Pregnancy intrahepatic cholestasis

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Kauppila, A., Korpela, H., Makila, U-M. and Yrjanheikki, E. (1987). Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br. Med. J. 294, 150-152. 

Jacquemin E, Cresteil D, Manouvrier S, Boute O, Hadchouel M. Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. Lancet 1999 353(9148) 210-211. 

Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E et al. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy evidence for a defect in protein trafficking. Hum Mol Genet 2000 9(8) 1209-1217. 

Back P, Siovall J, Siovall (1974) Monohydroxy bile acids in plasma in intrahepatic cholestasis of pregnancy. Identification by computerized gas chromatography-mass spectrometry. Med Biol 52 31-38... 

Jaundice as a result of oral contraceptive treatment has been repeatedly described. Whereas in the Swedish population figures between 1 100 and 1 4000 were published when the early high-dose formulations were still in use (213), the overall incidence was estimated in 1979 at about 1 10 000 (9), and the current incidence is certainly further reduced. When such hepatic symptoms occur, they usually do so within the first month of medication (214), and jaundice may be accompanied by anorexia, malaise, and pruritus. Very few cases arise after the third month of medication and those reported are regarded by some as unlikely to be due to oral contraceptives. Microscopic examination of the liver shows intrahepatic cholestasis. When medication is stopped, symptoms usually disappear rapidly and the reaction does not seem to leave any sequelae (215). Genetic components seem to be important for the development of the reaction women who have experienced jaundice or severe pruritus in late pregnancy seem to be especially susceptible to jaundice or gallbladder disease when using... 

Meier PJ, Kullak-Ublick G. Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance P-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics 2004 14 91-102. 

The findings of this study suggest that women who are already jaundiced at the initiation of HRT are most at risk of increased bilirubin levels and cholestasis. In view of this it would seem sensible that, as well as assessing bilirubin levels prior to treatment, women who want to take HRT should also be assessed for any history (including family history) of jaundice. This will include specific defects in bilirubin excretion, such as intrahepatic cholestasis of pregnancy or familial conjugated hyper-bilirubinaemia, which may worsen cholestasis. 

Further intrahepatic forms of obstruction include recurrent intrahepatic cholestasis and recurrent cholestasis in pregnancy, (s. tab. 12.4)... 

Diagnosis and therapy of intrahepatic cholestasis of pregnancy (review). Zschr. Gastroenterol. 2004 42 623 - 628... 

Reyes, H. Review Intrahepatic cholestasis. A puzzling disorder of pregnancy. J. Gastroenterol. Hepatol. 1997 12 211-216... 

The clinical and biological effects and safety of urso-deoxychohc acid in intrahepatic cholestasis of pregnancy have been reported in 19 patients, 14 of whom had clinical improvement, with reduction or disappearance of pruritus, and 11 of whom had an improvement in biochemical hver function tests (13). The only birth defect reported was pyloric stenosis in a boy whose mother had taken ursodeoxychohc acid for 10 days at 34 weeks gestation. 

Berkane N, Cocheton JJ, Brehier D, Merviel P, Wolf C, Lefevre G, Uzan S. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy. A retrospective study of 19 cases. Acta Obstet Gynecol Scand 2000 79(ll) 941-6. 

Reyes, H., Ribalta, J., Gonzalez, M.C., Segovia, N., and Oberhauser, E. (1981) Sulfobromophthalein clearance tests before and after ethinyl estradiol administration, in women and men with familial history of intrahepatic cholestasis of pregnancy. Gastroenterology, 81 (2), 226-231. 

Intrahepatic cholestasis of pregnancy is a syndrome of unknown etiology characterized by a 100-fold increase in maternal and fetal blood bile salt levels. Bile salts are produced in both the fetal and maternal liver. The fetus transfers the bile salts across the placenta for disposal. When the function of the maternal gallbladder is slowed, bile salts can accumulate in the liver and bloodstream, ultimately resulting in the classical pruritus symptom. It is believed that pregnancy-related hormones may slow bile salt excretion from the gallbladder. 

Elites D. Intrahepatic cholestasis of pregnancy changes in maternal-fetal bile acid balance and improvement by ursodeoxycholic acid. Ann Hepatol 2002 l(l) 20-8. Devlin TM, ed. Textbook of Biochemistry with Clinical Correlations, 5th ed. New York Wiley-Liss, 2002. 

Germain AM, Carvajal JA, Glasinovic JC, et al. Intrahepatic cholestasis of pregnancy an intriguing pregnancy specific disorder. J Soc Gynecol Investig 2002 9(1) 10-14. 

H14. Heikkinen, J., Serum bile acids in the early diagnosis of intrahepatic cholestasis of pregnancy. Obstet. Gynecol. 61, 581-587 (1983). 

H15. Heikkinen, J., Maentausta, O., Ylostalo, P., and Janne, O., Changes in serum bile acids during normal pregnancy, in patients with intrahepatic cholestasis of pregnancy and in pregnant women with itching. Br. J. Obstet. Gynaecol. 88, 240—245 (1981). 

Cholestasis in the absence of demonstrable mechanical biliary obstruction is usually referred to as intrahepatic cholestasis, a term which implies that there is microscopic obstruction within the liver itself (P21). The condition occurs after the administration of various drugs, (see Table 10), in the presence of some infectious disorders (see Section 7.4), and during the last months of pregnancy. Mean serum alkaline phosphatase values in women with clinically overt cholestasis of pregnancy are higher than in matched controls (R13), although individual patients may have values appropriate to the last trimester of pregnancy (H2, R13). In some patients with intrahepatic cholestasis, no cause is identifiable (R35, S58). Serum alkaline phosphatase values in idiopathic cholestasis may be 7 times the upper reference limit (S75). 

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