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Additional Supporting Information may be found in the online version of this article.

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HEP_25748_sm_SuppFig1.tif420KSupplementary 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.tif1446KSupplementary 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.tif516KSupplementary 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.tif696KSupplementary 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.doc44KSupplementary 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.doc39KSupplementary 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.doc42KSupplementary 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.doc38KSupplementary 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.

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