| Intrahepatic cholestasis of pregnancy (ICP), also called obstetric cholestasis, is a disorder characterized clinically by pruritus, icterus, or both, biochemical disturbances in liver enzymes. It was first reported by Ahlfeld in 1883 in a classic manuscript and was originally considered a benign condition of pregnancy. But later it was reported that ICP has been associated not only with poor fetal outcomes, including increased incidence of meconium-stained amniotic fluid, fetal intolerance of labor, spontaneous preterm labor, and unpredictable intrauterine fetal demise, but also with acute fatty liver of pregnancy.The pathogenesis of the disease is poorly understood. Liver biopsy shows cholestasis with intracellular bile pigment and canalicular bile plugging without necrosis. Bile acids are cleared incompletely by liver and accumulated in plasma of patients. Serum concentration of total bile acids may be elevated 10- to 100-fold. The retention of conjugated pigment results in hypefbilirubinemia, elevated serum transaminase activities. The cause is unknown, and it was assumed to be stimulated in susceptible persons by high estrogen concentrations. However, Leslie and colleagues recently reported that maternal plasma estrogens are decreased in affected women compared with matched controls. Reyes and Siovall have proposed that there is a defect in secretion of sulfated progesterone metabolites. There is evidence that ICP is related to the many gene mutations that control hepatocellular-transport systems. Because of these genetic influences the incidence of ICP varies. It is common in Chile and Sweden, about 4%-12%; it is rare in USA, only 0.1%-0.2%.Clinical presentations of most ICP patients develop pruritus in second and late pregnancy although the syndrome occasionally occurs as early as 13 weeks.It is quite troublesome to management the pruritus associated with cholestasis caused by elevated serum bile salts. Orally administered antihistamines such as cholestyramine may or may not provide some relieve even worsen the already impaired absorption of fat-soluble vitamins, which result in spontaneous intracranial hemorrhage fetus whose mother developed hypothrombinemia with cholestyramine therapy. Other retrospective observations showed that ursodeoxy-cholic acid (UDCA), a naturally occurring hydrophilic bile acid that modifies the bile acid pool composition by replaceing lithocolic acid, which is more cytotoxic to the liver cell membranes, could relieve pruritus and low serum hepatic enzyme levels in ICP patients through decreasing the intestinal absorption of cholic and chenodeoxycholic acid. But in JCP patients the excretion of bile acids is diminished, intestinal absorption of cholic and chenoldeoxycholic acid is very little. So it takes long time, above 20 days, to improve symptoms. Some stillbirths occurred before effects.S-adenyl-methionine (SAMe) has been shown to decrease the negative effects of ethinyl estradiol on bile flow and increase sulphates necessary for detoxification of bile acids. But it was not effective to relieve pruritus and to decline bile acids and aminotransferase till 20-days treatment course with 800mg of parenteral SAMe. However, Ribalta et al. administered 800mg of SAMe for a 20-days period without significant improvement of ICP.The goal of phamacologic treatment is to improve maternal symptoms, to recover the biochemical markers and to protect fetus from jeopardizing. Medication with no or minimal maternal/fetal side effect, which decreases the production of bile acid, is preferred. Developing effective treatment in ICP is needed further research.During clinical practice, we have found that most ICP patients were accompanied with hypercoagulant state, such as high viscosity, hyperfibrinogenemia, high hematocrit levels, and hyperltpidemia. While regularly treating with SAMe for ICP, we used low dose heparin for anticoagulant to prevent against embolism. Surprisingly, we found that the ICP patients recovered quickly after addition of heparin.Therefore, thre... |
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