Advertisement

A model based on routine liver tests can reliably exclude intrahepatic cholestasis of pregnancy

      Highlights

      • A retrospective cohort study among 640 women evaluated for ICP.
      • In all women serum bile acids levels were tested along with routine liver tests.
      • A combined laboratory score incorporating AST, GGT, ALK and TB was shown to reliably exclude the diagnosis of ICP.
      • The current study findings may be particularly important as serum bile acids levels testing is not readily available.

      Abstract

      Objectives

      Serum bile acid (BA) levels testing is used for the diagnosis of intrahepatic cholestasis of pregnancy (ICP). We aimed to determine the performance of routine liver tests in the evaluation of ICP.

      Methods

      A retrospective cohort study conducted at a university hospital, including all pregnant women who underwent serum BA levels testing due to suspected ICP during 2007–2019. Liver tests were performed in all women including: aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALK), gamma-glutamyl transferase (GGT), and total bilirubin (TB). The optimal combination of laboratory values was determined by an algorithm developed in the Python programming language.

      Results

      Of 640 women who met the inclusion criteria, 22% (n = 142) were diagnosed with ICP (serum BA>10 μmol/L). A combined laboratory score of: (TB>11 μmol/L) or (ALK>255 U/L) or (GGT>32 U/L) or (AST>31 U/L), had a sensitivity of 94%, negative predictive value (NPV) of 97%, specificity of 50%, positive predictive value of 35%, and a negative likelihood ratio of 0.11 for the diagnosis of ICP. The AUC of the laboratory model alone was 0.72 (95% CI: 0.69–0.75). The addition of history of ICP to the suggested laboratory score resulted in a sensitivity of 97%, NPV of 98% and a negative likelihood ratio of 0.06. The AUC of the final model was 0.76 (95% CI: 0.72–0.79).

      Conclusions

      A combined laboratory score incorporating AST, GGT, ALK and TB was shown to reliably exclude the diagnosis of ICP. This may be particularly useful in settings with limited access to BA levels testing.

      Graphical abstract

      Keywords

      Abbreviations:

      ALK (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), GGT (gamma glutamyl transferase), ICP (intrahepatic cholestasis of pregnancy), TB (total bilirubin)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Allen A.M.
        • Kim W.R.
        • Larson JJ.
        The epidemiology of liver diseases unique to pregnancy in a US community: a population-based study.
        Clin Gastroenterol Hepatol. 2016; 14 (e1, 2): 287-294
        • Lee R.H.
        • Goodwin T.M.
        • Greenspoon J.
        • Incerpi M.
        The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population.
        J Perinatol. 2006; 26: 527-532
        • Williamson C.
        • Geenes V.
        Intrahepatic cholestasis of pregnancy.
        Obstet Gynecol. 2014; 124: 120-133
        • Sinakos E.
        • Lindor KD.
        Bile acid profiles in intrahepatic cholestasis of pregnancy: is this the solution to the enigma of intrahepatic cholestasis of pregnancy?.
        Am J Gastroenterol. 2010; 105: 596-598
        • Wood A.M.
        • Livingston E.G.
        • Hughes B.L.
        • Kuller JA.
        Intrahepatic cholestasis of pregnancy: a review of diagnosis and management.
        Obstet Gynecol Surv. 2018; 73: 103-109
        • Di Mascio D.
        • Quist-Nelson J.
        • Riegel M.
        • George B.
        • Saccone G.
        • Brun R.
        • et al.
        Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review.
        J Matern Fetal Neonatal Med. 2019; : 1-9
        • Ovadia C.
        • Seed P.T.
        • Sklavounos A.
        • Geenes V.
        • Di Ilio C.
        • Chambers J.
        • et al.
        Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.
        Lancet. 2019; 393: 899-909
        • Glantz A.
        • Marschall H.U.
        • Mattsson LÅ.
        Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates.
        Hepatology. 2004; 40: 467-474
        • Geenes V.
        • Chappell L.C.
        • Seed P.T.
        • Steer P.J.
        • Knight M.
        • Williamson C.
        Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study.
        Hepatology. 2014; 59: 1482-1491
        • Cui D.
        • Zhong Y.
        • Zhang L.
        • Du H.
        Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: a meta-analysis.
        J Obstet Gynaecol Res. 2017; 43: 1411-1420
      1. Society for maternal-fetal medicine (SMFM) consult series #53: intrahepatic cholestasis of pregnancy.
        Am J Obstet Gynecol. 2021; 224: B2-B9
        • Donet A.
        • Girault A.
        • Pinton A.
        • Lepercq J.
        Intrahepatic cholestasis of pregnancy: is a screening for differential diagnoses necessary?.
        J Gynecol Obstet Hum Reprod. 2020; 101907
        • Jacquemin E.
        • Cresteil D.
        • Manouvrier S.
        • Boute O.
        • Hadchouel M.
        Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy.
        Lancet. 1999; 353: 210-211
        • Dixon P.H.
        • Weerasekera N.
        • Linton K.J.
        • Donaldson O.
        • Chambers J.
        • Egginton E.
        • et al.
        Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking.
        Hum Mol Genet. 2000; 9: 1209-1217
        • Gonzalez M.C.
        • Reyes H.
        • Arrese M.
        • Figueroa D.
        • Lorca B.
        • Andresen M.
        • et al.
        Intrahepatic cholestasis of pregnancy in twin pregnancies.
        J Hepatol. 1989; 9: 84-90
        • Williamson C.
        • Hems L.M.
        • Goulis D.G.
        • Walker I.
        • Chambers J.
        • Donaldson O.
        • et al.
        Clinical outcome in a series of cases of obstetric 376 cholestasis identified via a patient support group.
        BJOG. 2004; 111: 676-681