Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: a randomized controlled trial.

PURPOSE: To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: In the randomized (double-blind, placebo-controlled) study 20 pregnant women with ICP received (random allocation of) either 450 mg/day UDCA or placebo for 14 days during the third trimester of pregnancy. The severity of pruritus was registered and itching scores were assessed before the treatment and weekly thereafter. The effects of UDCA on liver function and fetoplacental hormone production were measured with covering laboratory testing: serum levels of alanine aminotransferase (ALAT), total bile acids (TBA), estradiol, progesterone, prolactin, cholesterol, HDL-cholesterol, triglycerides, activated partial thromboplastin time, fibrinogen D-dimers (FIDD) and platelet count were assessed before the treatment and weekly thereafter. Data on pregnancy and delivery outcome were recorded and analyzed. RESULTS: UDCA was well tolerated. A significant improvement in itching scores was detected in 2 weeks in the group receiving UDCA. Serum levels of ALAT and TBA fell after 2 weeks treatment. The other laboratory values were not modified by the treatment. CONCLUSIONS: UDCA improves maternal itching scores and liver function tests without interfering with the fetoplacental estrogen production in patients with ICP. UDCA is well tolerated by pregnant women. No fetal or neonatal side-effects could be detected.

Hepatocellular enzyme glutathione S-transferase alpha and intrahepatic cholestasis of pregnancy.

OBJECTIVE: To evaluate and compare plasma glutathione S-transferase alpha (GSTA) concentrations in the third trimester of pregnancy in patients with intrahepatic cholestasis of pregnancy (ICP) and in healthy pregnant women. DESIGN: Non-randomized clinical study. SETTING: Maternity unit and Department of Clinical Chemistry, Turku University Central Hospital, Turku, Finland. POPULATION: Twenty-seven women with ICP and 49 healthy pregnant women. METHODS: GSTA concentrations were assessed in plasma samples in the third trimester of pregnancy using an enzyme-linked immunoassay (HEPKIT Alpha, Biotrin, Sinsheim-Reihen, Germany). MAIN OUTCOME MEASURES: Plasma GSTA, serum alanine and bile acid concentrations were compared between study and control group. Correlation between plasma GSTA levels and serum alanine aminotransferase and bile acid levels in the ICP patients were tested by Spearman correlation coefficients. Main perinatal outcome was compared between the groups. RESULTS: GSTA concentration in the control group was 1.62 microg/l (range: 0.25-6.1). In the ICP patients, the mean plasma GSTA concentration was 51.0 microg/l (range: 2.1-183.5), the mean serum alanine aminotransferase concentration was 145.70 U/l (range: 6-393) and the mean bile acid concentration was 19.2 micromol/l (range: 3-63). There was a statistically significant correlation in ICP patients between plasma GSTA concentration and serum alanine aminotransferase concentration (r=0.694, p=0.0001), but not with serum bile acid concentration. Nor was there any statistically significant correlation between gestational weeks and plasma GSTA concentration in the study group. CONCLUSION: Plasma GSTA measurements may provide a more sensitive and specific diagnostic tool for diagnosis of ICP than the evaluation of transaminases or bile acid concentrations alone. Further studies are needed to evaluate the role of GSTA in the follow-up of patients with ICP and its prognostic value for threatening fetal distress in patients with ICP.