INTRODUCTION — When hepatobiliary disease presents during pregnancy, the etiology may be unrelated to pregnancy (eg, acute viral hepatitis) or specific to pregnancy (eg, intrahepatic cholestasis of pregnancy [ICP]). In addition, physiologic changes of pregnancy may increase the risk or worsen the severity of some hepatobiliary diseases that also occur in nonpregnant women (eg, cholelithiasis).
This topic is an overview of hepatobiliary diseases that may present during but are not specific to pregnancy.
The approach to evaluating a pregnant patient who presents with signs or symptoms of hepatobiliary disease (eg, jaundice) is discussed separately. (See "Approach to evaluating pregnant patients with elevated liver biochemical and function tests".)
Issues related to pregnancy and contraception in women with chronic liver disease are discussed separately. (See "Pregnancy in women with pre-existing chronic liver disease" and "Hepatitis B and pregnancy".)
Liver diseases that are specific to pregnancy are discussed separately:
●ICP (see "Intrahepatic cholestasis of pregnancy")
●HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) (see "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)")
●Hyperemesis gravidarum (see "Nausea and vomiting of pregnancy: Clinical findings and evaluation" and "Nausea and vomiting of pregnancy: Treatment and outcome")
●Acute fatty liver of pregnancy (see "Acute fatty liver of pregnancy")
ACUTE VIRAL HEPATITIS — Acute viral hepatitis can complicate pregnancy. Although vaccination may prevent acute infection with hepatitis A virus (HAV) and hepatitis B virus (HBV), a large pool of unvaccinated, nonimmune women worldwide remains at risk for developing these diseases during pregnancy. Hepatitis A and B vaccinations are regarded as safe to administer to pregnant women with or without increased risk for exposure to these viruses [1,2].
Hepatitis A virus — HAV infection is a common cause of acute viral hepatitis in the general population; however, it is rarely reported in pregnancy. The course of HAV infection during pregnancy is generally similar to that in nonpregnant patients, although maternal and fetal complications have been reported . The disease tends to be more severe with increasing age in all patients, and severe illness during the third trimester may be associated with an increased risk for premature labor . Treatment for pregnant women with acute HAV infection is supportive (eg, rest, maintaining oral intake), and the infection is usually self-limited. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Treatment'.)
Gestational complications may occur with acute HAV infection. In a review of almost 80,000 pregnancies, 13 cases of acute HAV during the second and third trimester were detected . Of these, 69 percent developed gestational complications including premature contractions, placental separation, premature rupture of the membranes, and vaginal bleeding . Eight patients developed preterm labor at a median of 34 weeks gestational age. Despite these occurrences, all children had favorable outcomes. In another study including over 16,000 deliveries, 12 acute HAV infections were identified, and complications included two cases of cholestatic hepatitis and one case of preterm labor . Perinatal and intrauterine  transmission of the virus is rare [3,5,7].
Hepatitis B virus — Acute HBV infection during pregnancy has not been associated with increased maternal or fetal mortality or teratogenicity . If acute HBV infection occurs in pregnancy, serial monitoring should be performed throughout pregnancy to assess liver function and for loss of hepatitis B surface antigen (HBsAg). Newborns should receive hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccination at birth. For HBsAg-positive pregnant patients, an HBV DNA level should be checked at approximately 28 weeks of gestation to determine if antiviral therapy should be initiated to decrease the risk of perinatal transmission. Management of acute and chronic HBV infection during pregnancy is discussed in more detail separately. (See "Hepatitis B and pregnancy".)
Hepatitis C virus — Hepatitis C virus (HCV) infection rates have increased substantially over the past decade, and routine, one-time HCV screening for nearly all adults is advised [9,10]. (See "Screening and diagnosis of chronic hepatitis C virus infection".)
The Centers for Disease Control and Prevention (CDC) has recommended HCV screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1 percent . The approach to screening asymptomatic pregnant women for HCV and other infections is discussed separately. (See "Prenatal care: Initial assessment", section on 'Infection'.)
Acute HCV infection during pregnancy is rarely recognized, likely due to the minimally symptomatic presentation. When acute HCV infection is reported, jaundice is a common presenting symptom . Data on the impact of acute HCV infection (eg, risk of maternal to child transmission, adverse pregnancy outcomes) are limited, and clinical features, diagnosis, and vertical transmission of HCV infection are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults" and "Vertical transmission of hepatitis C virus".)
Treatment of HCV during pregnancy is not routinely recommended . (See "Overview of the management of chronic hepatitis C virus infection".)
Hepatitis E virus — Hepatitis E virus (HEV) infection occurs both in epidemics and sporadically in many parts of the developing world . HEV genotypes differ in their prevalence by geographic region and in their route of transmission. For example, genotypes 3 and 4 are more prevalent in developed countries and have been associated with mildly symptomatic disease and zoonotic transmission (eg, consumption of undercooked pork and wild boar) . HEV genotypes 1 and 2 are transmitted via the fecal-oral route, and infection during pregnancy has been associated with risk of acute liver failure, especially in the third trimester. Case fatality rate of up to 20 percent has been reported [15,16]. Pregnant women with jaundice and acute viral hepatitis caused by HEV infection appear to have worse obstetric and fetal outcomes compared with pregnant women with jaundice and acute viral hepatitis due to other causes . Because of this risk, pregnant women should carefully consider the risk of travel to endemic areas.
Acute liver failure due to HEV may resemble liver failure from other causes such as acute fatty liver of pregnancy; hepatic infarction in the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP); or herpes simplex hepatitis . HEV infection should be considered in all pregnant women who develop acute hepatitis, especially in endemic areas.
Testing for HEV antibodies or the presence of HEV RNA establishes the diagnosis. Serologic and nucleic acid tests are commercially available but not approved by the US Food and Drug Administration (FDA). Treatment of HEV infection during pregnancy consists of supportive care. Ribavirin and interferon have been used for treating HEV infection in nonpregnant patients, but these agents are contraindicated during pregnancy. The epidemiology, clinical features, diagnosis, and treatment of HEV infection are discussed separately. (See "Hepatitis E virus infection".)
Herpes simplex hepatitis — Hepatitis due to primary systemic infection with herpes simplex virus (HSV) may be severe when occurring during pregnancy, and cases of fulminant herpetic hepatitis have been reported . Both maternal and neonatal mortality rates are high. Affected patients may have a prodrome of fever and upper respiratory tract symptoms. Despite marked abnormalities in serum aminotransferases and the prothrombin time, patients are usually anicteric at presentation. HSV hepatitis should be considered in all patients presenting with fever and anicteric hepatitis. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Hepatitis'.)
A vesicular eruption is uncommon but, if present, suggests the diagnosis. Culture of the vesicular fluid, serologic testing, and liver histology help to distinguish herpetic hepatitis from other severe liver disorders associated with pregnancy, such as acute fatty liver of pregnancy and preeclamptic liver disease. In contrast with those diseases, delivery is usually unnecessary and empiric therapy with acyclovir is recommended [21-23]. (See "Treatment and prevention of herpes simplex virus type 1 in immunocompetent adolescents and adults".)
Other viruses — Cytomegalovirus, Epstein-Barr virus, and adenoviruses can cause hepatitis in association with systemic infection, which are usually self-limited, requiring only supportive care. However, transmission to the fetus can occur [24,25]. (See "Cytomegalovirus infection in pregnancy".)
BILIARY TRACT DISEASE
Gallstones — Gallstones are more common during pregnancy due to decreased gallbladder motility and increased cholesterol saturation of bile. Gallstone disease during pregnancy has been associated with increased risk of preterm birth and maternal morbidity, and issues related to gallstones in pregnant women are discussed in detail separately. (See "Gallstone diseases in pregnancy".)
Acute pancreatitis — Acute pancreatitis is a rare complication of pregnancy [26-29]. Approximately two-thirds of cases are biliary in origin [28,29]; such cases are associated with better outcomes than nonbiliary causes . (See "Gallstone diseases in pregnancy", section on 'Gallstone pancreatitis'.)
In selected patients, diagnoses other than gallstone pancreatitis should be considered, such as alcohol and hypertriglyceridemia. In rare cases, pancreatitis during pregnancy is associated with acute fatty liver of pregnancy, preeclampsia, hyperemesis gravidarum, and familial hypertriglyceridemia, which may be exacerbated by the physiologic hypertriglyceridemia of pregnancy [30,31]. (See "Hypertriglyceridemia-induced acute pancreatitis".)
Choledochal cyst — A choledochal cyst can present during pregnancy. Changes in biliary motility associated with pregnancy may lead to the development of symptoms in previously asymptomatic patients who have a congenital choledochal cyst. Symptomatic patients present with abdominal pain, right upper quadrant mass, and jaundice . Surgical intervention is typically deferred until after delivery . Spontaneous rupture of a choledochal cyst is a rare complication . (See "Biliary cysts".)
Budd-Chiari syndrome — Nearly 20 percent of cases of the Budd-Chiari syndrome (hepatic venous outflow obstruction) occur in women who have been on oral contraceptives, are pregnant, or have delivered a child within the previous two months . It is presumed that the hypercoagulable state in these women is responsible for this association. (See "Combined estrogen-progestin contraception: Side effects and health concerns" and "Etiology of the Budd-Chiari syndrome", section on 'Oral contraceptives and pregnancy'.)
In addition, pregnancy may exacerbate other hypercoagulable states that predispose to the Budd-Chiari syndrome, such as antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, factor V Leiden, and protein S deficiency [36,37]. Thus, an underlying cause of hypercoagulability other than pregnancy should be sought in all patients. (See "Etiology of the Budd-Chiari syndrome".).
Management of Budd-Chiari syndrome presenting in pregnancy is similar to the nonpregnant population with the exception that vitamin K antagonists for anticoagulation are contraindicated in pregnancy (see "Budd-Chiari syndrome: Management"). Reports have documented excellent survival and delivery with supportive care and anticoagulation . Liver transplantation has been used as a lifesaving measure [39,40]. Recurrence during a subsequent pregnancy has been reported in a patient whose anticoagulants were discontinued .
Portal vein thrombosis — Portal vein thrombosis is rare in pregnancy . The prothrombotic state of pregnancy is a risk factor for developing this condition especially in women with cirrhosis. Portal vein thrombosis can increase the risk of developing portal hypertension and its complications (eg, esophageal varices). Management of portal vein thrombosis is similar to the nonpregnant population with the exception that vitamin K antagonists for anticoagulation are contraindicated in pregnancy. (See "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)
DRUG-INDUCED LIVER INJURY — Because of concern about teratogenicity in the fetus, pregnant women generally take fewer medications than nonpregnant women. Pregnancy has not been associated with an increased susceptibility to drug-induced liver injury (DILI). However, hepatotoxicity due to drugs may occur during pregnancy and should be considered in pregnant patients with abnormal liver biochemical tests who have been taking prescription or nonprescription medications, including herbal compounds. (See "Hepatotoxicity due to herbal medications and dietary supplements" and "Drug-induced liver injury".)
SEPSIS-ASSOCIATED CHOLESTASIS — Sepsis, particularly originating from the urinary tract, can lead to cholestasis . As a result, patients who develop cholestasis during pregnancy are evaluated for urinary tract infections, and this is discussed separately. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)
SUMMARY AND RECOMMENDATIONS
●Background – When hepatobiliary disease presents during pregnancy, the etiology may be unrelated to pregnancy (eg, acute viral hepatitis) or specific to pregnancy (eg, intrahepatic cholestasis of pregnancy [ICP]). In addition, physiologic changes of pregnancy may increase the risk or worsen the severity of some hepatobiliary diseases that also occur in nonpregnant women (eg, cholelithiasis).
Issues related to pregnancy and contraception in patients with chronic liver disease are discussed separately. (See "Pregnancy in women with pre-existing chronic liver disease".)
●Acute viral hepatitis – Acute viral hepatitis can complicate pregnancy. The course of hepatitis A, B, and C virus (HAV, HBV, HCV) infection is similar to that of nonpregnant patients. By contrast, hepatitis E virus (HEV) infection may be more severe during pregnancy. (See 'Acute viral hepatitis' above and "Hepatitis B and pregnancy".)
●Gallstones – Pregnancy is associated with an increased risk for gallstones due to decreased gallbladder motility and increased cholesterol saturation of bile. (See 'Gallstones' above and "Gallstone diseases in pregnancy".)
●Budd-Chiari syndrome – Nearly 20 percent of cases of Budd-Chiari syndrome (hepatic venous outflow obstruction) occur in patients who have been on oral contraceptives, are pregnant, or have delivered a child within the previous two months. It is presumed that the hypercoagulable state in such patients is responsible for this association. (See 'Budd-Chiari syndrome' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Yannick Bacq, MD, and Dr. Tram T Tran, MD for their past contributions as authors to prior versions of this topic review.
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