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acog intrahepatic cholestasis of pregnancy

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug ReferenceDisclosure: Received salary from Medscape for employment. The condition triggers intense itching, but without a rash. 2005 Jun. The most specific and sensitive marker of ICP is total serum bile acid (BA) levels greater than 10 micromol/L. Rioseco AJ, Ivankovic MB, Manzur A, Hamed F, Kato SR, Parer JT. Mabie WC, 9(1):84-90. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Jaundice may occur in 17-75% of cases of intrahepatic cholestasis of pregnancy (ICP) but typically develops 1-4 weeks after the onset of pruritus. Want to use this article elsewhere? [Medline]. It most commonly appears two to four weeks after the onset of itching. Intrahepatic cholestasis has an adverse effect on fetal development, and affected pregnancies merit closer surveillance. 2006 Jun 1. Intrahepatic cholestasis of pregnancy: an estrogen-related disease. Whitley RJ. [Medline]. Newman JS, 17. Griffin PH. 1996 Feb. 52(2):133-40. Liver Disease in Pregnancy. The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. Sadler LC, Lane M, North R. Severe fetal intracranial haemorrhage during treatment with cholestyramine for intrahepatic cholestasis of pregnancy. This case study presents the epidemiology, diagnosis, and management of intrahepatic cholestasis of pregnancy, a liver disorder resulting in impaired bile flow and pruritis. Barton JR, [Medline]. 2011 Feb. 15(1):199-208. [48]. Malangoni MA. Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. Prevalence of intrahepatic cholestasis of pregnancy in Chile. Intrahepatic cholestasis of pregnancy: an estrogen-related disease. 13(6):1084-9. Am J Obstet Gynecol. [Medline]. Mabie WC, Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. 1992;14:961–5. Nordenfelt E. According to Obstetrician / Gynecologists, 2001 Pata O, Vardareli E, Ozcan A, Serteser M, Unsal I, Saruç M. Intrahepatic cholestasis of pregnancy: correlation of preterm delivery with bile acids. (%) . Hepatic emergencies in pregnancy. 1992;15:1043–7. MR demonstration of reversible periportal abnormal intensity in eclampsia. Hepatology. This content is owned by the AAFP. Turk J Gastroenterol. Sims HF, [Medline]. Lee RH, Goodwin TM, Greenspoon J, Incerpi M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. Intrahepatic cholestasis is reported infrequently in most countries except for China, Bolivia, and Scandinavia. [Medline]. BJOG. Rinaldo P, Intrahepatic cholestasis of pregnancy (ICP) is a potentially serious liver disorder that can develop in pregnancy. [48] In addition to the elevation in serum BA levels, the cholic acid level is significantly increased and the chenodeoxycholic acid level is mildly increased, leading to elevation in the cholic/chenodeoxycholic acid level ratio. Edwards VM, Kawakita T, Parikh LI, Ramsey PS, Huang CC, Zeymo A, Fernandez M, et al. The nonstress test: an evaluation of 1,000 patients. 62 (4):897-904. Gastroenterol Clin North Am. Gonzalez MC, Reyes H, Arrese M, Figueroa D, Lorca B, Andresen M, et al. Smith SK, Malangoni MA. Morrison JC, Favre N, Abergel A, Blanc P, Sapin V, Roszyk L, Gallot D. Unusual presentation of severe intrahepatic cholestasis of pregnancy leading to fetal death. ICP should be suspected in cases of pruritis lacking a rash, though it should be noted that a rash may develop secondarily as a result of intense scratching. Hämäläinen ST, Turunen K, Mattila KJ, Sumanen M. Intrahepatic cholestasis of pregnancy and associated causes of death: a cohort study with follow-up of 27-46 years. Kremer AE, Bolier R, Dixon PH, Geenes V, Chambers J, Tolenaars D, et al. et al. [Medline]. Mohamud O, Fallon WF Jr, Cairns SR, Mosley JW. In cases of acute hepatitis B virus infection complicating pregnancy, the prevalence of neonatal infection depends on the time during gestation that maternal infection occurs.12 Neonatal hepatitis B virus infection is rare if maternal infection takes place in the first trimester. Gastroenterol Clin North Am. Obstet Gynecol Clin North Am. Arch Gynecol Obstet. Chauhan SP, [Medline]. 1994;171:1154–8. Barton JR, All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Dig Dis. [Medline]. et al. Griffin PH. Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo gravidarum, is a medical condition in which cholestasis occurs during pregnancy.It typically presents with itching and can lead to complications for both mother and baby.. Pruritus (itching) is a common symptom of pregnancy, affecting around 23% of women. Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. 1991 Jun. The itching is typically severe and worst at night. 2010 Feb 13. Togashi K, Hepatitis in pregnancy. 26. 88(4):487-93. Manzur A, 2011. Vertical transmission of the virus has been reported to occur in two of three infants of mothers with acute hepatitis C virus infection, suggesting a higher risk of vertical transmission than occurs in patients with chronic infection, secondary to the high levels of hepatitis C virus RNA that occur in acute infection.14 Interferon therapy should not be administered during pregnancy because of its possible adverse effects on the fetus.15. 05 June 2017. Martinez E, Rodriguez N, Lisonim et al. Hansson BG, Palmer RM, ICP temporarily impairs (lowers) liver function in some pregnant women. Chari RS, [48] In addition to the elevation in serum BA levels, the cholic acid level is significantly increased and the chenodeoxycholic acid level is mildly increased, leading to elevation in the cholic/che… 1995;345:124–5. Manzur A, Millington DS, Am J Obstet Gynecol. [Medline]. 15(8):897-906. Rev Chil Obstet Ginecol. Harris RL, Hyams JS, Such defects in fatty acid oxidation are initially suggested by elevations in urinary organic acid levels and in plasma carnitine and acylcarnitine levels, detected after an overnight fast.32 Recurrent acute fatty liver of pregnancy has been reported in mothers expressing heterozygous long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.31,32,34. Shanklin DR. J Hepatol. Am J Obstet Gynecol. Obstet Gynecol. Van Thiel DH, Kaplan MM. [Medline]. The risk of recurrence of HELLP syndrome in subsequent pregnancies has been reported as 3.4 percent.24, Acute fatty liver of pregnancy most frequently complicates the third trimester and is commonly associated with preeclampsia (50 to 100 percent).2,3 Although rare (with an incidence of one in 13,000), acute fatty liver of pregnancy is a life-threatening condition, with an 18 percent maternal and a 23 percent fetal mortality rate.30. Immediate, unlimited access to all AFP content. [49, 50] The elevation of aminotransferases associated with ICP varies from a mild increase to a 10- to 25-fold increase. [Medline]. [Medline]. Gut. Riely CA, ACOG and SMFM have released guidance on the timing of medically indicated late-preterm and early-term deliveries, based on placental, fetal and maternal complications. Cholestasis of pregnancy is a common liver disease that causes severe itching late in pregnancy. 1994;18:143–5. Current pharmacotherapy for cholestatic liver disease. [Medline]. Iglesias J, Clin Infect Dis. Boyer TD. 2012 Jun 13. However, in pregnant patients with cholestatic liver disease, the pruritus can be severely disabling, and ursodeoxycholic acid therapy provides safe and effective relief. [15], BA levels have been suggested to be used for diagnosis and management of ICP but there is no uniform agreement on the criteria for diagnosing ICP. Symptoms associated with acute fatty liver of pregnancy include anorexia, nausea, emesis, abdominal pain, jaundice, headache and central nervous system disturbances.3,30 Hepatic histopathology reveals pericentral microvesicular fat with minimal inflammation or necrosis. 1993 Aug. 13(3):289-301. Proc Natl Acad Sci U S A. [Medline]. Duffy TP. Cotton PB. 1995;172(4 Pt 1):1107–25. Doppler umbilical artery velocimetry in pregnancies complicated by intrahepatic cholestasis. [Medline]. Hepatic disease in pregnancy. Recommended laboratory studies for the diagnosis of ICP include total serum bile acid levels, cholic acid, chenodeoxycholic acid (to evaluate the cholic/chenodeoxycholic acid ratio), total bilirubin, transaminases, GGT, PT, PTT, and INR. Hepatology. Laatikainen T. Effect of cholestyramine and phenobarbital on pruritus and serum bile acid levels in cholestasis of pregnancy. Am J Obstet Gynecol. et al. J Hepatol. et al. Obstet Gynecol. 1(6014):870-2. The clinical features are maternal pruritus in the absence of a rash and deranged liver function tests, including raised serum bile acids. https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMTU2MjI4OC13b3JrdXA=. Poupon R. Intrahepatic cholestasis of pregnancy: from bedside to bench to bedside. Martin JN Jr. 1994;96(1A):18S–22S. Shen Y, Zhou J, Zhang S, Wang XL, Jia YL, He S, et al. James DK. Acute fatty liver of pregnancy. Sharara AI, Am J Gastroenterol. Hansson BG, Jaundice may occur in 17-75% of cases of intrahepatic cholestasis of pregnancy (ICP) but typically develops 1-4 weeks after the onset of pruritus. Hepatic infarction is best detected by using computed tomographic scans or magnetic resonance imaging.2,36 Patients typically present with fever and marked elevations in transaminase levels. Sjogren MH. [Medline]. 2012 Aug 11. One group of investigators17 reported safely performing endoscopic retrograde cholangiopancreatography and endoscopic retrograde sphincterotomy without complications in five pregnant women (in the second and third trimesters) with choledocholithiasis using minimal fluoroscopy and lead aprons to shield the abdomen. Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder in the late second and early third trimester of pregnancy. These laboratory studies are used in conjunction with physical examination and symptoms to make a diagnosis of ICP. Roberts WE, Normally, bile acids flow from your liver to your gut to help you digest food. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. 1982 Dec. 14(3):153-62. Intrahepatic cholestasis complicates 0.01 to 0.02 percent of pregnancies in North America, 1 to 1.5 percent of pregnancies in Sweden and 5 to 21 percent of pregnancies in Chile.20 The disease is rare in black patients.20 A strong family history of cholestasis of pregnancy is typically described by the patient.20 Kindred studies reveal alterations in bromosulfophthalein clearance following estrogen treatment in both male and female relatives of women affected by intrahepatic cholestasis of pregnancy.19. Gastroenterol Clin North Am. 6. Ambros-Rudolph CM. Parer JT, Lees C, Contraception. 1985;313:367–70. / Journals 30. Fallon GL, ICP typically presents after 28 weeks of gestation with pruritus most commonly of the palms of the hands and soles of the feet, and sometimes intractable. Hepatobiliary diseases in women. Sharara AI. Multiple medications have been tried as treatments for cholestasis of pregnancy.19 Parenteral vitamin K (phytonadione; Aqua-Mephyton) supplementation is advocated in patients with prolonged cholestasis (secondary to malabsorption of this fat-soluble vitamin). Lee NM, Brady CW. [Medline]. It is also known as intrahepatic cholestasis of pregnancy (ICP) or obstetric cholestasis. Surg Gynecol Obstet. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. [Full Text]. Harris RL, Acute viral hepatitis is the most common cause of jaundice in pregnancy. Glorioso DV, CA Herrera, TA Manuck, GJ Stoddard, MW Varner, S Esplin, EA Clark, et al. 2006 Sep. 26(9):527-32. Diseases & Conditions, 2001 In surviving patients, liver function and histopathology are normal within six months of delivery.2,36 Intrahepatic hemorrhage has been reported to recur in a minority of subsequent pregnancies.35, An increased risk of fetal loss has been noted in pregnant patients with chronic liver disease.37 Therapy with penicillamine (Cuprimine), trientine (Syprine), prednisone or azathioprine (Imuran) can be safely continued during pregnancy in patients with Wilson's disease or autoimmune hepatitis.37 In patients with primary biliary cirrhosis, ursodeoxycholic acid therapy can be safely continued.37 In patients with chronic hepatitis B or C infection, interferon therapy should be discontinued during pregnancy, as its effects on the fetus are unknown.37, A marked reduction in fertility has been noted in cirrhotic patients.37 Cholestasis may worsen during pregnancy in patients with primary biliary cirrhosis. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Isse A, Millington DS, Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal MedicineDisclosure: Nothing to disclose. Hunt CM, 1987. Hepatology. Glorioso DV, This case study presents the epidemiology, diagnosis, and management of intrahepatic cholestasis of pregnancy, a liver disorder resulting in impaired bile flow and pruritis. Pregnancies complicated by liver disease and liver dysfunction. Get Permissions, Access the latest issue of American Family Physician. 375(9714):594-605. Therefore, an increasing number of patients with hepatitis C virus infection are requesting information about vertical transmission of the virus during pregnancy.13. Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and an elevation in serum bile acid concentrations, typically developing in the late second and/or third trimester and rapidly resolving after delivery. Ursodeoxycholic acid (Actigall), given at dosages of 15 mg per kg per day, has been the most successful therapy for cholestasis of pregnancy, as it ameliorates both the pruritus and liver function abnormalities and is well-tolerated by both mother and fetus.21 Ursodeoxycholic acid has been proved safe in trials of cholestatic liver disease in infants, children and adults. Sibai BM, (RUQ = right upper quadrant). McPeak C, [Medline]. Treatment of HELLP syndrome with nitric oxide donor [Letter]. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. Viral hepatitis, A through E, complicating pregnancy. Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. [Medline]. 32(4):542-9. 1990;171:1–4. New Insights on Intrahepatic Cholestasis of Pregnancy. Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. ... ABCB11, or NRH1HA encoding familial intrahepatic cholestasis 1 protein (FIC1), the bile salt export pump, or farnesoid X receptor (a regulator of bile acid synthesis and transport in … Barrett JM, Salyer SL, Boehm FH. Reprints are not available from the authors. Intrahepatic cholestasis of pregnancy: review of the literature. 1993;11:313–24. 2007 May 29. Thursby M, Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. 1994;170:890–5. Reyes H, Diagnosis of ICP may thus be made in the presence of pruritus without a rash in the absence of other liver disease in a gravid patient beyond 25 weeks’ gestation with the elevation of serum BA and/or aminotransferases levels. 1992 Jun. Curr Opin Obstet Gynecol. S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results. 2011 Mar. Sibai BM, Riely CA. James DK. 122(1):5-8. Am Fam Physician. 1999 Feb 15;59(4):829-836. Riely CA. 16. Stacey Ehrenberg-Buchner, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Society for Maternal-Fetal MedicineDisclosure: Nothing to disclose. Wang C, Chen X, Zhou SF, Li X. Efficacy of Ursodeoxycholic Acid in Treating Intrahepatic Cholestasis of Pregnancy: a Meta-Analysis. Reid R, Ivey KJ, Rencoret RH, Storey B. Fetal complications of obstetric cholestasis. Baillie J, Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. Relationship between nitric oxide synthesis and increase in systolic blood pressure in women with hypertension in pregnancy. The liver serves multiple functions: the biotransformation of insoluble compounds (e.g., drugs, toxins, bilirubin), the metabolism and excretion of cholesterol and bilirubin, the production of plasma proteins (e.g., albumin, coagulation factors, alpha- and beta-globulins, transferrin, haptoglobin), and the metabolism of amino acids, carbohydrates and lipids. Usefulness of fetal monitoring in intrahepatic cholestasis of pregnancy: a prospective study. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy. 1985;313:1327–30. The mechanical PR interval in fetuses of women with intrahepatic cholestasis of pregnancy. Dixon PH, Weerasekera N, Linton KJ, et al. 4(February 15, 1999) We will cover background, work-up, and management options for this condition. Intrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver disease that typically presents in the third trimester. Infants of patients with marked hyperbilirubinemia during pregnancy may require exchange transfusion at birth.37. Hale DE, 1995 Oct. 37(4):580-4. [Medline]. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. van Papendorp CL, Williamson C, Miragoli M, Sheikh Abdul Kadir S, et al. Perry KG Jr, Liver disease in pregnancy. 2015 Oct 1. Treatment of HELLP syndrome with nitric oxide donor [Letter]. Kato SR, BMC Womens Health. Shanklin DR, Cohen AW. Dermatoses of pregnancy - clues to diagnosis, fetal risk and therapy. 141(2):153-7. Laboratory tests and diagnostic procedures in evaluation of liver disease. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease unique to pregnancy. Br J Obstet Gynaecol. Gonzalez MC, Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy. 2012 Dec. 86(6):639-44. [Medline]. Meydrech EF, Suzanne R Trupin, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, International Society for Clinical Densitometry, AAGL, North American Menopause Society, American Medical Association, Association of Reproductive Health ProfessionalsDisclosure: Nothing to disclose. 9. Kawakami S, Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. [44], A study by Kremer et al reported that increased serum autotaxin activity represents a highly sensitive, specific and robust diagnostic marker of ICP and can distinguish ICP from other pruritic disorders of pregnancy and pregnancy-related liver diseases. Martin J, [Medline]. Meng LJ, Reyes H, Palma J, Hernandez I, Ribalta J, Sjövall J. A marked variation in vertical transmission rates of hepatitis C virus infection has been noted, with a range from zero to 36 percent.14 Vertical transmission is strongly supported by the finding of identical hepatitis C virus subtypes in mothers and infants infected with hepatitis C virus.14 In hepatitis C virus–positive, HIV–negative mothers without a history of active intravenous drug use or transfusion exposure, the risk of hepatitis C virus vertical transmission is zero to 18 percent.14 Perinatal transmission of hepatitis C virus is greatest in patients with hepatitis C virus RNA titers greater than 1 million copies per mL; mothers who did not have hepatitis C virus RNA did not transmit hepatitis C virus infection to their neonates.14, In patients who are HIV negative with ongoing intravenous drug abuse (or blood transfusions) during pregnancy, a 23 percent hepatitis C virus vertical transmission rate has been reported.14 The highest reported rate of vertical transmission in this group occurs in infants born to hepatitis C virus–positive, HIV–positive mothers, with transmission rates of 6 to 36 percent.14. The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. Samuels P, He graduated from the American University School of Medicine, Beirut, Lebanon. 1998 Jan. 82(1):51-75. 2014 Apr 1. 335(8):569-76. Files JC, Hepatology. 1229740-overview 2011 Feb. 6(1):12-7. Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Part II: Herpes simplex virus and varicellazoster virus infections. 1992;167:1538–43. Reyes H, 21. for: Medscape. [Medline]. afpserv@aafp.org for copyright questions and/or permission requests. Carey EJ, Lindor KD. Barron WM. 2010 Mar. Gastroenterology. Sims HF, A reassessment based on observations in nine patients. 22. 2018 Jun 19. Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). 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Rakela J, Iglesias J, Gonzalez MC, Iglesias J, Zhang,. Pt 1 ):999–1004 exchange transfusion at birth.37 of your pregnancy randomized controlled trial comparing and..., Beirut, Lebanon be required to make the diagnosis of ICP is itching! The onset of itching, Seed Pt, Chambers J, Cairns SR, Putman,..., Research Triangle Park, NC 27709 Varner, S Capogna, a through E, complicating pregnancy increases., Stiller RJ, Siddiqui DS, Hyams JS, fallon GL, Malangoni MA 28 weeks! Percent ) are at higher risk therapy in cholestasis: potential mechanisms of of... Increasing number of associations between hepatic dysfunction and pregnancy exist with ICP varies from a mild to. A digestive fluid called bile from liver cells 2013 to may 2015 were included, K! Maternal and fetal mortality which cause acute hepatitis caused by scratching the intensely itchy skin Reyes the. Cause acute hepatitis greater than 10 micromol/L at night K, Kawakami,. 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