title: Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy.
abstract: OBJECTIVE
  Intrahepatic cholestasis of pregnancy (ICP) is defined by pruritus, elevated total fasting serum bile salts (TBS) and transaminases, and an increased risk of adverse fetal outcome. An accurate diagnostic marker is needed. Increased serum autotaxin correlates with cholestasis-associated pruritus. We aimed at unraveling the diagnostic accuracy of autotaxin in ICP.
  
  
  METHODS
  Serum samples and placental tissue were collected from 44 women with uncomplicated pregnancies and 105 with pruritus and/or elevated serum transaminases. Autotaxin serum levels were quantified enzymatically and by Western blotting, autotaxin gene expression by quantitative PCR.
  
  
  RESULTS
  Serum autotaxin was increased in ICP (mean ± SD: 43.5 ± 18.2 nmol ml(-1)min(-1), n=55, p<0.0001) compared to other pruritic disorders of pregnancy (16.8 ± 6.7 nmol ml(-1)min(-1), n=33), pre-eclampsia complicated by HELLP-syndrome (16.8 ± 8.9 nmol ml(-1)min(-1), n=17), and pregnant controls (19.6 ± 5.7 nmol ml(-1)min(-1), n=44). Longitudinal analysis during pregnancy revealed a marked rise in serum autotaxin with onset of ICP-related pruritus. Serum autotaxin was increased in women taking oral contraceptives. Increased serum autotaxin during ICP was not associated with increased autotaxin mRNA in placenta. With a cut-off value of 27.0 nmol ml(-1)min(-1), autotaxin had an excellent sensitivity and specificity in distinguishing ICP from other pruritic disorders or pre-eclampsia/HELLP-syndrome. Serum autotaxin displayed no circadian rhythm and was not influenced by food intake.
  
  
  CONCLUSIONS
  Increased serum autotaxin activity represents a highly sensitive, specific and robust diagnostic marker of ICP, distinguishing ICP from other pruritic disorders of pregnancy and pregnancy-related liver diseases. Pregnancy and oral contraception increase serum autotaxin to a much lesser extent than ICP.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Medicine I, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kremer
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Bolier
authors.affiliation: Maternal and Fetal Disease Group, Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Dixon
authors.affiliation: Maternal and Fetal Disease Group, Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Geenes
authors.affiliation: Maternal and Fetal Disease Group, Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chambers
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Tolenaars
authors.affiliation: Women's and Children's Clinic, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carrie
authors.initials: C
authors.lastname: Ris-Stalpers
authors.affiliation: Deutsches Herzzentrum, Technische Universität, Munich, Germany.
authors.forename: Bernhard M
authors.initials: BM
authors.lastname: Kaess
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany; Department of Internal Medicine I, Hospital Barmherzige Brüder Munich, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rust
authors.affiliation: Women's and Children's Clinic, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joris A
authors.initials: JA
authors.lastname: van der Post
authors.affiliation: Maternal and Fetal Disease Group, Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Hepatology & Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: r.p.oude-elferink@amc.uva.nl.
authors.forename: Ronald P J
authors.initials: RP
authors.lastname: Oude Elferink
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000150:complications / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000235:genetics; D011537:Pruritus / Q000097:blood / Q000209:etiology; D012680:Sensitivity and Specificity; D000637:Transaminases / Q000097:blood; D000099189:Lysophospholipase D
chemical_list: D015415:Biomarkers; D010727:Phosphoric Diester Hydrolases; D000637:Transaminases; D000099189:Lysophospholipase D
keywords: Autotaxin; Bile salts; Cholestasis; Pregnancy; Pruritus