm_SuppTab1.doc||44K||Supplementary Table 1: Characteristics and serum chemistry of cholestatic patients with and without pruritus. All values are expressed as means ± SD. P-values are for comparison between the subgroups of cholestatic patients with and without pruritus. Abbreviations: AP = alkaline phosphatase, γGT = γ-glutamyltransferase, TBS = total serum bile salts, ALT = alanine aminotransferase, AST = aspartate aminotransferase, CRP = C-reactive protein.|
|HEP_25748_sm_SuppTab2.doc||39K||Supplementary Table 2: Characteristics and serum chemistry of Hodgkin lymphoma patients with and without pruritus. All values are expressed as means ± SD. P-values are for comparison between the subgroups of patients with and without pruritus. Abbreviations: ESR = erythrocyte sedimentation rate, TBS = total serum bile salts.|
|HEP_25748_sm_SuppTab3.doc||42K||Supplementary Table 3: Characteristics and serum chemistry of uremic patients with and without pruritus. All values are expressed as means ± SD. P-values are for comparison between the subgroups of patients with and without pruritus. Abbreviations: PTH = parathyroid hormone, CRP = C-reactive protein, TBS = serum bile salts.|
|HEP_25748_sm_SuppTab4.doc||38K||Supplementary Table 4: Characteristics and serum chemistry of cholestatic patients undergoing MARS therapy. All values are expressed as means ± SD. P-values are for comparison between the subgroups of patients with and without pruritus. Abbreviations: AP = alkaline phosphatase, ALT = alanine aminotransferase, TBS = serum bile salts, INR = prothrombin time.|
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.