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Hepatic Disorders in Pregnancy

by Lara A. Friel, MD, PhD

Hepatic disorders in pregnancy may be

  • Unique to pregnancy

  • Preexisting

  • Coincident with pregnancy and possibly exacerbated by pregnancy

Jaundice

Jaundice (see Jaundice) may result from nonobstetric or obstetric conditions.

Nonobstetric causes include

  • Acute viral hepatitis (most common)

  • Drugs

  • Acute cholecystitis

  • Biliary obstruction by gallstones

Gallstones appear to be more common during pregnancy, probably because bile lithogenicity is increased and gallbladder contractility is impaired.

Obstetric causes include

  • Hyperemesis gravidarum (usually causing mild jaundice)

  • Septic abortion

Both cause hepatocellular injury and hemolysis.

Acute viral hepatitis

The most common cause of jaundice during pregnancy is acute viral hepatitis. Pregnancy does not affect the course of most types of viral hepatitis (A, B, C, D); however, hepatitis E may be more severe during pregnancy.

Acute viral hepatitis may predispose to preterm delivery but does not appear to be teratogenic.

Hepatitis B virus may be transmitted to the neonate immediately after delivery or, less often, to the fetus transplacentally. Transmission is particularly likely if women are e-antigen–positive and are chronic carriers of hepatitis B surface antigen (HBsAg) or if they contract hepatitis during the 3rd trimester. Affected neonates are more likely to develop subclinical hepatic dysfunction and become carriers than to develop clinical hepatitis. All pregnant women are tested for HBsAg to determine whether precautions against vertical transmission are needed (for prenatal prophylaxis with immune globulin and vaccination for neonates exposed to hepatitis B virus—see Neonatal Hepatitis B Virus Infection : Prevention).

Chronic hepatitis

Chronic hepatitis, especially with cirrhosis, impairs fertility. When pregnancy occurs, risk of spontaneous abortion and prematurity is increased, but risk of maternal mortality is not.

Despite standard immunoprophylaxis, many neonates of women with a high viral load are infected with hepatitis B virus. Data suggest that antiviral drugs given during the 3rd trimester may prevent immunoprophylaxis failure. Fetal exposure should be minimized by using antiviral drugs only when women have advanced hepatitis or hepatic decompensation is a risk. Lamivudine, telbivudine, or tenofovir are most commonly used.

Corticosteroids given to treat chronic autoimmune hepatitis before pregnancy can be continued during pregnancy because fetal risks due to corticosteroids have not been proved to exceed those due to maternal chronic hepatitis. Azathioprine and other immunosuppressants, despite fetal risks, are sometimes indicated for severe disease.

Intrahepatic cholestasis (pruritus) of pregnancy

This relatively common disorder apparently results from idiosyncratic exaggeration of normal bile stasis due to hormonal changes. Incidence varies based on ethnicity and is highest in Bolivia and Chile.

Consequences include increased risk of fetal prematurity, stillbirth, and respiratory distress syndrome.

Intense pruritus, the earliest symptom, develops during the 2nd or 3rd trimester; dark urine and jaundice sometimes follow. Acute pain and systemic symptoms are absent. The disorder usually resolves after delivery but tends to recur with each pregnancy or with use of oral contraceptives.

The disorder is suspected based on symptoms. The most sensitive and specific laboratory finding is a fasting total serum bile acid level of > 10 mmol/L. This finding may be the only biochemical abnormality present. Fetal demise is more likely when the fasting total bile acid level is > 40 mmol/L.

Ursodeoxycholic acid (UDCA) 5 mg/kg po bid or tid (or up to 7.5 mg/kg bid) is the drug of choice. It helps lessen the severity of symptoms and normalize biochemical markers of liver function; however, it does not decrease the incidence of fetal complications.

Fatty liver of pregnancy

This rare, poorly understood disorder occurs near term, sometimes with preeclampsia. Patients may have an inherited defect in mitochondrial fatty acid β-oxidation (which provides energy for skeletal and cardiac muscle); risk of fatty liver of pregnancy is 20 times higher in women with a mutation affecting long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), particularly the G1528C mutation on one or both alleles (autosomally inherited).

Symptoms include acute nausea and vomiting, abdominal discomfort, and jaundice, followed in severe cases by rapidly progressive hepatocellular failure. Maternal and fetal mortality rates are high in severe cases.

A seemingly identical disorder may develop at any stage of pregnancy if high doses of tetracyclines are given IV.

Clinical and laboratory findings resemble those of fulminant viral hepatitis except that aminotransferase levels may be < 500 units/L and hyperuricemia may be present.

Diagnosis is based on clinical criteria, liver function tests, hepatitis serologic tests, and liver biopsy. Biopsy shows diffuse small droplets of fat in hepatocytes, usually with minimal apparent necrosis, but in some cases, findings are indistinguishable from viral hepatitis.

Affected women and their infants should be tested for known genetic variants of LCHAD.

Depending on gestational age, prompt delivery or termination of pregnancy is usually advised, although whether either alters maternal outcome is unclear. Survivors recover completely and have no recurrences.

Preeclampsia

Severe preeclampsia (see Preeclampsia and Eclampsia) can cause liver problems with hepatic fibrin deposition, necrosis, and hemorrhage that can result in abdominal pain, nausea, vomiting, and mild jaundice.

Subcapsular hematoma with intra-abdominal hemorrhage occasionally occurs, most often in women with preeclampsia that progresses to the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). Rarely, the hematoma causes the liver to rupture spontaneously; rupture is life threatening, and pathogenesis is unknown.

Chronic hepatic disorders

Pregnancy may temporarily worsen cholestasis in primary biliary cirrhosis and other chronic cholestatic disorders, and the increased plasma volume during the 3rd trimester slightly increases risk of variceal hemorrhage in women with cirrhosis. However, pregnancy usually does not harm women with a chronic hepatic disorder.

Cesarean delivery is reserved for the usual obstetric indications.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • VIREAD
  • EPIVIR
  • IMURAN
  • TYZEKA

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