Intrahepatic Cholestasis of Pregnancy Leading to Severe Vitamin K Deficiency and Coagulopathy

Maldonado, Maria C.; Alhousseini, Ali; Awadalla, Michael S.; Idler, Jay; Welch, Robert; Puder, Karoline S.; Patwardhan, Manasi; Gonik, Bernard

doi:10.1155/2017/5646247

Cited by 17 publications

(22 citation statements)

References 7 publications

(14 reference statements)

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“…However, it is ineffective in decreasing ALT levels and pruritus in ICP patients [42,43]. A common practice is the induction of labor at the 36th–38th week of gestation to lower the risk of intrauterine death [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19].…”

Section: Discussionmentioning

confidence: 99%

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Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester

et al. 2019

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Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 μmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.

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Section: Discussionmentioning

confidence: 99%

“…The reason is that ICP causes impaired absorption of fat-soluble vitamins (D, E, A, K) from the terminal ileum, due to altered enterohepatic circulation of bile acids. As the most important vitamin for coagulation, vitamin K is synthesized by the mother, and the fetus takes it by transplacental passage [14].…”

Section: Introductionmentioning

confidence: 99%

Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester

et al. 2019

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“…The high-level cholic acid, especially high CG, in pregnant women with ICP, may cause the shrinkage of the placental villus (16), thus, resulting in edema of the placental trophocytes. Despite the increased number, edema occurs in the basal villus, and the villous cavity remarkably declines (17), thus causing a significant reduction of maternal blood flow in the placental villus cavity, fetal hypoxia and intrauterine distress (18).…”

Section: Discussionmentioning

confidence: 99%

Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes

Wang

Zhou

et al. 2019

Exp Ther Med

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The effects of intrahepatic cholestasis of pregnancy (ICP) on hepatic function, changes of inflammatory cytokines and fetal outcomes were studied. In total, 663 pregnant women admitted to Daqing Longnan Hospital from July 2016 to December 2017 were selected. There were, 40 cases with ICP enrolled in the observation group, and 40 normal pregnant women were recruited in the normal group. They were also grouped according to hepatic function and inflammatory cytokines, with 40 cases in each group. Neonatal Apgar scores were recorded. The correlations of serum cholylglycine (CG) in pregnant women with umbilical artery systolic-to-diastolic (S/D) ratio in the third trimester of pregnancy, the alanine aminotransferase level, the high-sensitivity C-reactive protein (hs-CRP) level, neonatal Apgar score and gestational week were analyzed. The birth weight in the observation group was lighter than that in the normal group (P<0.05); the gestational week at birth was earlier than that in the normal group (P<0.05); Apgar score at birth was lower than that in the normal group (P<0.05), and the levels of inflammatory cytokines were higher than those in the control group (P<0.05). Apgar scores of newborns at birth and at 1 and 5 min after birth in the normal hepatic function and normal inflammatory cytokine groups were higher than those in the abnormal hepatic function group (P<0.05). The serum CG level in pregnant women was positively correlated with umbilical artery S/D ratio, the alanine aminotransferase level and the hs-CRP level in the third trimester of pregnancy, but negatively correlated with neonatal Apgar score and gestational week. Among patients with ICP, the higher the GG level in the body is, the higher the alanine aminotransferase, inflammatory cytokine and umbilical artery S/D ratio will be, which may cause lower neonatal Apgar score, neonatal asphyxia and premature delivery.

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“…The biological significance of VK for the regulation of bile acids synthesis is not clear, but recently, Maldonado et al reported that VK deficiency is associated with intrahepatic cholestasis of pregnancy in certain patients. Low levels of VK may cause dysregulation of bile acid synthesis with concomitant upregulation of CYP7A1 and CYP8B1 expression levels, which occurs during the progression of this disease [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Vitamin K2 on the Expression of Genes Involved in Bile Acid Synthesis and Glucose Homeostasis in Mice with Humanized PXR

et al. 2018

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Pregnane X receptor (PXR) is a nuclear receptor activated by various compounds, including prescribed drugs and dietary ingredients. Ligand-specific activation of PXR alters drug metabolism and affects many other physiological conditions. Species-specific ligand preference is a considerable challenge for studies of PXR function. To increase translational value of the results of mouse studies, humanized mouse model expressing human PXR (hPXR) has been developed. Menaquinone-4 (MK-4), one of vitamin K2 analogs prescribed in osteoporosis, is a PXR ligand. We hypothesized that MK-4 could modulate the physiological conditions endogenously influenced by PXR, including those that have not been yet properly elucidated. In the present study, we investigated the effects of a single oral treatment with MK-4 on hepatic gene expression in wild-type and hPXR mice by using quantitative RT-PCR and DNA microarray. MK-4 administration altered mRNA levels of genes involved in drug metabolism (Abca3, Cyp2s1, Sult1b1), bile acid synthesis (Cyp7a1, Cyp8b1), and energy homeostasis (Aldoc, Slc2a5). Similar mRNA changes of CYP7A1 and CYP8B1 were observed in human hepatocarcinoma HepG2 cells treated with MK-4. These results suggest that MK-4 may modulate bile acid synthesis. To our knowledge, this is the first report showing the effect of MK-4 in hPXR mice.

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Intrahepatic Cholestasis of Pregnancy Leading to Severe Vitamin K Deficiency and Coagulopathy

Cited by 17 publications

References 7 publications

Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester

Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester

Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes

Effects of Vitamin K2 on the Expression of Genes Involved in Bile Acid Synthesis and Glucose Homeostasis in Mice with Humanized PXR

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