Jurate K, Rimantas Z, Jolanta S, Vladas G, Limas K

Language: English
References: 26
Page: 569-573
PDF size: 133.75 Kb.

ABSTRACT

Background and aim. Intrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Material and methods. Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. Results. ICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P ‹ 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P ‹ 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/ L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. Conclusion. The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.

REFERENCES

1. Riely CA, Bacq Y. Intrahepatic cholestasis of pregnancy. Clin Liver Dis 2004; 8: 167-76.

2. Beuers U, Kremer AE, Bolier R, Elferink RP. Pruritus in cholestasis: Facts and fiction. Hepatology 2014; 60: 399- 407.

3. Kondrackiene J, Kupcinskas L. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems. World J Gastroenterol 2008; 14: 5781-8.

4. Dixon PH, Wadsworth CA, Chambers J, Donnelly J, Cooley S, Buckley R, Mannino R, et al. A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy. Am J Gastroenterol 2014; 109: 76-84.

5. Sookoian S, Castaño G, Burgueño A, Gianotti TF, Pirola CJ. Association of the multidrug-resistance-associated protein gene (ABCC2) variants with intrahepatic cholestasis of pregnancy. J Hepatol 2008; 48: 125-32.

6. Germain AM, Kato S, Carvajal JA, Valenzuela GJ, Valdes GL, Glasinovic JC. Bile acids increase response and expression of human myometrial oxytocin receptor. Am J Obstet Gynecol 2003; 189: 577-82.

7. Glantz A, Marschall H-U, Mattsson L-A. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology 2004; 4: 467- 74.

8. Geenes V, Chappell LC, Seed PT, Steer PJ, Williamson C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population- based case-control study. Hepatology 2014; 59: 1482- 91.

9. Rook M, Vargas J, Caughey A, Bacchetti P, Rosenthal P, Bull L. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort. PLoS One 2012; 7: e 28343.

10. Oztekin D, Aydal I, Oztekin O, Okcu S, Borekci R, Tinar S. Predicting fetal asphyxia in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 2009; 280: 975-9.

11. Kondrackiene J, Beuers U, Zalinkevicius R, Tauschel HD, Gintautas V, Kupcinskas L. Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy. World J Gastroenterol 2007; 13: 6226-30.

12. Silver RM, Parker CB, Goldenberg R, Reddy UM, Dudley DJ, Saade GR, Hogue CJ, et al. Bile acids in a multicenter, population- based case-control study of stillbirth. Am J Obstet Gynecol 2014; 210: 460.e1-9.

13. Chen J, Deng W, Wang J, Shao Y, Ou M, Ding M. Primary bile acids as potential biomarkers for the clinical grading of intrahepatic cholestasis of pregnancy. Int J Gynaecol Obstet 2013; 122: 5-8.

14. Huang WM, Gowda M, Donnelly JG. Bile acid ratio in diagnosis of intrahepatic cholestasis of pregnancy. Am J Perinatol 2009; 26: 291-4.

15. Geenes V, Catherine Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009; 15: 2049-66.

16. Kariv R, Leshno M, Beth-Or A, Strul H, Blendis L, Kokia E, Noff D, et al. Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study. Liver Int 2006; 26: 445-50.

17. Kremer AE, Martens JJ, Kulik W, Ruëff F, Kuiper EM, van Buuren HR, van Erpecum KJ, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology 2010; 139: 1008-18.

18. Kremer AE, Bolier R, Dixon PH, Geenes V, Chambers J, Tolenaars D, Ris-Stalpers C, et al. Autotaxin Activity has a high Accuracy to diagnose Intrahepatic Cholestasis of Pregnancy. J Hepatol 2015; 62: 897-904.

19. Kondrackiene J, Beuers U, Kupcinskas L. Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy. Gastroenterology 2005; 129: 894-901.

20. Stellaard F, Sackmann M, Sauerbruch T, Paumgartner G. Simultaneous determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates in human serum using 13C-labeled bile acids. J Lipid Res 1984; 25: 1313-9.

21. Sentilhes L, Verspyck E, Pia P, Marpeau L. Fetal death in a patient with intrahepatic cholestasis of pregnancy. Obstet Gynecol 2006; 107: 458.

22. Castano G, Lucangioli S, Sookoian S, Mesquida M, Lemberg A, Di Scala M, Franchi P, et al. Bile acid profiles by capillary electrophoresis in intrahepatic cholestasis of pregnancy. Clin Sci (Lond) 2006; 110: 459-65.

23. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: 1-10.

24. Girling JC, Dow E, Smith JH. Liver function tests in pre-eclampsia: importance of comparison with a reference range derived for normal pregnancy. Br J Obstet Gynaecol 1997; 104: 246-50.

25. Ropponen A, Sund R, Riikonen S, Ylikorkala O, Aittomaki K. Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population-based study. Hepatology 2006; 43: 723-8.

26. Marschall HU, Wikström Shemer E, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology 2013; 58: 1385-91.