eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 15
Clinical research

Evaluation of FGF-19 and β-klotho as biomarkers in patients with intrahepatic cholestasis of pregnancy

Ahter Tanay Tayyar, Ahmet Tayyar, Sukran Kozali, Resul Karakus, Nadiye Koroglu, Ilkbal Temel Yuksel, Gonca Yetkin Yildirim, Ismail Dag, Mustafa Eroglu

Arch Med Sci 2019; 15, 1: 113–119
Online publish date: 2018/01/10
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Fibroblast growth factor-19 (FGF-19) and its co-receptor, beta-klotho, regulate bile acid synthesis in the liver as an enterohepatic feedback mechanism. In this study, our aim was to investigate the circulating FGF-19 and β-klotho levels in intrahepatic cholestasis of pregnancy (ICP) cases.

Material and methods
A cross-sectional study including 40 women whose pregnancies were complicated with ICP were recruited for the study group. Forty randomly selected healthy pregnant women comprised the control group. The patient characteristics, including maternal age, gravidity, parity, gestational age at the time of diagnosis, body mass index (BMI), and obstetric history, were recorded. The serum FGF-19 and β-klotho concentrations were measured using an enzyme-linked immunosorbent assay.

Maternal age, gravidity, parity, body mass index at assessment, and gestational age at blood sampling were similar between the two groups (p > 0.05). Moreover, there were no significant differences in the FGF-19 and β-klotho concentrations between the two groups (p = 0.341 and p = 0.086, respectively). A positive correlation was detected between the β-klotho and FGF-19 levels, as well as between the FGF-19 level and BMI (r = 0.368, p = 0.020 and r = 0.389, p = 0.013, respectively).

The serum FGF-19 and β-klotho concentrations did not differ between the pregnancies with ICP and the healthy controls. However, in some cases, abnormalities in the FGF-19, β-klotho, and FGFR4 signaling system may play roles in the pathogenesis of ICP.


fibroblast growth factor-19, β-klotho, intrahepatic cholestasis of pregnancy, pathogenesis, CYP7A1

Fagan EA. Intrahepatic cholestasis of pregnancy. Clin Liver Dis 1999; 3: 603-32.
Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. Liver disease in pregnancy. Lancet 2010; 375: 594-605.
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.
Geenes V, Chappell LC, Seed PT, Steer PJ, 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: 1482-91.
Tayyar AT, Tayyar A, Atakul T, et al. Could first- and second-trimester biochemical markers for Down syndrome have a role in predicting intrahepatic cholestasis of pregnancy? Arch Med Sci 2017; doi: 10.5114/aoms.2017.69865.
Gutaj P, Wender-Ożegowska E, Brązert J. Maternal lipids associated with large-for-gestational-age birth weight in women with type 1 diabetes: results from a prospective single-center study. Arch Med Sci 2016; 13: 753-9.
Kulhan M, Kulhan NG, Nayki U, Nayki C, Ata N. Intrahepatic cholestasis of pregnancy and fetal outcomes. Mini review. Arch Med Sci Civil Dis 2017; 2: 85-6.
Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med 2008; 10: e9.
Koroglu N, Tayyar A, Tola EN, et al. Increased levels of the novel hepatokine Fetuin B in patients with intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med 2017; doi: 10.1080/14767058.2017.1413546.
Beuers U, Trauner M, Jansen P, Poupon R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol 2015; 62: S25-37.
Holt JA, Luo G, Billin AN, et al. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev 2003; 17: 1581-91.
Kuro-o M. Endocrine FGFs and Klothos: emerging concepts. Trends Endocrinol Metab 2008; 19: 239-45.
Inagaki T, Choi M, Moschetta A, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2005; 2: 217-25.
Wu X, Ge H, Gupte J, et al. Co-receptor requirements for fibroblast growth factor-19 signaling. J Biol Chem 2007; 282: 29069-72.
Lin BC, Wang M, Blackmore C, Desnoyers LR. Liver-specific activities of FGF19 require Klotho beta. J Biol Chem 2007; 282: 27277-84.
Ornitz DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol 2015; 4: 215-66.
Ito S, Fujimori T, Furuya A, Satoh J, Nabeshima Y, Nabeshima Y. Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho. J Clin Invest 2005; 115: 2202-8.
Ahmed KT, Almashhrawi AA, Rahman RN, Hammoud GM, Ibdah JA. Liver diseases in pregnancy: diseases unique to pregnancy. World J Gastroenterol 2013; 19: 7639-46.
Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol 2014; 124: 120-33.
Hepburn IS, Schade RR. Pregnancy-associated liver disorders. Dig Dis Sci 2008; 53: 2334-58.
Tayyar A, Temel Yuksel I, Koroglu N, et al. Maternal copeptin levels in intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med 2017. doi: 10.1080/14767058.2017.1335708.
Van Mil SW, Milona A, Dixon PH, et al. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. Gastroenterology 2007; 133: 507-16.
Bacq Y, Sapey T, Brechot MC, Pierre F, Fignon A, Dubois F. Intrahepatic cholestasis of pregnancy: a French prospective study. Hepatology 1997; 26: 358-64.
Schaap FG, van der Gaag NA, Gouma DJ, Jansen PL. High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis. Hepatology 2009; 49: 1228-35.
Angelin B, Larsson TE, Rudling M. Circulating fibroblast growth factors as metabolic regulators: a critical appraisal. Cell Metab 2012; 16: 693-705.
Kliewer SA, Mangelsdorf DJ. Bile acids as hormones: the FXR-FGF15/19 pathway. Dig Dis 2015; 33: 327-31.
Yu C, Wang F, Kan M, et al. Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J Biol Chem 2000; 275: 15482-9.
Dixon PH, Wadsworth CA, Chambers J, 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.
Wunsch E, Milkiewicz M, Wasik U, et al. Expression of hepatic fibroblast growth factor 19 is enhanced in primary biliary cirrhosis and correlates with severity of the disease. Sci Rep 2015; 5: 13462.
Li Z, Lin B, Lin G, et al. Circulating FGF19 closely correlates with bile acid synthesis and cholestasis in patients with primary biliary cirrhosis. PLoS One 2017; 12: e0178580.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe