The presentation of viral hepatitides ranges from mild, nonclinical illness to fulminant hepatic necrosis. Viral hepatitis is the most common cause of jaundice and the most frequent reason for gastroenterology consultation during pregnancy. Six types—hepatitis A, B, C, D, E, and G—have been identified and are associated with specific viruses. Types A, B, and C are the most common. Infrequently, hepatitis can also be caused by herpes simplex virus (HSV), yellow fever virus, rubella virus, Epstein-Barr virus, or cytomegalovirus.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) are typically spread by oral ingestion of food or water contaminated with feces from infected individuals. Although endemic in other countries, the current all-time low incidence of HAV of 0.4 per 100,000 in the United States is attributed to good sanitation. Despite its prevalence, it has been infrequently reported among pregnant women. The incidence of HAV infection has also been reduced by vaccination for preexposure prophylaxis; immune globulin is available for postexposure prophylaxis to prevent or attenuate infection. Clinically, a preicteric phase typically occurs with nonspecific viral symptoms, followed by an icteric phase with jaundice and acholic stools. Acute treatment is supportive. Increased risk for preterm labor, premature rupture of membranes, and placental abruption have been associated with HAV during pregnancy, and vertical transmission to the fetus may occur. Chronic HAV infection does not occur, but a prolonged or relapsing course occurs in up to 20% of patients, and an acute fulminant course occurs in less than 1% of patients.

HEV infection may be largely asymptomatic. In symptomatic patients, the disease is usually self-limited. Pregnant women and patients already infected with another hepatitis virus, however, have more severe presentations. A mortality rate of up to 20% has been reported in pregnant women with acute HEV infection, a consequence of fulminant hepatic failure, eclampsia, and hemorrhagic complications. Pregnancy complications such as premature rupture of membranes, fetal growth restriction, placenta previa, retained placenta, and preterm delivery are also more common. Chronic HEV infection may occur in immunosuppressed patients, and vertical transmission can occur. Pegylated interferon and/or ribavirin treatment for chronic HEV infection has shown moderate success. An HEV vaccine was approved for use in China in 2012 but is not yet available elsewhere.

Hepatitis B virus (HBV) and hepatitis D virus (HDV) are usually transmitted via percutaneous or permucosal exposure to infected body fluids. In high-prevalence areas, HBV infection is most commonly acquired perinatally or in early childhood. In low-prevalence areas, infection is primarily acquired in adulthood through sexual contact or intravenous drug abuse. Implementation of widespread vaccination and safety precautions in healthcare settings has reduced the incidence. Postexposure prophylaxis with HBV vaccination alone or a combination of vaccination with hepatitis B immune globulin (HBIG) is highly effective in preventing HBV transmission in adults as well as in infants of HBV-infected mothers and may prevent perinatal transmission. The majority of acute infections are asymptomatic, with only 30% of adults developing typical symptoms of hepatitis, and less than 0.5% developing fulminant hepatitis. Most cases can be managed with supportive treatment, although nucleoside analog therapy may improve prognosis in severe cases. Chronic HBV develops in less than 5% of adults but in more than 20% of children, and exacerbations of chronic HBV may occur postpartum. The 5-year cumulative incidence of cirrhosis in chronic HBV may be as high as 20%, and once cirrhosis has developed the annual risk for hepatocellular carcinoma may be as high as 5%. Treatment of chronic HBV aims at clearance of virus to prevent the development of cirrhosis and cancer. Vertical transmission to the fetus from hepatitis Be antigen-positive mothers can be as high as 90% without attempts to prevent transmission. Vertical transmission is most likely to occur at delivery but can also occur in utero . For patients with active disease or high viral loads, oral antiviral therapies ( lamivudine , telbivudine , or tenofovir ) reduce transmission without apparent increased risk for adverse maternal or fetal outcomes, as does cesarean delivery. Interferon therapy has a finite course of treatment and an increased chance of viral clearance and reduces the risk for cirrhosis and liver cancer; however, it has more side effects and is contraindicated during pregnancy. Current recommendations are to administer HBV vaccination to all neonates and to administer HBIG to all offspring of infected mothers.

HDV is dependent on HBV coinfection to replicate. Acute coinfection with both viruses can be more severe than acute HBV infection alone and may result in acute liver failure. HDV superinfection in the setting of chronic HBV results in chronic HDV infection in most patients, and these patients have more rapid progression to cirrhosis.

Hepatitis C virus (HCV) transmission most commonly occurs from transfusion of infected blood products or injection of contaminated drugs (illicit or iatrogenic). Maternal-fetal and sexual transmission are less common routes of transmission; however, the rate of vertical transmission is increasing in the United States as injection drug use increases in the context of the opioid crisis, so the prevalence of HCV in pregnancy has increased. Initial infection is generally asymptomatic, but up to 30% of patients develop acute hepatitis. In patients with acute HCV infection that has not cleared spontaneously within 12 weeks, treatment with pegylated interferon may be used to prevent chronic infection, with treatment success in up to 98% of patients. In most asymptomatic and untreated cases, infection persists for over 6 months and leads to chronic infection with progression to cirrhosis in up to 30% of patients within 30 years. Thus, HCV is the leading cause of chronic hepatitis, cirrhosis, and liver cancer (which develops in up to 3% of patients per year) and a primary indication for liver transplantation in the developed world. Depending on the severity of liver fibrosis, therapy may be warranted to prevent these complications. Combination treatment with pegylated interferon, ribavirin, and a protease inhibitor can result in a sustained virologic response in up to 80% of patients, but it is contraindicated during pregnancy. Various second-generation antiviral drugs have been introduced for single-agent or combination regimens to clear HCV infection, but there are insufficient data to endorse their use during pregnancy. Maternal HCV infection is associated with an increased rate of intrauterine fetal demise, preterm delivery, fetal growth restriction, gestational diabetes, antepartum and postpartum hemorrhage, and intrahepatic cholestasis of pregnancy secondary to HCV-induced changes in hepatocytes and biliary epithelial cells. Pregnant women with viremia have a mother-to-child transmission rate of about 5.8%, which increases to 10.8% if coinfection with human immunodeficiency virus (HIV) is present.

Hepatitis G virus (HGV) is transmitted parenterally, sexually, or vertically. In the United States, nearly 20% of all blood preparations are infected with HGV. Although there have been reports of acute, fulminant, and chronic hepatitis and hepatic fibrosis, HGV replicates predominantly in the hematopoietic system rather than in hepatocytes. Clinical significance is mostly for those coinfected with HCV or HIV or for individuals with hematologic cancers.

HSV hepatitis is a rare form of hepatitis in pregnancy; however, it is associated with a maternal mortality rate as high as 39%. The risk for disseminated HSV is high when the primary infection occurs during pregnancy. Signs and symptoms include fever, transaminitis, gastrointestinal, respiratory, neurologic, and urogenital manifestations, while only 18% present with a vesicular rash. Because diagnosis can be difficult, empiric treatment with acyclovir may be indicated when pregnant women present with fulminant hepatic failure of unknown origin, as this may improve outcomes and obviate the need for liver transplantation.

Cholelithiasis is present in up to 8% of pregnant women, although only 1.2% develop symptomatic disease. Patients may have right upper-quadrant pain, fever, and leukocytosis, and diagnosis is generally made by ultrasonography. Serious complications include cholangitis , pancreatitis , gangrenous cholecystitis , and perforation . Conservative treatment may be considered in mild cases and includes intravenous hydration, antibiotics, opioid analgesia, bowel rest, and possibly percutaneous cholecystostomy. Although a conservative approach does not seem to be associated with poorer fetal outcomes, treatment failure or disease recurrence during pregnancy is common, so therefore surgical treatment may ultimately be required. Both open and laparoscopic cholecystectomy (preferably in the second trimester) can be considered, though laparoscopic techniques offer maternal recovery advantages similar to those in the nonpregnant patient and may have slightly lower fetal complication rates. With either technique, the incidence of miscarriage or preterm labor/delivery is greater than 25%.

Liver abscess can develop from infection by various organisms including Entamoeba , Echinococcus , Clonorchis , and Ascaris . Direct inoculation during medical instrumentation or hematogenous spread from intravenous drug abuse or endocarditis can occur. Appendicitis, diverticulitis, or other intra-abdominal infections may spread to the liver. Fungal infections are also possible in immunocompromised patients. Management of liver abscess includes antimicrobials, percutaneous or open drainage, and surgical resection. The condition is rare during pregnancy, but treatment modalities are similar to those described for the nonpregnant patient.

Autoimmune hepatitis , primary biliary cirrhosis , and primary sclerosing cholangitis are conditions that may overlap and may also be associated with other extrahepatic autoimmune disorders. All may lead to end-stage liver disease, and treatment with corticosteroids, other immunosuppressants, and/or ursodeoxycholic acid is aimed at preventing this progression. For advanced and intractable disease, liver transplantation may be necessary. Pregnancy in autoimmune hepatitis is associated with a 33% incidence of disease flares (mostly postpartum), one-third of which result in maternal hepatic decompensation, liver transplantation, or death. Risks for hypertensive complications of pregnancy, gestational diabetes, preterm birth, and low birth weight are also increased. Immunosuppressive therapy during pregnancy is reportedly safe and effective for reducing disease flares. Continuation of immunosuppression with prednisone and azathioprine during pregnancy increases control of disease and decreases flares, which may lead to fulminant liver failure. Mycophenolate mofetil and tacrolimus are contraindicated in pregnancy.

Budd-Chiari syndrome involves thrombosis of the hepatic vein or suprahepatic inferior vena cava and may be associated with pregnancy (comprising nearly half of all cases) or other hypercoagulable states. Hepatic venous congestion can also result from right-sided heart failure or other cardiopulmonary diseases that increase central venous pressure or from mechanical compression or compartment syndrome that impedes hepatic venous outflow. This congestive hepatopathy can ultimately lead to fibrosis, portal hypertension, and liver failure. Portal vein thrombosis may also occur and cause portal hypertension without cirrhosis. Initial therapy is anticoagulation with low-molecular-weight heparin , and endoscopic screening/treatment; beta-adrenergic receptor blockade ( propranolol or nadolol ) for prophylaxis of variceal bleeding are also recommended. Liver transplantation may ultimately be required in chronic cases. A multicenter retrospective cohort study of pregnancies in 45 women previously diagnosed with Budd-Chiari and/or portal vein thrombosis reported that 24% of first pregnancies ended in pregnancy loss ; two women had variceal bleeding and one developed pulmonary embolism but there were no maternal deaths. “ Shock liver ” syndrome can occur in the setting of perioperative hypotension, critical illness with septic shock or cardiac arrest, pulmonary embolism, heart failure, or heatstroke, which can cause disruption of hepatic arterial and/or portal venous inflow, resulting in acute ischemic/hypoxic hepatitis, especially in the setting of other coexisting liver disease.

Wilson disease is a condition of reduced copper excretion in which gradual copper accumulation in the liver can lead to cirrhosis, while rapid accumulation may result in acute liver failure. Patients may also develop neurologic, ophthalmologic, and renal dysfunction. Fertility is generally reduced, but continuing treatment with copper-chelating agents during pregnancy can reduce the risk of spontaneous abortion and result in positive outcomes. Hemochromatosis is a condition of iron accumulation that results in arthropathy, skin pigmentation, diabetes, hypopituitarism, hypogonadism, heart failure, and liver cirrhosis. Phlebotomy (with or without a chelating agent) to deplete iron stores markedly improves survival and prevents most of the complications. Alpha-1 antitrypsin deficiency results in uncontrolled tissue degradation, which may lead to emphysematous changes in the lung and liver cirrhosis. Pregnancy can be complicated by fetal growth restriction, preterm labor, and pneumothorax or other respiratory decompensation.

Hepatotoxicity can result from a variety of exposures. Acetaminophen (paracetamol) , involved in 20% of drug overdoses during pregnancy, is metabolized by the liver into highly reactive oxides. If their formation exceeds the binding capacity of glutathione, maternal and fetal hepatic injury occurs. Treatment with N- acetylcysteine within 16 hours of acetaminophen ingestion may bind toxic metabolites in both the mother and the fetus and improve outcomes. Alcoholic hepatitis can result from the acute ingestion of large amounts of alcohol, and chronic alcohol ingestion may lead to cirrhosis. Other agents that have the potential to cause hepatotoxicity are antiretroviral drugs for HIV infection, propylthiouracil for hyperthyroidism, alpha-methyldopa and labetalol for hypertension, isoniazid for tuberculosis, statins for antiphospholipid syndrome or hyperlipidemia, mushrooms and herbal supplements , and industrial agents .

Hyperemesis gravidarum occurs in 0.3% to 3% of pregnancies and is characterized by a severe and persistent form of nausea and vomiting that can lead to dehydration and electrolyte imbalances, as well as elevated liver transaminases, mild jaundice, and transient hyperthyroidism (see Chapter 17 ). Obstetric ultrasonography should rule out multiple pregnancy or molar pregnancy. Adverse pregnancy outcomes are rare but may occur in women who fail to gain adequate weight during pregnancy.

Intrahepatic cholestasis of pregnancy occurs with an incidence ranging from less than 2% in Europe up to 25% in some populations of South America, with the large variation possibly related to population genetics. Other risk factors include multiple gestation, advanced age, and HCV infection. Proposed causes include genetic canalicular transporter mutations that alter phospholipid or bile salt transport across hepatocyte membranes, as well as abnormal steroid hormone profiles, resulting in pruritus and elevated serum bile acid levels during the second or third trimester. Jaundice is unusual.

Intrahepatic cholestasis of pregnancy has minimal impact on maternal health. Vitamin K malabsorption may lead to coagulopathy and an increased incidence of postpartum hemorrhage; however, contemporary studies have found no increased risk for obstetric bleeding or neuraxial hematoma. Laboratory values should be checked before administration of neuraxial analgesia. While maternal outcome is generally good, there is an increased risk for preterm delivery, fetal compromise, and intrauterine fetal death in women who have a total bile acid concentration > 100 µmol/L.

Treatment with ursodeoxycholic acid or other medications does not reduce the risk of adverse outcomes and is no longer recommended. Delivery before 37 weeks’ gestation is recommended to minimize fetal complications. Recurrence of the disease is common in subsequent pregnancies.

Acute fatty liver of pregnancy (AFLP), or reversible peripartum liver failure, has increased in incidence in recent decades to 28.9 per 100,000 pregnancies and is the most common cause of cirrhosis in pregnancy. It is more common in twin gestations, nulliparity, and male fetuses, and it has been associated with preeclampsia and HELLP syndrome. The disease is characterized by microvesicular fatty infiltration of the liver (and possibly kidney) believed to be caused by defective beta oxidation of fatty acids, usually in the third trimester. In AFLP, genetic enzymatic defects in the fetus (e.g., fetal long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency) and placenta are thought to cause toxic free fatty acid metabolites to build up in maternal hepatocytes. Early nonspecific symptoms include anorexia, nausea, emesis, malaise, fatigue, and headache. Jaundice, edema, hypertension, hypoglycemia, diabetes insipidus, and encephalopathy may develop. Progression to fulminant hepatic and renal failure, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) can be rapid. AFLP may be misdiagnosed as preeclampsia or HELLP syndrome because of a similar constellation of presenting symptoms. After additional laboratory tests the definitive diagnosis can be made. AFLP is associated with lower fibrinogen levels and greater likelihood of renal dysfunction than HELLP syndrome. Rarely, percutaneous or transjugular liver biopsy to identify microvesicular fatty infiltration of hepatocytes may be needed for diagnosis in indeterminate cases.

AFLP is a medical emergency requiring rapid evaluation and treatment. Hepatic failure and fetal death may occur within days. After diagnosis, immediate delivery of the fetus or termination of the pregnancy is recommended. Additional supportive care includes transfusion, mechanical ventilation, dialysis, plasmapheresis, antibiotics, and N- acetylcysteine. Mode of delivery is not as critical as is doing so expeditiously. Liver transplantation may be indicated in severe cases. The anesthesia provider should anticipate postpartum hemorrhage, establish adequate intravenous access, and ensure that cross-matched blood is immediately available. The use of neuraxial anesthesia may be limited by coagulopathy, encephalopathy, ascites, respiratory compromise, or other contraindications. If liver function testing and clinical symptoms do not improve quickly after delivery, liver transplantation may be required.

Improvements in diagnosis and management have reduced maternal mortality (once as high as 85%) to 12% to 18%. Maternal mortality most commonly occurs from liver failure, acute kidney injury, and hemorrhage. Recovery typically occurs within 1 to 3 weeks, though it is unclear if there are significant long-term maternal sequelae. Perinatal mortality may be as high as 66% as a result of the maternal milieu as well as preterm delivery; however, outcomes are better if the disease is recognized early.

Hepatic rupture is a rare event that may complicate preeclampsia, eclampsia, HELLP syndrome, and AFLP, or it may be an isolated event. By definition, spontaneous hepatic rupture of pregnancy occurs in the absence of antecedent trauma. Instead, rupture is preceded by an intraparenchymal hepatic hematoma. The strong association with preeclampsia suggests that periportal hemorrhagic necrosis, hypertension, and coagulopathy may lead to hematoma formation. With expansion of the hematoma, the hepatic capsule is progressively distended and dissected from the parenchyma, leading to rupture. Primary hepatic pregnancy with embryonic implantation on the liver is another rare condition that can result in liver hemorrhage and shock. In the early postpartum period, growth of hepatic hemangiomas, adenomas, or other potentially hemorrhagic masses may occur.

Diagnostic ultrasonography, computed tomography, magnetic resonance imaging, angiography, technetium scintigraphy, and exploratory laparotomy may demonstrate the expanding hematoma before rupture. Hematomas contained within the liver may be conservatively managed with intravenous fluids and blood products. More aggressive treatments include open laparotomy, hepatic artery ligation or embolization, and compression of bleeding points with hepatic packing. Recombinant factor VIIa, although controversial, may be considered in the presence of intractable hemorrhage, and liver transplantation can be considered as a last resort. Maternal and fetal mortality rates with current therapy are 17% and 38%, respectively.