Intrahepatic Cholestasis Of Pregnancy And Its Management

Yıl 2015, Cilt: 12 Sayı: 6, 217 - 220, 01.12.2015

Ali Özgür Ersoy , Dilek Uygur

Öz

Intrahepatic cholestasis of pregnancy ICP is the most frequent liver disease in pregnancy and is specific to pregnancy period. Genetic, hormonal, environmental factors have been accused in its pathogenesis. Pruritus is the first and the most frequent symptom of the disease. Progressive increase in serum transaminase and bile acid levels are frequent laboratorial findings. The maternal complications of ICP are rare, but include gallstones, cholecystitis, pancreatitis and liver cirrhosis. ICP also increases the risk of fetal and neonatal complications, such as perinatal mortality, stillbirth, low birth weight, fetal distress in labor and meconium aspiration, preterm labor and birth, fetal and neonatal arrhythmia. ICP may recur in subsequent pregnancies for more than 50 per cent. Ursodeoxycholic acid is the most effective therapeutic option to provide the best symptomatic and laboratorial results, but there’s not enough data to assure satisfying neonatal outcomes. Generally, induction of labor in the 37th weeks of gestation was showed to lower perinatal mortality in many studies. Studies to find out the genetic basis of the disease comprehensively are still carried on. In the future, it’s expected that partially or complete alleviation of the disease may be provided at the hands of decryption and treatment of situations which cause genetic proneness, while it’s considered as a highly repetitive disease.

Anahtar Kelimeler

Obstetric cholestasis, pathogenesis, management, timing for delivery

Gebeliğin İntrahepatik Kolestazı ve Yönetimi

Öz

Gebeliğin intrahepatik kolestazı, gebeliğe özgü olup, gebelikte en sık rastlanan karaciğer hastalığıdır. Patogenezinde genetik, hormonsal ve çevresel faktörler suçlanmıştır. Kaşıntı, ilk ve en sık gözlenen şikayettir. Karaciğer fonksiyonlarını gösteren serum transaminaz ve safra asitleri düzeylerinin ilerleyici artışı sık görülen laboratuvar bulgularıdır. Hastalığın maternal komplikasyonları safra taşları, kolesistit, pankreatit ve siroz gibi hastalıklar olup, nadir gelişir. Fetal ve neonatal açıdan da prematürite, düşük doğum ağırlığı, perinatal ölüm, mekonyum aspirasyon sendromu, eylemde fetal distres, fetal ve neonatal aritmi görülebilmektedir. Sonraki gebeliklerde %50 üzeri bir oranda tekrarlama olasılığı vadır. Tedavide en etkili semptomatik ve laboratuvar iyileşmesini sağlayan ilaç ursodeoksikolik asit olup, neonatal sonuçları iyileştirdiğine dair yeterli kanıt yoktur. Genelde, 37 gebelik haftasında indüklenen doğumun perinatal ölümü azalttığına dair çok sayıda veri vardır. Hastalığın genetik temellerine dair çalışmalar halen sürmektedir. Hastalığın büyük ölçüde tekrarlayıcı olabildiği düşünüldüğünde, gelecekte, genetik yatkınlık yaratan durumların tespit ve tedavisiyle, , daha hafif geçirilmesi veya tam iyileşme sağlanabilmesi beklenmektedir.

Anahtar Kelimeler

Gebelik kolestazı, patogenez, yönetim, doğum zamanlaması

Kaynakça

• Heinonen S, Kirkinen P. Pregnancy outcome with intrahepatic cholesta- sis. Obstet Gynecol 1999;94:189-93.
• Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of preg- nancy: Relationships between bile acid levels and fetal complication ra- tes. Hepatology 2004;40:467-74.
• Reyes H, Radrigan ME, Gonzalez MC, et al. Steatorrhea in patients with intrahepatic cholestasis of pregnancy. Gastroenterology 1987;93:584- 90.
• Vallejo M, Briz O, Serrano MA, Monte MJ, Marin JJ. Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. Journal of Hepatology 2006;44:1150–7
• Huang L, Zhao A, Lew JL, et al. Farnesoid X Receptor activates transcrip- tion of the phospholipid pump MDR3. J Biol Chem 2003;278:51085-90.
• Milkiewicz P, Gallagher R, Chambers J, Eggington E, Weaver J, Elias E. Obstetric cholestasis with elevated gamma glutamyl transpeptida- se: Incidence, presentation and treatment. J Gastroenterol Hepatol 2003;18:1283.
• Lammert F, Marschall HU, Glantz A, Matern S. “Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management”. J Hepatol 2000;33: 1012–21.
• Meng LJ, Reyes H, Axelson M, Palma J, Hernandez I, Ribalta J, Sjovall J. Progesterone metabolites and bile acids in serum of patients with int- rahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid the- rapy. Hepatology 1997;26:1573-1579.
• Reyes H. Review: Intrahepatic cholestasis. A puzzling disorder of preg- nancy. Journal of Gastroenterology and Hepatology 1997;12:211-216
• Kauppila A, Korpela H, Makila UM, et al. Low serum selenium concent- ration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br Med J Clin Res Ed 1987;294:150-2.
• Agostini A, Gerli GC, Beretta L, et al. Erythrocyte antioxidant enzymes and selenium serumn levels in an Andean population. Clin Chim Acta 1983;133:153-7.
• Williamson C, Hems L, Goulis D, et al. Clinical outcome in a series of ca- ses of obstetric cholestasis identified via a patient support group. BJOG 2004;111:676-81
• Alsulyman OM, Ouzounian JG, Ames-Castro M, et al. Intrahepatic cho- lestasis of pregnancy: Perinatal outcome associated with expectant ma- nagement. Am J Obstet Gynecol 1996;175:957-60.
• 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; 18:577-582.
• Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, Moshkov AV, Xie Q, Keitel V, Nikolaev VO, Williamson C, Gorelik J. Bile acid-induced arrhyth- mia is mediated by muscarinic M2 receptors in neonatal rat cardiomyo- cytes. PLoS One. 2010;5:9689.
• Floreani A, Carderi I, Paternoster D, Soardo G, Azzaroli F, Esposito W, Montagnani M, Marchesoni D, Variola A, Rosa Rizzotto E, Braghin C, Mazzella G. Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy. Dig Liver Dis 2008; 40: 366-370
• 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;7:28343.
• Brouwers L, Koster MP, Page-Christiaens GC, Kemperman H, Boon J, Evers IM, Bogte A, Oudijk MA. Intrahepatic Cholestasis Of Pregnancy: Maternal and Fetal Outcomes Associated With Elevated Bile Acid Levels. Am J Obstet Gynecol. 2014 ; 18: 726-731.
• Yu L, Ding Y, Huang T, Huang X. Effect of bile Acid on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Int J Endocrinol. 2014;2014:308274.
• Zhang LJ, Xiang H, Ding YL. Influence of total bile acid in maternal serum and cord blood on neonatal cardiac function from intrahepatic cholesta- sis of pregnancyZhonghua Fu Chan Ke Za Zhi. 2009;44:188-90.
• Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver di- sease: mechanisms of action and therapeutic use revisited. Hepatology 2002;36:525–531 .
• European Association for the Study of the Liver. EASL Clinical Practi- ce Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237–267.
• Mazzella G, Rizzo N, Azzaroli F, Simoni P, Bovicelli L, Miracolo A, Simo- nazzi G, Colecchia A, Nigro G, Mwangemi C, Festi D, Roda E. Ursode- oxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers. Hepatology 2001; 33: 504-508.
• Diken Z, Usta IM, Nassar AH. A clinical approach to intrahepatic choles- tasis of pregnancy. Am J Perinatol. 2014;31:1-8.
• Nicastri PL, Diaferia A,Tartagni M, Loizzi P, Fanelli M. Arandomised pla- cebo-controlled trial of ursodeoxycholic acid and S-adenosyl methionine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol 1998;105:1205–1207.
• Binder T, Salaj P, Zima T, Vítek L. Randomized prospective compara- tive study of ursodeoxycholic acid and S-adenosyl L-methionine in the treatment of intrahepatic cholestasis of pregnancy. J Perinat Med 2006;34:383–391.
• Pathak B, Sheibani L, Lee RH. Cholestasis of pregnancy. Obstet Gynecol Clin North Am. 2010;37:269-82.
• Fisk NM, Storey GN. Fetal outcome in obstetric cholestasis. Br J Obstet Gynaecol. 1988;95:1137-43.
• Royal College of Obstetricians and Gynaecologists. Obstetric cholesta- sis: Green-top Guideline no. 43. London: RCOG; 2011.
• American College of Obstetricians and Gynecologists. ACOG committee opinion no. 561: Nonmedically indicated early-term deliveries. Obstet Gynecol. 2013;121:911-5.
• Lee RH, Kwok KM, Ingles S, Wilson ML, Mullin P, Incerpi M, Pathak B, Goodwin TM. Pregnancy outcomes during an era of aggressive ma- nagement for intrahepatic cholestasis of pregnancy. Am J Perinatol. 2008;25:341-5.
• Kenyon AP, Piercy CN, Girling J, Williamson C, Tribe RM, Shennan AH. Obstetric cholestasis, outcome with active management: a series of 70 cases. BJOG 2002;109:282-8.
• Silver RM, Parker CB, Goldenberg R, Reddy UM, Dudley DJ, Saade GR, Hogue CJ, Coustan D, Varner MW, Koch MA, Conway D, Bukowski R, Pinar H, Stoll B, Moore J, Willinger M. Bile acids in a multicenter, popu- lation-based case-control study of stillbirth. Am J Obstet Gynecol. 2014 ;210:460;1-9.
• Henderson CE, Shah RR, Gottimukkala S, Ferreira KK, Hamaoui A, Mer- cado R. Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2014 ;211:189-96.
• Olsson R, Tysk C, Aldenborg F, Holm B. Prolonged postpartum course of intrahepatic cholestasis of pregnancy. Gastroenterology 1993;105:267– 271.
• Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15:2049–2066.