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Liver Disease in Pregnancy
Liver disease in pregnancy presents unique challenges to the clinician and requires careful and timely assessment. In addition to unique changes in the clinical course of chronic liver diseases (e.g., hepatitis B) which may occur during the course of pregnancy and at the time of delivery, a series of liver conditions unique to pregnancy have been described, including hyperemesis gravidarum, intrahepatic cholestasis of pregnancy (ICP), HELLP syndrome, and acute fatty liver of pregnancy (AFLP).
Hyperemesis gravidarum is characterized by severe nausea and vomiting during the first trimester of pregnancy. Its incidence is 0.35% to 0.8% of pregnancies, is rare to observe after 20 weeks of gestation, and may occasionally be accompanied by hyperthyroidism of uncertain etiology. In severe cases, hospitalization for intravenous hydration and antiemetic therapy may be required, and as many as 50% of patients may have abnormal results on liver function tests, which rarely reach levels greater than 1000 IU/L. Alternative etiologies such as viral hepatitis, gastric outlet obstruction, and gastroenteritis should be excluded. Treatment is limited to supportive care including hydration and antiemetics, including promethazine, ondansetron, and droperidol.
Intrahepatic Cholestasis of Pregnancy
ICP is an uncommon disorder of unknown etiology that typically develops during the second trimester and is associated with premature delivery and fetal death. The prevalence is reported to be 0.7% (United States) to 6.5% (Chile). The pathogenesis is unknown but believed to be related to genetic and hormonal factors, and patients with ICP appear to be more sensitive to the cholestatic effects of estrogen. The predominant clinical symptoms include severe pruritus and jaundice. The pruritus typically involves the palms and soles but may additionally affect the trunk and extremities. Jaundice often develops 1 to 4 weeks after the onset of pruritus in 20% to 60% of patients. Serum liver enzymes are commonly elevated and suggest either a hepatocellular, cholestatic, or mixed pattern of liver injury. Serum bile acid levels are also elevated and represent a more specific finding which signals the presence of ICP. Liver biopsy reveals bland cholestasis with bile plugs predominantly in zone 3 (central vein region) and intact portal tracts. However, liver biopsy is generally not needed for diagnosis.
The management of ICP is guided by the clinical symptoms. Early delivery at 36 weeks of gestation has been advocated for severe cases (if fetal lungs are mature) or alternatively 38 weeks for less severe cases. Cholestyramine (with vitamin K supplementation) can be used but may exacerbate fat malabsorption; ursodeoxycholic acid (UDCA) therapy represents an alternative therapeutic option. Clinical and biochemical abnormalities usually resolve a few weeks after delivery. Patients are at risk for recurrence with subsequent pregnancies or with oral contraceptive use.
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