The pathophysiology of intrahepatic cholestasis of pregnancy

Dixon, Peter H.; Williamson, Catherine

doi:10.1016/j.clinre.2015.12.008

Cited by 161 publications

(166 citation statements)

References 116 publications

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“…Estrogen may participate in the development of cholestasis [7] and progesterone may impair hepatic bile homeostasis [8]. Genetic factors are known to be involved in the pathogenesis; ICP is inherited as a sex-limited dominant phenotype and multiple genes are influential [9]. Multidrugresistant protein 3 (MDR3) is associated with up to 15% of ICP cases [10,11].…”

Section: Introductionmentioning

confidence: 99%

Intrahepatic Cholestasis of Pregnancy and Cancer: A Cohort Study

Hamalainen¹,

Turunen²,

Mattila³

et al. 2017

Fam Med Med Sci Res

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Objective: In a previous questionnaire study, more breast cancers were reported by women with intrahepatic cholestasis of pregnancy (ICP) than by the controls. The aim of this study was to establish whether ICP is associated with cancer in the Finnish Cancer Registry data, the study population being the same cohort as in the questionnaire study. Methods:The study population comprised 571 women with ICP in at least one pregnancy and 1,333 controls from Tampere University Hospital in Finland during [1969][1970][1971][1972][1973][1974][1975][1976][1977][1978][1979][1980][1981][1982][1983][1984][1985][1986][1987][1988]. The cancer data were obtained from the Finnish Cancer Registry. The cancers were classified by ICD-O-3 and diagnosed during the period 1953−2013. Results:In the ICP group, the odds ratio of cancers (OR 1.26, 95% CI 0.96-1.64), and breast cancer in particular (OR 1.36, 95% CI 0.91-2.03), was slightly higher than in the control group. Seven percent of the ICP group and 5.3% of the control group had breast cancer. Conclusion:Based on this study there is not a significant association between ICP and cancer. Earlier observation in the questionnaire study regarding association between ICP and breast cancer cannot be confirmed by this registry based study.

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Section: Introductionmentioning

confidence: 99%

Intrahepatic Cholestasis of Pregnancy and Cancer: A Cohort Study

Hamalainen¹,

Turunen²,

Mattila³

et al. 2017

Fam Med Med Sci Res

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“…In pregnant women with pruritus, sulfated progesterone metabolites are associated with itch severity and a negative effect on BA uptake and efflux. Furthermore, elevated autotaxin, a mediator of cholestatic pruritus, may be prognostic for ICP . Risk of ICP is increased with previous ICP (recurrence, 40%‐92%), history of cholestasis from oral contraceptive pills, twin pregnancies (20%), personal and familial history of gallstones, pregnancy by in vitro fertilization, history of HCV infection, low selenium, and a sister with ICP .…”

Section: Icpmentioning

confidence: 99%

“…Furthermore, elevated autotaxin, a mediator of cholestatic pruritus, may be prognostic for ICP. (48) Risk of ICP is increased with previous ICP (recurrence, 40%-92%), history of cholestasis from oral contraceptive pills, twin pregnancies (20%), personal and familial history of gallstones, pregnancy by in vitro fertilization, history of HCV infection, low selenium, and a sister with ICP. (49,50) Identifiable gene mutations occur in 20%-25% of women with ICP (Table 1; Fig.…”

Section: Icpmentioning

confidence: 99%

“…(51) Other ICP contributing factors (Fig. 4B) include reversed fetal-maternal gradient of BA (higher in mother than fetus) with an increase in BA in both mother and umbilical cord blood (cholic acid/ chenodeoxycholic acid up to 5:1), (52) placental oxidative stress, (48) and increased sulfated progesterone metabolites (partial agonists of farnesoid X receptor [FXR]), which inhibit hepatic BA uptake and efflux resulting in cholestasis. (49) Treatment with ursodeoxycholic acid (UDCA; 10-15 mg/kg) is safe and often effective for mothers.…”

Section: Icpmentioning

confidence: 99%

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Liver Diseases in the Perinatal Period: Interactions Between Mother and Infant

et al. 2020

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Liver diseases affecting the mother and infant dyad may present in the perinatal period from 20 weeks of gestation to 28 days of life. This review will focus on the current approach to neonatal acute liver failure and the progress made in the diagnosis and management of gestational alloimmune liver disease. It will highlight mother‐to‐child transmission of viral hepatitis, both management and public health implications. Emerging concepts implicating maternal obesity and nutrition in the development of a rapidly progressive nonalcoholic steatohepatitis phenotype in the offspring will be discussed. Finally, the presentation and management of acute fatty liver of pregnancy and intrahepatic cholestasis of pregnancy, and their impact on the fetus, will be reviewed.

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“…Other extrinsic pathology factors affecting human placental drug transporter expression and activity include intrahepatic cholestasis of pregnancy where the fetomaternal clearance of toxic bile acids are reversed, leading to fetal accumulation of these substances [105,106]; and the down-regulation of apical transporters and concurrent up-regulation of basal transporters during inflammatory conditions leads to decreased protection of the fetus from toxic effects of xenobiotics [107,108]. It is therefore an essential part of drug risk assessment in reproductive toxicology to understand the effects of dysregulated drug transport on human placenta accumulation and transport of compounds in the diseased state.…”

Section: Human Placental Drug Handling In Pregnancy Pathologiesmentioning

confidence: 99%

An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

Brownbill

2016

Reproductive Toxicology

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The pathophysiology of intrahepatic cholestasis of pregnancy

Cited by 161 publications

References 116 publications

Intrahepatic Cholestasis of Pregnancy and Cancer: A Cohort Study

Intrahepatic Cholestasis of Pregnancy and Cancer: A Cohort Study

Liver Diseases in the Perinatal Period: Interactions Between Mother and Infant

An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

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