Intrahepatic Cholestasis in Pregnancy: Review of the Literature

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered.

Role of serum organic solute transporter alpha/beta and sodium taurocholate cotransporting polypeptide in intrahepatic cholestasis of pregnancy

“…Intrahepatic cholestasis of pregnancy has a complex and multifaceted etiology, involving complex interactions between genetic features, endocrine and metabolic disturbances, and environmental factors [4]. Altered secretion and transport of bile acids and other biliary lipids play an important role on the etiology of ICP [9].…”

“…The incidence of ICP is estimated to range between 1% and 4%, but varies greatly depending on environmental factors, ethnic origin and genetic predisposition [3]. The etiopathogenesis of the disease is not fully understood, but is probably multifactorial with genetic, environmental, dietary and hormonal backgrounds that also effect its severity [4]. The impairment of the transport, excretion and function of bile acids may be associated with the development of ICP.…”

Perinatal Outcomes among Women with Cholestasis of Pregnancy

“…3 Two such mutated genes are MDR3 and ABCB4. 7,8 Secondary effects of cholestasis as observed in animal studies, show estradiol 17 β-d-glucuronide to be cholestatic. 9 In addition, substantial amounts of sulfated progesterone metabolites in the urine of pregnant women are additionally conjugated with N-acetyl glucosamine and the formation of such metabolites is selective for β-hydroxy bile acids, such as, ursodeoxycholic acid (UDCA) which are a front-line treatment for ICP.…”

“…Commonly used biochemical markers like alanine aminotransferases (ALT) and aspartate aminotransferase (AST) which are also commonly raised in ICP could benefit in early diagnosis of ICP. 7 Hence, accurate and rapid diagnosis and quality treatment help prevent adverse perinatal outcomes. 10 Various therapies have been administered, for ICP like antihistamines, cholestyramine resin, UDCA, etc.…”

Ursodeoxycholic acid improves pregnancy outcome in patients with intrahepatic cholestasis during pregnancy

“…[ 6 ] The incidence of ICP varies greatly among different ethnic groups and regions. In Poland, the incidence is 1% to 4%, whereas in Europe, North America, and Australia, the incidence is about 1% to 2%, [ 7 ] and in China, the incidence is 2.3% to 6.0%. [ 8 ]…”