A T Dann

Longitudinal Profiles of 15 Serum Bile Acids in Patients With Intrahepatic Cholestasis of Pregnancy

OBJECTIVES:Increased maternal serum bile acids are implicated in intrahepatic cholestasis of pregnancy. Individual bile acid profiles and their relationship with disease progression, however, remain unknown. The purpose of this prospective study was to determine the temporal changes in bile acids in normal pregnancy and in pregnancies complicated with intrahepatic cholestasis of pregnancy and pruritus gravidarum.METHODS:A validated method for the evaluation of 15 bile acids (conjugated and unconjugated) in a single serum sample was developed using high-performance liquid chromatography/mass spectrometry (HPLC-MS) with an electrospray interface. Bile acid concentrations were assessed in samples (16 weeks of gestation to 4 weeks postpartum) from women with, or who later developed, intrahepatic cholestasis of pregnancy (n=63) and were compared with those from normal pregnant women (n=26) and from women with pruritus gravidarum (n=43).RESULTS:Intrahepatic cholestasis of pregnancy was associated with a predominant increase in cholic acid conjugated with taurine and glycine, from 24 weeks of pregnancy. Ursodeoxycholic acid (UDCA) treatment (≥21 days, n=15) significantly reduced serum taurocholic and taurodeoxycholic acid concentrations (P<0.01). Bile acid profiles were similar in normal pregnancy and pregnancy associated with pruritus gravidarum.CONCLUSIONS:The bile acid profiles and effects of treatment by UDCA implicate a role for taurine-conjugated bile acids in the syndrome of intracranial pressure. With regard to individual bile acid profiles, pruritus gravidarum is a disorder quite distinct from intrahepatic cholestasis of pregnancy.

Plasma lipid profiles of women with intrahepatic cholestasis of pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy is associated with dyslipidemia, but the gestational lipid profile in relation to clinical diagnosis of the disease is unknown. The aim of this study was to undertake a detailed analysis of plasma lipids in women presenting with intrahepatic cholestasis of pregnancy and pruritus gravidarum. METHODS: Plasma lipid concentrations were assessed in nonfasting blood samples from 63 women with intrahepatic cholestasis of pregnancy (n = 54, recruited at the time of diagnosis, and n = 9, who later developed the disease), 43 women with pruritus gravidarum, and 26 healthy pregnant controls during pregnancy and at 4–6 weeks postpartum. RESULTS: Intrahepatic cholestasis of pregnancy was associated with an abnormal lipid profile. Low-density lipoprotein (LDL) cholesterol, apolipoprotein B-100, and total cholesterol concentrations were significantly raised during pregnancy in women with intrahepatic cholestasis of pregnancy compared with pruritus gravidarum and controls, and LDL-cholesterol was raised before clinical diagnosis. High-density lipoprotein cholesterol was lower in women with intrahepatic cholestasis of pregnancy compared with the pruritus gravidarum group. Ursodeoxycholic acid did not alter plasma lipid concentrations. CONCLUSION: Intrahepatic cholestasis is associated with dyslipidemia, which may contribute to the pathogenesis of the disease. The elevation of LDL cholesterol and reduction of high-density lipoprotein cholesterol before clinical diagnosis may prove to be a useful biomarker for the early identification of intrahepatic cholestasis of pregnancy and differentiation from pruritus gravidarum. LEVEL OF EVIDENCE: II-2

Glutathione S‐transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum

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, γ‐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. (HEPATOLOGY 2004;40:1406–1414.)

Cord liver function and bile acids in actively managed obstetric cholestasis (OC) are not abnormal

Obstetric cholestasis (OC) is associated with increased fetal morbidity and mortality. Active management (delivery by 38 weeks) may reduce this. Poor fetal outcome may be linked to high concentrations of bile acids in the maternal or fetal circulation. This study compared maternal and fetal liver function in a group of actively managed women with OC. Matched cord and maternal (day of delivery) serum was obtained from women with: (i) OC [n = 43, 16 ursodeoxycholic acid (UDCA)], (ii) pruritus gravidarum (PG, n = 28) and (iii) healthy controls (n = 9). Women with OC were delivered by 38 weeks; there were no stillbirths. Bile acids, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutathione S-transferase alpha 1-1 (GSTA1-1) were measured. Maternal liver function parameters were raised in OC and not reduced significantly by UDCA treatment (P = 0.748, 95% CI= 0.934–1.099). In OC, cord serum liver function values were no different to controls and PG. Cord serum ALT, AST and GSTA1-1 in OC were lower than the maternal serum. Cord serum bile acid concentrations (µm) in the OC group were 16.97 ± 1.13 and in maternal blood 18.57 ± 3.20 compared to 12.89 ± 1.00 and 7.24 ± 1.2 in PG and 15.99 ± 1.95 and 6.76 ± 0.96 in controls, respectively.