TY - JOUR
T1 - Autotaxin Activity has a high Accuracy to diagnose Intrahepatic Cholestasis of Pregnancy
AU - Kremer, Andreas E
AU - Bolier, Ruth
AU - Dixon, Peter H
AU - Geenes, Victoria
AU - Chambers, Jenny
AU - Tolenaars, Dagmar
AU - Ris-Stalpers, Carrie
AU - Kaess, Bernhard M
AU - Rust, Christian
AU - van der Post, Joris A
AU - Williamson, Catherine
AU - Beuers, Ulrich
AU - Oude Elferink, Ronald P J
PY - 2015/4
Y1 - 2015/4
N2 - BACKGROUND&AIMS: 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 to unravel 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±18.2nmolmL(-1)min(-1), n=55,p<0.0001) compared to other pruritic disorders of pregnancy (16.8±6.7nmolmL(-1)min(-1), n=33), pre-eclampsia complicated by HELLP-syndrome (16.8±8.9nmolmL(-1)min(-1), n=17), and pregnant controls (19.6±5.7nmolmL(-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 27.0nmolmL(-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.
AB - BACKGROUND&AIMS: 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 to unravel 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±18.2nmolmL(-1)min(-1), n=55,p<0.0001) compared to other pruritic disorders of pregnancy (16.8±6.7nmolmL(-1)min(-1), n=33), pre-eclampsia complicated by HELLP-syndrome (16.8±8.9nmolmL(-1)min(-1), n=17), and pregnant controls (19.6±5.7nmolmL(-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 27.0nmolmL(-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.
U2 - 10.1016/j.jhep.2014.10.041
DO - 10.1016/j.jhep.2014.10.041
M3 - Article
C2 - 25450205
SN - 0168-8278
VL - 62
SP - 897
EP - 904
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -