9 WORLD GASTROENTEROLOGY NEWS JULY 2016 Editorial | Expert Point of View | Gastro 2016: EGHS-WGO | WDHD News | WGO & WGOF News | WGO Global Guidelines | Calendar of Events has a known role in causing cholesta-sis 3. The recurrence rate of 40–60% of ICP in the future pregnancies of affected mothers, also reinforces its genetic influences 1. For this reason, all pregnant women should be asked about their family history regarding liver dysfunction during pregnancy. Seasonal variations of the disease have been attributed to dietary factors related with high maternal levels of copper and low levels of selenium and zinc 16. Recently our group from Chile has also shown an increased intestinal permeability in ICP patients during and after pregnancy 17. This “leaky gut condition” may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxins and the enterohepatic circulation of cho-lestatic metabolites of sex hormones and bile salts. Figure 1 summarizes the main mechanisms involved in the multifac-torial pathogenesis of ICP. Clinical Presentation and Diagnosis ICP is clinically characterized by skin pruritus (often of the palms of the hands and soles of the feet), present-ing in the late second or early third trimester of pregnancy. Laboratory findings show increased fasting total serum bile salts (>10 μmol/L) and mild abnormalities of aminotransami-nases, with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) usually around 2-10 times the upper limit of normal 1-3. The traditional markers of cholestasis are difficult to interpret due to physiolog-ic elevations in alkaline phosphatase secondary to pregnancy. Gamma-glutamyl transferase (GGT) is usually normal (85-90% cases). In only 10- 20% of cases, conjugated mild hyper-bilirubinemia may be found, and in some severe cases jaundice. Imaging with ultrasound may be useful in excluding other causes of pruritus and jaundice, including cholelithiasis and biliary tract disease. The diagnosis of ICP is based on clinical history, physi-cal examination, and laboratory find-ings, but it may need the exclusion of other causes. All these abnormalities disappear in the following few days after delivery. The serum bile acid level is consid-ered the most sensitive and specific marker for the diagnosis of ICP (fast-ing serum bile acid concentrations greater than 10 μmol/L). Higher bile acid levels (>40 μmol/L) have been found recently to be associated with a significant higher rate of fetal com-plications 18. A higher level of bile acids may increase the sensitivity and expression of oxytocin receptors in the human myometrium inducing pre-term labor as a complication of ICP. Maternal and Fetal Prognosis ICP has no significant consequences for the mother; but in contrast, it is associated with an increased risk of fetal distress 1-3. Potential complica-tions associated with ICP include an increased risk of preterm delivery, meconium-stained amniotic fluid, and fetal distress, which may result in perinatal mortality (stillbirth). Older studies reported a perinatal mortality as high as 5-10%; however, with cur-rent active management this appears now to be <1-2% 3. Glantz et al. 18 described outcomes in 693 Swedish ICP patients, showing that perinatal mortality rates were slightly increased, but stillbirth was limited only to severe ICP patients characterized by total bile acid levels ≥ 40 μmol/L. Se-rum total bile acid levels >40 umol/L have been associated with increased risk of meconium staining, low Apgar scores, and preterm delivery, and in cases with bile acid levels of more than 100 umol/L it was associated with an increased risk of stillbirth 19. Author Year Country Pregnancies with ICP Spontaneous premature birth Fetal distress Stillbirth (perinatal death) Meconium-stained amniotic fluid Castaño G, et al 2006 Argentina 41 29% 2.4% 0% 9.7% Rioseco A, et al 1994 Chile 320 12.1% 2% 1.8% 25% Wang XD, et al 2006 China 1,210 24% 7.1% 2.25% 23.2% Alsulyman O, 1996 USA 79 14% 7.6% 2.5% 44.3% et al. Heinonen S, et al 1999 Finland 91 14.3 7.7% 0% 15.2% Roncaglia L, et al 2002 Italy 206 27.2% 5.3% 0% 16% Glantz A, et al. 2004 Sweden 693 4.5% 7.1% 0.4% 24.8% Table 2. Spontaneous perinatal complication rate in patients with intrahepatic cholestasis of pregnancy. Adapted by permission from Zapata R, Gla-sinovic JC. Intrahepatic cholestasis of pregnancy. In Perez-Sanchez, Donoso E (Eds): Clinical Obstetrics. Chile, Mediterraneo limitada, 2011, p 925. 11 Abreviations: ICP: intrahepatic cholestasis of pregnancy.
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