• Intrahepatic Cholestasis of Pregnancy his condition has been called recurrent jaundice of pregnancy, cholestatic hepatosis, and icterus gravidarum and is characterized by pruritus, icterus, or both. It may be more common in multifetal pregnancy, and there is a significant genetic influence (Lausman, 2008; Webb, 2014). Because of this, its incidence varies by population. For example, cholestasis is infrequent in North America, with an overall incidence approximating 1 case in 500 to 1000 pregnancies. But, its rate nears 5.6 percent among Latina women in Los Angeles (Lee, 2006). Historically, indigenous women from Chile and Bolivia also have a relatively high incidence. For unknown reasons, this incidence has declined since the 1970s and is now less than 2 percent (Reyes, 2016). In other countries, for example Sweden, China, and Israel, the incidence varies from 0.25 to 1.5 percent (Glantz, 2004; Luo, 2015; Sheiner, 2006).
The cause of obstetrical cholestasis is unclear, but changes in various sex steroid levels are implicated. However, current research focuses on the numerous mutations in the many genes that control hepatocellular transport systems. Examples include mutations of the ABCB4 gene, which encodes multidrug resistance protein 3 (vlDR3) associated with progressive amilial intrahepatic cholestasis, and errors of the ABCBll gene, which encodes a bile-salt export pump (Anzivino, 2013; Dixon, 2014). Other potential gene products are the farnesoid X receptor and transporting ATPase encoded by A TP8Bl (Abu-Hayyeh, 2016; Davit-Spraul, 2012). Some drugs that similarly decrease canalicular transport of bile acids aggravate the disorder. We have encountered impressive cholestatic jaundice in gravidas taking azathioprine following renal transplantation.
Whatever the inciting cause(s), bile acids are cleared incompletely and accumulate in plasma. Hyperbilirubinemia results from retention of conjugated pigment, but total plasma concentrations rarely exceed 4 to 5 mg/ dL. Alkaline phosphatase levels are usually elevated even more than in normal pregnancy. Serum transaminase levels are normal to moderately elevated but seldom exceed 250 U/L (see Table 55-1). Liver biopsy shows mild cholestasis with bile plugs in the hepatocytes and canaliculi of the centrilobular regions, but without inflammation or necrosis. These changes disappear after delivery but often recur in subsequent pregnancies or with estrogencontaining contraceptives.
Pruritus develops in late pregnancy, although it occasionally manifests earlier. Constitutional symptoms are absent, and generalized pruritus shows predilection for the soles. Skin changes are limited to excoriations from scratching. Biochemical tests may be abnormal at presentation, but pruritus may precede laboratory indings by several weeks. Approximately 10 percent of women have jaundice.
With normal liver enzymes, the diferential diagnosis of pruritus includes other skin disorders (Table 62-1, p. 1185). Findings are unlikely to stem from preeclamptic liver disease if blood pressure elevation or proteinuria is absent. Sonography may be warranted to exclude cholelithiasis and biliary obstruction. Moreover, acute viral hepatitis is an unlikely diagnosis because of the usually low serum transaminase levels seen with cholestasis. Conversely, chronic hepatitis C is associated with a significantly increased risk of cholestasis, which may be as high as 20-fold among women who test positively for hepatitis C RNA (Marschall, 2013).