Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. [Effect of integrative Chinese and Western medicine in treating pregnant women with intrahepatic cholestasis]. Ursodeoxycholic acid therapy in pregnant women with cholestasis. S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial. [Analysis on therapeutic effect of Western and Chinese drug in treating intrahepatic cholestasis pregnancy]. Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. [Observation on effect of danxiaoling in supplementary treatment of intrahepatic cholestasis in pregnancy]. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.
Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP. To evaluate the therapeutic effect of compound salvia injection combined with ursodeoxycholic acid (UDCA) in treating pregnant women with intrahepatic cholestasis (ICP) and its influence on perinatal babies.
                One hundred and twenty-eight patients of ICP were assigned to two groups. The 72 patients in the treatment group were treated with salvia injection (20 mL in 10% glucose 500 mL for intravenous dripping once a day) and UDCA (15 mg, thrice daily by oral taken), and the 56 patients in the control group were treated with UDCA alone, all were treated for 14 days. Changes of itching symptom (estimated by scoring) and serum levels of biochemical indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and glycocholic acid (GCA), were determined before and after treatment, and conditions of the newborns were compared after delivery.
                Compared with before treatment, scores of itching were lowered from 3.6 scores to 1.4 scores in the treatment group, and from 3.4 scores to 1.6 scores in the control group, showing no significant difference between groups (P > 0.05), but the lowering was shown earlier in the former. Levels of biochemical indexes were improved significantly (P < 0.01) in both groups, but the improvements were more significant in the treatment group, the difference between groups was significant (P < 0.05). The difference between groups in the incidence of fetal distress, meconium-stained fluid and neonatal asphyxia were insignificant (P > 0.05). The birth weights of the newborns were higher in the treatment group than in the control group (3,108 +/- 236 g vs 2,681 +/- 269 g, P < 0.05).
                The combined therapy of compound salvia injection and UDCA shows better effect in treating ICP than that of UDCA alone. To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP) by a randomized, double-blind, placebo-controlled trial.
                Eight patients with pruritus and abnormal liver function tests received 600 mg/day of UDCA in two doses for 20 days, compared with a control group of eight patients who received placebo for 20 days.
                No adverse reactions were detected in any patient. During UDCA therapy a statistically significant improvement in pruritus, serum bile salt levels, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and total and direct bilirubin was observed. Only two patients treated with UDCA underwent cesarean sections due to reasons unrelated to the therapeutic trial. All newborns had an Apgar score >7 and normal postnatal growth.
                Although the number of patients in this study was very small, we suggest that UDCA treatment has a role in improving clinical and biochemical results in ICP. To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP).
                Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases.
                After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups.
                These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials. To evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy (ICP) and improving prognosis of perinatal newborn babies.
                Sixty in-patients of ICP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treatment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery.
                After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P < 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P > 0.05).
                Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading. To compare the efficacy of the ursodeoxycholic acid (UDCA) and S-adenosyl-L-methionine (SAMe) monotherapy with their combined effect on intrahepatic cholestasis of pregnancy (ICP).
                We studied singleton pregnancies at <36 weeks with a moderate or severe form of ICP between January 1999 and March 2004. Patients were randomized to either oral UDCA 3x250 mg daily or 500 mg SAMe twice daily in slow running infusion for twelve days followed by oral administration of 500 mg twice daily until delivery. Intensive hematological, biochemical and fetal monitoring were carried out.
                Of the 78 women enrolled, 25 received SAMe monotherapy, 26 received UDCA, and 27 received combined therapy. Groups were initially comparable in terms of gestational age, duration of therapy, parity and biochemical characteristics. All therapies improved the pruritus. The combined therapy and the monotherapy with UDCA (later) led to improving of the serum concentrations of bile acids and transaminases compared with SAMe monotherapy (P<0.01). Combined therapy led to a faster decrease of serum concentrations of bile acids and transaminases compared with UDCA monotherapy (borderline significance). Gestational ages were similar in all groups. No adverse effects were noted on the fetuses or neonates with either therapy.
                UDCA is an effective drug in the treatment of ICP, and combined with SAMe, has probably a synergistic effect on biochemical parameters. This mode of treatment seems more effective but the effect of the successful treatment on the fetus is unclear. Therefore, the ante- and intrapartum monitoring of the fetus should be part of the management of severe forms of ICP. The project is supported by IGA MZ CR (No. NH/7376-3). To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions.
                First phase of a semifactorial randomised controlled trial.
                Nine consultant led maternity units, United Kingdom.
                125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks' gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management.
                Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks' gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks' gestation).
                The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates.
                Ursodeoxycholic acid reduced itching by -16 mm (95% confidence interval -27 mm to -6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval -3 to 34); this would represent a number needed to treat of 6, but it failed to reach significance. Early term delivery did not increase caesarean sections (7/30 (23%) in the early term delivery group versus 11/32 (33%) in the expectant management group (relative risk 0.70, 95% confidence interval 0.31 to 1.57). No serious harms were noted in either trial. 22% (73/325) of eligible women participated in the drug trial and 19% (39/209) in the timing of delivery trial; both groups had a similar spectrum of disease severity to non-participants.
                Ursodeoxycholic acid significantly reduces pruritus, but the size of the benefit may be too small for most doctors to recommend it, or for most women to want to take it. Women are, however, likely to differ in whether they consider the benefit to be worthwhile. Planned early term delivery seems not to increase incidence of caesarean section, although a small increase cannot be excluded. A trial to test whether ursodeoxycholic acid reduces adverse perinatal outcomes would have to be large, but is feasible. A trial to test the effect of early term delivery on adverse fetal outcomes would have to be significantly larger and may not be feasible.
                Current Controlled Trials ISRCTN37730443. To evaluate the curative effect of Danxiaoling Pill (DXLP), a Chinese herbal preparation, in treating intrahepatic cholestasis in pregnancy (ICP).
                Fifty-eight cases of ICP were divided randomly into two groups and treated by DXLP and Composite Yiganling as control respectively with the other identical conventional treatment. The changes of clinical symptoms, related laboratory parameters after treatment and the condition of labor were observed.
                The total effective rate in both groups was 100%, but the markedly effective rate in the DXLP treated group was higher than that in control group (P < 0.01). Levels of blood cholyglycine acid (CGA), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, total cholesterol and low density lipoprotein were all decreased in both groups after treatment, but DXL showed a better efficacy in decreasing CGA, ALT and AST than that of Yiganling. Moreover, the amniotic fluid meconium contaminated rate, premature delivery occurrence in the DXLP group were lower than those in the control group, while the weight of newborn baby was higher in the former than in the latter.
                DXLP could effectively lower the serum bile acid and improve liver function in treating ICP. Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset.
                Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery.
                Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery.
                Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.
Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.
A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.
There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.