Changes in Serum Bile Acid Concentrations During Normal Pregnancy, in Patients With Intrahepatic Cholestasis of Pregnancy and in Pregnant Women With Itching

Heikkinen, Jorma; Mäentausta, O.; Ylöstalo, Pekka; Jänne, Olli A.

doi:10.1111/j.1471-0528.1981.tb00975.x

Cited by 133 publications

(71 citation statements)

References 16 publications

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“…20,21,24,25 We found tBA to be increased in 63%, ALT in 64%, and AST in 80% of women with ICP (at diagnosis), whereas others have reported tBA and ALT to be elevated in 92% to 100% and 50% to 100% of ICP cases, respectively. 1,20,21,26 Part of this variability highlights the problem of a consistent definition for ICP, particularly in earlier series. The magnitude of elevations in tBA were lower than those of ALT activity or GSTA concentrations in our study, further supporting the use of the latter.…”

Section: Discussionmentioning

confidence: 74%

Glutathione S –Transferase and Liver Function in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

et al. 2004

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Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n ‫؍‬ 63), PG (n ‫؍‬ 43), and normal pregnant controls (n ‫؍‬ 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (؎2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, ␥-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

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Section: Discussionmentioning

confidence: 74%

Glutathione S –Transferase and Liver Function in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

et al. 2004

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“…Although liver transaminases can be elevated in ICP, total serum bile acid concentration appears to be the most specific laboratory evidence for the presence of ICP. 21,22 To our knowledge, there is no validated method to measure pruritus in ICP. Our decision to use a 10-point visual analog scale was to provide our subjects an easy unidimensional method to rate their pruritus; pruritus is most commonly measured using a 10-point scale.…”

Section: Resultsmentioning

confidence: 99%

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population

et al. 2006

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Objective: To establish the prevalence of intrahepatic cholestasis of pregnancy (ICP) in a primarily Latina population in the United States.Study design: Over a period of 16 months, a convenience sample of subjects admitted to labor and delivery in the third trimester was enrolled. Each subject completed a questionnaire rating their severity of pruritus on a numeric scale of 1 to 10. Serum was analyzed via radioimmunoassay for total bile acid concentration. ICP was defined as pruritus score >4 and a total serum bile acid concentration of X20 mmol/l. Ethnicity was determined from hospital record demographic data.Results: All invited participants enrolled in the study. Three hundred and forty subjects were enrolled. Three hundred and sixteen subjects (93%) were identified as Latina. The serum bile acid concentration range for the entire study population was 1 to 580 mmol/l with a mean of 10.4±34.9 mmol/l. Twenty-four (7.1%) subjects had a serum bile acid concentration X20 mmol/l. A pruritus score >4 was found in 19.7% (67/ 340). Of the 24 subjects with a bile acid concentration X20 mmol/l, 19 also had a pruritus score >4. Thus, the prevalence of ICP in this population was 5.6% (19/340). In subjects with ICP, the mean serum bile acid concentration was 89.5±124.0 mmol/l. When controlling for confounders, women with ICP were associated with higher rates of chorioamnionitis (P ¼ 0.043) and their fetuses had higher rates of thick meconium (P ¼ 0.053). Conclusions:The overall prevalence of ICP in this population was 5.6%, 10 to 100 times higher than previously reported data from the United States. Larger studies of perinatal morbidity examining the diagnostic criteria of cholestasis need to be conducted.

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“…In normal pregnancy, serum bile acid levels do not change significantly during the course of the pregnancy, 22,23 although one study has reported reduced levels in the first trimester. 24 Cholic acid is the primary bile acid in pregnant women, while chenodeoxycholic acid and deoxycholic acid predominate in nonpregnant women.…”

Section: Discussionmentioning

confidence: 99%

Basic science: Genes encoding bile acid, phospholipid and anion transporters are expressed in a human fetal cardiomyocyte culture

Gorelik

Patel

Ng'andwe

et al. 2006

BJOG

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Objectives To establish a human fetal cardiomyocyte culture and to investigate whether the genes that encode transporters that may influence influx or efflux of bile acids are expressed in human fetal cardiomyocytes. Design Laboratory study. Setting Imperial College London. Sample Six fetal hearts were obtained at the time of termination of pregnancy at 12–13 weeks of gestation and used to generate primary human cardiomyocyte cultures. Methods To confirm the presence of cardiomyocytes, the cells were incubated with monoclonal antibodies to sarcomeric α‐actinin and anticardiac myosin heavy chain. Real‐time reverse transcription polymerase chain reaction was used to establish whether transcripts of genes that may influence bile acid transport are present in the culture (NTCP, BSEP, MDR3, FIC1, MRP2, MRP3, OATP‐A, OATP‐C, OATP‐D, OATP‐E) and whether taurocholate administration alters messenger RNA (mRNA) expression. Main outcome measures Relative mRNA expression of genes of interest. Results Real‐time polymerase chain reaction demonstrated the presence of mRNA for BSEP, MDR3, FIC1, OATP‐C, OATP‐D and OATP‐E in fetal heart. Four transcripts remained in the cardiomyocyte culture (BSEP, MDR3, FIC1 and OATP‐D), and we demonstrated the influence of taurocholate on gene expression. Conclusions We have developed an in vitro model of the fetal heart that may be used for studies of the cardiac effect of endobiotics, e.g. bile acids, or of specific agents that may be used to treat the mother or fetus in pregnancy.

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Changes in Serum Bile Acid Concentrations During Normal Pregnancy, in Patients With Intrahepatic Cholestasis of Pregnancy and in Pregnant Women With Itching

Cited by 133 publications

References 16 publications

Glutathione S –Transferase and Liver Function in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

Glutathione S –Transferase and Liver Function in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population

Basic science: Genes encoding bile acid, phospholipid and anion transporters are expressed in a human fetal cardiomyocyte culture

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