Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus, elevated bile acids, and, specifically, elevated disulphated progesterone metabolites. We aimed to study changes in these parameters during treatment with dexamethasone or ursodeoxycholic acid (UDCA) in 40 out of 130 women included in the Swedish ICP intervention trial (26 randomized to placebo or UDCA, 14 randomized to dexamethasone). Serum bile acid profiles and urinary steroid hormone metabolites were analyzed using isotope-dilution gas chromatographymass spectrometry and electrospray-mass spectrometry. We found that all patients displayed ICP-typical serum bile acid profiles with >50% cholic acid at baseline but almost 80% UDCA upon treatment with this bile acid. In UDCA-treated patients, relative amounts of disulphated progesterone metabolites in urine decreased by 34%, 48% (P < 0.05), and 55% (P < 0.05) after 1, 2, and 3 weeks of treatment, respectively, which was significantly correlated to improvements of pruritus scores but not to serum bile acid levels. In contrast, in patients randomized to dexamethasone or placebo, no changes in steroid metabolites or pruritus scores were observed. Conclusion: UDCA treatment in ICP decreased urinary excretion of disulphated progesterone metabolites, suggesting that amelioration of pruritus is connected to stimulation of hepatobiliary excretion of progesterone disulphates. I ntrahepatic cholestasis of pregnancy (ICP) is a liver disease of as yet undefined etiology and pathogenesis. ICP is characterized by pruritus and elevated serum bile acids (Ն10 mol/L) with onset in the second half of pregnancy and persisting until delivery. 1 In the observational study of the Swedish ICP intervention trial, 2 the prevalence of pruritus in pregnancy was 2.1%, and that of ICP was 1.5%. Fetal complication rates were related to maternal serum bile acid levels and increased when bile acid levels exceeded 40 mol/L. 2 In the double-blind, placebo-controlled intervention study of the Swedish ICP trial, 3 effects of treatment with dexamethasone, ursodeoxycholic acid (UDCA), or placebo were investigated in 130 patients. UDCA but not dexamethasone significantly reduced alanine aminotransferase and bilirubin in the entire study group and improved pruritus and serum bile acid levels in women presenting with the severe form of ICP with bile acids Ն40 mol/L. 3 Compared with other liver diseases during pregnancy and normal pregnancies, women with ICP have a predominance of cholic acid (CA) among serum bile acids, and specifically, increased levels of steroid monosulphates and disulphates (predominantly progesterone metabolites) in serum and urine (reviewed by Reyes and Sjovall 4 ). Meng and coworkers showed that treatment with UDCA not only lowered plasma bile acid levels but also the levels of sulphated progesterone metabolites, possibly by increasing their hepatobiliary excretion. 5,6 To validate these findings in the Swedish ICP intervention trial population, we analyzed the

Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.

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