Merve ÖZTÜRK AĞAOĞLU, Zahid AĞAOĞLU, Şevki ÇELEN

İntrahepatik Gebelik Kolestazında Plazma Lipid Düzeylerinin Değerlendirilmesi

Amaç: Çalışmamızın amacı, intrahepatik gebelik kolestazı tanılı gebelerde total kolesterol, trigliserid, LDL, VLDL, HDL düzeylerini araştırmak ve hastalık şiddeti ile ilişkisini incelemektir. Gereç ve Yöntem: İntrahepatik gebelik kolestazı tanılı 40 ve benzer yaş grubunda 40 kontrol olmak üzere toplam 80 gebe prospektif olarak çalışmaya dahil edildi. Vaka ve kontrol grubu arasında lipid parametreleri karşılaştırıldı ve hastalık şiddeti ile ilişkisi analiz edildi. Doğum ağırlığı, doğumdaki gebelik haftası ve yenidoğan sonuçları incelendi. Bulgular: İntrahepatik gebelik kolestazı tanılı grupta sağlıklı gebelere göre LDL, VLDL düzeyleri anlamlı olarak daha yüksek ve HDL düzeyleri daha düşük saptandı (p<0,05). Total kolesterol ve trigliserid seviyeleri iki grupta benzerdi. Gebelik kolestazı grubunda doğum haftası, doğum kilosu ve 1-5.dakika Apgar skorları daha düşük, yenidoğan yoğun bakıma yatış ve primer sezaryen oranları daha yüksekti (p<0,05). Korelasyon analizinde, serum LDL ile safra asiti seviyeleri arasında pozitif yönde korelasyon saptandı (r=0,349, p=0,027). LDL düzeyi, şiddetli hastalık grubunda hafif hastalık grubuyla karşılaştırıldığında anlamlı olarak yüksekti (p=0,009). Sonuç: İntrahepatik gebelik kolestazında lipid homeostazında önemli değişiklikler meydana gelmektedir. LDL ve VLDL yüksekliği gibi anormal lipid düzeyleri gebelik kolestazı patogenezinde rol oynayabilir ve özellikle yüksek LDL kolesterol düzeyi kolestaz şiddetinin tahminine katkıda bulunabilir.

Anahtar Kelimeler:

Gebeliğin intrahepatik kolestazı, kolesterol, safra asitleri, triglseridler

Evaluation of Plasma Lipid Levels in Intrahepatic Cholestasis of Pregnancy

Objective: To investigate the total cholesterol, triglyceride, LDL, VLDL, and HDL levels of pregnant women diagnosed with intrahepatic cholestasis of pregnancy and to examine the association with disease severity. Material and Method: A total of 80 pregnant women, 40 of whom were diagnosed with intrahepatic cholestasis of pregnancy, and 40 age-matched controls, were prospectively enrolled in this study. Lipid levels were compared among the case and controls, and their association with disease severity was analyzed. Birth weight, birth week, and neonatal outcomes were studied. Results: LDL and VLDL were significantly higher, and HDL levels were lower in the intrahepatic cholestasis of the pregnancy group than in the healthy pregnancies (p<0.05). Total cholesterol and triglyceride levels did not differ among the two groups. Birth weight, birth week, and 1-5-minute Apgar scores were lower, and the neonatal intensive care unit admission and the rate of primary cesarean section were higher in the group with intrahepatic cholestasis in pregnancy (p<0.05). In correlation analysis, a positive correlation was found between serum LDL and bile acids levels (r=0.349, p=0.027). LDL levels were significantly higher in severe disease than in mild disease (p=0.009) Conclusion: There are significant changes in lipid homeostasis in intrahepatic cholestasis of pregnancy. Abnormal lipid levels, such as high LDL and VLDL levels, could have a role in the pathogenesis, and in particular high LDL levels may contribute to the prediction of disease severity.

Keywords:

Bile acids, cholesterol, intrahepatic cholestasis of pregnancy, triglycerides,

PDF

___

Girling J, Knight CL, Chappell L, Gynaecologists RCoOa. Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022. BJOG. 2022;129(13):e95-e114.
Yamamoto Y, Moore R, Hess HA, Guo GL, Gonzalez FJ, Korach KS, et al. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J Biol Chem 2006;281(24):16625-16631.
Rathi U, Bapat M, Rathi P, Abraham P. Effect of liver disease on maternal and fetal outcome--a prospective study. Indian J Gastroenterol. 2007;26(2):59-63.
Reyes H, Simon FR. Intrahepatic cholestasis of pregnancy: an estrogen-related disease. Semin Liver Dis 1993;13(3):289-301.
Dalén E, Westerholm B. Occurrence of hepatic impairment in women jaundiced by oral contraceptives and in their mothers and sisters. Acta Med Scand 1974;195(6):459-463.
Johnson P. Studies in cholestasis of pregnancy with special reference to lipids and lipoproteins. Acta Obstet Gynecol Scand Suppl 1973;27:1-80.
Reyes H. The spectrum of liver and gastrointestinal disease seen in cholestasis of pregnancy. Gastroenterol Clin North Am. 1992;21(4):905-21.
Nikkilä K, Riikonen S, Lindfors M, Miettinen TA. Serum squalene and noncholesterol sterols before and after delivery in normal and cholestatic pregnancy. J Lipid Res 1996;37(12):2687-2695.
Wojcicka J, Sienko J, Smolarczyk R, Romejko E, Grymowicz M, Czajkowski K. Alpha-hydroxybutyrate dehydrogenase activity in intrahepatic cholestasis of pregnancy. Int J Gynaecol Obstet 2005;89(3):247-250.
Schachter D. Fluidity and function of hepatocyte plasma membranes. Hepatology 1984;4(1):140-151.
Vore M. Estrogen cholestasis. Membranes, metabolites, or receptors? Gastroenterology 1987;93(3):643-649.
Sepúlveda WH, González C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol 1991;42(3):211-215.
Monte MJ, Morales AI, Arevalo M, Alvaro I, Macias RI, Marin JJ. Reversible impairment of neonatal hepatobiliary function by maternal cholestasis. Hepatology. 1996;23(5):1208-1217.
Johnson P, Samsioe G, Gustafson A. Studies in cholestasis of pregnancy. I. Clinical aspects and liver function tests. Acta Obstet Gynecol Scand 1975;54(1):77-84.
Dann AT, Kenyon AP, Wierzbicki AS, Seed PT, Shennan AH, Tribe RM. Plasma lipid profiles of women with intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2006;107(1):106-114.
Svanborg A, Vikrot O. Plasma lipids in recurrent jaundice of pregnancy. Acta Med Scand. 1967;181(1):83-7.
de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab 2013;17(5):657-669.
Fiorucci S, Mencarelli A, Palladino G, Cipriani S. Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol Sci 2009;30(11):570-580.
Chiang JYL, Ferrell JM. Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. Am J Physiol Gastrointest Liver Physiol 2020;318(3):G554-G573.
Keitel V, Dröge C, Häussinger D. Targeting FXR in Cholestasis. Handb Exp Pharmacol 2019;256:299-324.
Abu-Hayyeh S, Papacleovoulou G, Lövgren-Sandblom A, Tahir M, Oduwole O, Jamaludin NA, et al. Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype. Hepatology 2013;57(2):716-726.
Zhan Q, Qi X, Weng R, Xi F, Chen Y, Wang Y, et al. Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy. Front Cell Infect Microbiol. 2021;11:635680.
National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89(3):1333-1445.
Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15(17):2049-2066.
Lammert F, Marschall HU, Glantz A, Matern S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 2000;33(6):1012-1021.
Ovadia C, Seed PT, 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(10174):899-909.
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(4):1482-1491.
Blackwell SC, Wolfe HM, Redman ME, Hassan SS, Berry SM, Treadwell MC, et al. Relationship between meconium staining and amniotic fluid volume in term pregnancies. Fetal Diagn Ther 2002;17(2):78-82.