Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: A population-based cohort study

Authors

  • Hanns-Ulrich Marschall,

    Corresponding author
    • Sahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
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  • Elisabeth Wikström Shemer,

    1. Department of Obstetrics and Gynaecology and Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
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  • Jonas F. Ludvigsson,

    1. Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm
    2. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
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  • Olof Stephansson

    1. Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm
    2. Department of Women's and Children's Health, Karolinska University Hospital and Institutet, Stockholm, Sweden
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  • Potential conflict of interest: Nothing to report.

  • Supported by the Swedish Society of Medicine (to H.U.M., J.F.L., and O.S.), the Swedish Research Council – Medicine (K2005-72X-04793-30A, to H.U.M.; 522-2A09-195, to J.F.L.), the Fulbright Commission (to J.F.L.), and the regional research councils – ALF (to H.U.M. and O.S.).

Address reprint requests to: Hanns-Ulrich Marschall, M.D., Ph.D., Professor of Clinical Hepatology, Sahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, S-41345 Gothenburg, Sweden. E-mail: hanns-ulrich.marschall@gu.se; fax: +46-31-827458.

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. We aimed to estimate the risk of developing hepatobiliary disease in women with ICP and the odds of developing ICP in women with prevalent hepatobiliary disease. We analyzed data of women with births between 1973 and 2009 and registered in the Swedish Medical Birth Register. By linkage with the Swedish Patient Register, we identified 11,388 women with ICP who were matched to 113,893 women without this diagnosis. Diagnoses of preexisting or later hepatobiliary disease were obtained from the Patient Register. Main outcome measures were hazard ratios (HRs) for later hepatobiliary disease in women with ICP and odds ratios (ORs) for developing ICP in preexisting hepatobiliary disease. Risk estimates were calculated through Cox and logistic regression analyses. Women with ICP were more often diagnosed with later hepatobiliary disease (HR 2.62; 95% confidence interval [CI] 2.47-2.77; increment at 1% per year), hepatitis C or chronic hepatitis (HR 4.16; 3.14-5.51 and 5.96; 3.43-10.33, respectively), fibrosis/cirrhosis (HR 5.11; 3.29-7.96), gallstone disease or cholangitis (HR 2.72; 2.55-2.91, and 4.22; 3.13-5.69, respectively) as compared to women without ICP (P < 0.001 for all HRs). Later ICP was more common in women with prepregnancy hepatitis C (OR 5.76; 1.30-25.44; P = 0.021), chronic hepatitis (OR 8.66; 1.05-71.48; P = 0.045), and gallstone disease (OR 3.29; 2.02-5.36; P < 0.0001). Conclusion: Women with ICP have substantially increased risk for later hepatobiliary disease. Beyond gallstone-related morbidity we found a strong positive association between ICP and hepatitis C both before and after ICP diagnosis. Thus, we advocate testing for hepatitis C in women with ICP, in particular, since this potentially life-threatening infection can be treated successfully in the majority of patients. (Hepatology 2013;58:1385–1391)

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