Clinical practice guidelines of the Team of Experts of the Polish Gynecological Society: management of the intrahepatic cholestasis of pregnancy

Abstract

Intrahepatic Cholestasis of Pregnancy (ICP) constitutes the most common, reversible liver disease closely connected with pregnancy and spontaneously resolving in puerperium. ICP usually reoccurs in consecutive pregnancies (45-90%), often in a more intensified form. Many compounds (hormones, cytokines, medicines, endotoxins) can impair transport in the hepatocyte, disturb the intracellular transport and increase the permeability of the intercellular connections. As a result, the elements of bile may appear in the peripheral blood. Gestational cholestasis constitutes a classic example of intrahepatic cholestasis. The etiology of ICP is multifactorial with hormonal, genetic and environmental factors participating in the process. The diagnosis is based on the presence of pruritus, elevated values of bile acids in the blood serum and of aminotransferases (aspartic, aminopropionic and γ-glutamylotranspeptydase (AspAt, AlAt, GGTP)), as well as spontaneous remission in the second or third week after childbirth, of lack of other illnesses causing pruritus and icterus. Clinical and biochemical symptoms of ICP include: pruritus without skin rash (usually after 30 weeks of gestation), mild icterus, steatorrhea etc. Abnormalities in the laboratory tests of the LFT (liver function tests) encompass: an increase in the serum concentration of fatty acids (BA) which can be the first and only laboratory abnormality. Concentrations surpassing 10μmol/l are considered to be abnormal. Concentration of BA higher than 40 μmol/l allows to recognize a case of severe ICP, connected with the risk of premature delivery, presence of the meconium liquor, surgical means of delivery and low APGAR score of the newborn (<7 pt). In about 80% of pregnant women with ICP, the BA concentration ranges between 10-40 μmol/l, but perinatal results are comparable with uncomplicated pregnancies. Some authors are of the opinion that abnormal AlAt value is the most sensitive test, other authors consider the abnormal values of alkaline phosphatase and bilirubin to be the most pathognomonic factors. Other abnormal tests include: higher activity of α-hydroxybutyric dehydrogenase correlated with an increase of the alkaline phosphatase and bilirubin; mild metabolic acidosis; dyslipidemia with elevated concentrations of the total lipids, total cholesterol and free LDL cholesterol and apolipoprotein; abnormal glucose tolerance test. ICP constitutes a medical problem that carries a considerable risk for the fetus, resulting from an increased flow of bile acids to the fetal blood circulation (elevated level in the amniotic fluid, in the umbilical blood serum and meconium). The risk of adverse effects for the fetus correlates with the rise of BA concentration in maternal blood  serum. Cholestasis increases the risk of premature labor, presence of meconium in the amniotic fluid, fetal bradycardia, intrauterine asphyxia and stillbirth, particularly when the concentration of serum bile acids on an empty stomach is above 40 μmol/l. However, maternal clinical signs and symptoms do not correlate with the fetal outcome. Aspiration of bile acids or their accumulation in the fetal blood circulation are responsible for the increased frequency of RDS appearing in ICP. The aim of the obstetric management of ICP is to reduce maternal symptoms and biochemical disorders and to minimize the risk of premature delivery, fetal distress and sudden death. ICP management should include: bed regime, light, low-fat diet, no stress, upper abdomen ultrasound examination, LFT tests and thrombotic tests once a week, monitoring of the fetal well-being with the available biophysical methods, pharmacotherapy and therapeutic termination of pregnancy in case of serious illness and/or the fetal distress. Ursodeoxycholic acid (UDCA) is the basis of the pharmacological treatment of pregnant women and currently constitutes the most promising treatment option of ICP. UDCA is administered orally in the dosage of 10-16 mg/kg/24, what in practice means 250-300 mg/2-3 times a day.