[Intrahepatic cholestasis of pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice]. / La cholestase gravidique : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies for reducing neonatal and maternal morbidity associated with intrahepatic cholestasis pregnancy (ICP). MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 14 questions (from 12 PICO questions and one definition question outside the PICO format), there was agreement between the working group and the external reviewers on 14 (100%). The level of evidence of the literature was insufficient to provide a recommendation on two questions. ICP is defined by the occurrence of suggestive pruritus (palmoplantar, nocturnal) associated with a total bile acid level>10µmol/L or an alanine transaminase level above 2N after ruling out differential diagnoses. In the absence of suggestive symptoms of a differential diagnosis, it is recommended not to carry out additional biological or ultrasound tests. In women with CIP, ursodeoxycholic acid is recommended to reduce the intensity of maternal pruritus (Strong recommendation. Quality of the evidence moderate) and to decrease the level of total bile acids and alanine transaminases. (Strong recommendation. Quality of the evidence moderate). S-adenosyl-methionine, dexamethasone, guar gum or activated charcoal should not be used to reduce the intensity of maternal pruritus (Strong recommendation. Quality of evidence low), and there is insufficient data to recommend the use of antihistamines (No recommendation. Quality of evidence low). Rifampicin (Weak recommendation. Very low quality of evidence) or plasma exchange (Strong recommendation. Very low quality of evidence) should not be used to reduce maternal pruritus and perinatal morbidity. Serum monitoring of bile acids is recommended to reduce perinatal morbidity and mortality (stillbirth, prematurity) (Low recommendation. Quality of the evidence low). The level of evidence is insufficient to determine whether fetal heart rate or fetal ultrasound monitoring are useful to reduce perinatal morbidity (No recommendation). Birth is recommended when bile acid level is above 99µmol/L from 36 weeks gestation to reduce perinatal morbidity, in particular stillbirth. When bile acid level is above 99µmol/L is below 100µmol/L, women should be informed that induction of labor could be considered 37 and 39 weeks gestation to reduce perinatal morbidity. (Strong recommendation. Quality of evidence low). In postpartum, total bile acids and alanine transaminases level should be checked and normalized before prescribing estrogen-progestin contraception, ideally with a low estrogen dose (risk of recurrence of pruritus and cytolysis) (Low recommendation. Quality of evidence very low). CONCLUSION: Although the quality of evidence regarding ICP gestational cholestasis remains low, there is a strong consensus in France, as shown by our Delphi study, on how to manage women with ICP. The reference first-line treatment is ursodeoxycholic acid.

The effectiveness of small heterodimer partner and FGF 19 levels in prediction of perinatal morbidity in intrahepatic cholestasis of pregnancy.

Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules responsible for controlling serum bile acid levels. We designed this study for evaluating the effects of FGF 19 and SHP in intrahepatic cholestasis of pregnancy (ICP). Fifty-six pregnant women having ICP and 20 healthy pregnant women were included in the study. The patients were followed up until delivery in terms of pregnancy-related morbidity/mortality. Serum FGF 19 and SHP levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group (p: .04, p: .003, respectively). In ROC analysis, SHP level above 1995 ng/L was found effective in predicting the need for neonatal intensive care unit (ICU) follow-up with 53.8% sensitivity and 77.8% specificity. High SHP levels were correlated with perinatal morbidity, mortality and neonatal ICU hospitalisation.Impact StatementWhat is already known on this subject? Itching, elevated serum transaminase and serum total bile acid (TBA) levels are the most important clinical and biochemical findings of intrahepatic cholestasis of pregnancy (ICP). Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules - responsible for controlling serum bile acid levels. ICP is associated with preterm labour, asphyxia, foetal distress, stillbirth and preeclampsia.What do the results of this study add? Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group. High SHP level was found effective in predicting the need for neonatal intensive care unit and showed a negative correlation with birth week and birth weight.What are the implications of these findings for clinical practice and/or further research? Checking SHP levels can help to predict perinatal mortality and morbidity. Treatments to be developed through the mechanism of action of FGF 19 and SHP can be promising in the treatment of ICP and other cholestatic liver diseases.

Maternal serum, placental, and umbilical venous blood irisin levels in intrahepatic cholestasis of pregnancy.

OBJECTIVE: To explore the changes of serum, umbilical vein, placental irisin level, and the correlation between irisin level and relevant indicators in pregnant women with intrahepatic cholestasis of pregnancy (ICP), so as to provide a new perspective for in-depth studies on the causes and treatment of ICP. METHODS: This cross-sectional case-control study method, the serum, umbilical venous blood irisin, liver, kidney function, lipid metabolism, and other indicators of 108 normal pregnant women, 64 patients with mild ICP, and 39 patients with severe ICP were compared, and the changes in the levels of oxidative stress and irisin were observed by dihydroethidium staining and immunohistochemistry. RESULTS: The level of placental oxidative stress in severe ICP group and mild ICP group was significantly higher than that in normal pregnant women group, and the mild ICP group was significantly higher than that in severe ICP group (p < .05); the concentration of irisin in umbilical vein was significantly lower than that in peripheral blood; the serum irisin of normal pregnant women (918.51 ± 159.90 pg/ml) was significantly lower than that of pregnant women with mild ICP (1030.05 ± 137.98 pg/ml) and pregnant women with severe ICP (1094.34 ± 154.35 pg/ml). The concentration of irisin in umbilical vein blood of pregnant women with severe ICP (858.78 ± 97.42 pg/ml) was significantly higher than that of normal pregnant women (595.33 ± 162.70 pg/ml) and those with mild ICP (648.82 ± 164.81 pg/ml) (p < .05). Irisin was expressed in placental tissues of normal pregnant women group, mild ICP group and severe ICP group, and the differences were statistically significant in expression intensity of the three groups (χ2 = 19.959, p < .05). The irisin expression intensity in the ICP group was higher than that in the control group, and the irisin expression intensity in the ICP group was higher than that in the ICP group (ß = 0.292; t = 3.063; p < .05). At the best cutoff level of 989.168 pg/ml, irisin accurately predicted ICP [AUC = 0.622 (95%CI 0.543-0.701, p < .05)] with sensitivity and specificity rates of 60.9 and 40.1%, respectively. CONCLUSION: Irisin can reduce the level of oxidative stress and improve lipid metabolism in ICP patients during the pathophysiological process of ICP, and it is possible to become a new auxiliary factor of ICP diagnosis and indexing.

Frequency of intrahepatic cholestasis of pregnancy in Punjab Pakistan: A single centre study.

OBJECTIVE: To find out the frequency of intrahepatic cholestasis of pregnancy and its identification parameters. METHODS: The cross-sectional observational study was conducted in the Department of Medicine and the Department of Obstetrics, Combined Military Hospital, Kharian, from October 2013 to March 2014, and comprised all pregnant patients having symptoms suggestive of intrahepatic cholestasis which was confirmed after systemic inquiry, examination and biochemical analysis. Patients with cholestasis due to another reason, coagulopathies, thrombocytopenia and tumours were excluded. The patients were followed up till delivery to see the effects of cholestasis on mother and child. RESULTS: Out of 1001 obstetric patients, 31(3.1%) had intrahepatic cholestasis of pregnancy. Pruritus was the main symptom in 25 (85%) patients followed by rash in 20 (65%). In 20 (64%) patients, labour was induced. Mode of delivery was Caesarean Section in 18 (58%) patients and 9 (29%) had postpartum haemorrhage. Regarding neonatal complications, 22 (70%) required admission to neonatal intensive care and 15 (48%) had meconium aspiration. CONCLUSIONS: A high frequency of intrahepatic cholestasis of pregnancy was observed. It had significant impact on maternal and foetal health.

Clinical Study of S-Adenosyl-L-Methionine Combined with Ursodeoxycholic Acid in Treatment of 40 Cases with Intrahepatic Cholestasis of Pregnancy / 医药导报

Objective To observe the clinical effects and the safety of S-adenosy-L-methionine ( SAMe ) associated with ursodeoxycholic acid (UDCA) in treating intrahepatic cholestasis of pregnancy (ICP). Methods Eighty patients with ICP were randomly divided into treatment group ( treated with UDCA orally, 250 mg, TID and simultaneously with intravenous SAMe 1. 0 g, qd) and control group (treated with intravenous SAMe 1. 0 g, qd). Pruritus degree, serum total bilirubin (TB), total bile acid (TBA), glycocholic acid (CG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed before and after the treatment, and the pregnancy outcomes, such as the rate of premature, uterine-incision delivery and fetal distress were recorded. Results After treatment, the pruritus degree and the levels of TB, TBA, CG, ALT AST were decreased significantly compared with pretreatment in both groups. TB, TBA, AST and ALT of the treatment group decreased from (27.83±9. 34), (45. 62±18. 30) μmol·L-1, (195. 98±30. 22), (188. 69±29. 11) U·L-1 to (11. 81±4. 91), (11. 88±2. 23) μmol·L-1, (73. 59±21. 53), (67. 94±30. 53) U·L-1, respectively, and TB, TBA, AST, ALT of the control group decreased from (27. 49±7. 87), (49. 12±10. 39) μmol·L-1, (211. 93±34. 9), (210. 40±43. 39) U·L-1 to (16. 08± 6.23), (23.88±6.63) μmol·L-1, (87. 20±32. 52), (81. 77±35. 16) U·L-1, respectively (P0. 05), but the declines of TB, TBA and CG in treatment group were superior to those of the control group (P<0. 05). Conclusion In terms of improving pruritus, liver function and pregnancy outcome, single SAMe application could obtain similar effects compared with SAMe combined with UDCA, but SAMe combined with UDCA is more effective than the single SAMe application in decreasing the level of TBA and CG.