Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 61. Viral Hepatitis

Symptomatic hepatitis has become less common in pregnant women over the past 15 years. There are at least five distinct types of viral hepatitis: hepatitis A, hepatitis B, hepatitis D caused by the hepatitis B-associated delta agent, hepatitis C, and hepatitis E. Other agents such as hepatitis G virus (GBV-C) and TT virus do not cause hepatitis. All hepatitis viruses except hepatitis B are RNA viruses. Disorders to consider in the differential diagnoses of viral hepatitis during pregnancy are shown in Table 61-1.

TABLE 61-1. Disorders to Consider in the Diagnosis of Viral Hepatitis in Pregnancy

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CLINICAL PRESENTATION

Infections are most often subclinical. When clinically apparent, nausea and vomiting, headache, and malaise may precede jaundice by 1 to 2 weeks. Low-grade fever is more common with hepatitis A. When jaundice develops, symptoms usually improve. Serum transferase levels vary, and their peaks do not correspond with disease severity. Peak levels of 400 to 4000 U/L are usually reached by the time jaundice develops. Serum bilirubin typically continues to rise despite falling aminotransferase levels and peaks at 5 to 20 mg/dL. There usually is complete clinical and biochemical recovery within 1 to 2 months in all cases of hepatitis A and most cases of hepatitis B.

Most fatalities are due to fulminant hepatic necrosis, which in later pregnancy must be distinguished from acute fatty liver. About 50 percent of the patients with fulminant hepatitis have infection with the B virus, and coinfection with the delta agent is common. Hepatic encephalopathy is the usual presentation of patients with fulminant hepatitis, and mortality is 80 percent.

HEPATITIS A

This 27-nm RNA picornavirus is transmitted by the fecal–oral route. The infection is usually spread by ingestion of contaminated blood or water, and the incubation period is about 4 weeks. Individuals shed virus in their feces, and during the relatively brief period of viremia, their blood is also infectious. Signs and symptoms are nonspecific, and the majority of cases are anicteric and usually mild. Early serological detection is by identification of IgM antibody that may persist for several months (see Table 61-2). During convalescence, IgG antibody predominates, and it persists and provides subsequent immunity.

TABLE 61-2. Simplified Diagnostic Approach in Patients with Hepatitis

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Active immunization using formalin-inactivated viral vaccine is more than 90-percent effective. The Centers for Disease Control and Prevention (CDC) recommends consideration for vaccination of susceptible persons traveling to high-risk countries, illicit drug users, those with chronic liver disease or clotting-factor disorders, and food handlers. Passive immunization for the pregnant woman recently (within 2 weeks) exposed by close personal or sexual contact with a person with hepatitis A is with 0.02 mL/kg immune globulin.

The effects of hepatitis A on pregnancy are not dramatic in developed countries. However, both perinatal and maternal mortality are substantively increased in underprivileged populations. Treatment consists of a balanced diet and diminished activity. Women with less severe illness may be managed as outpatients.

There is no evidence that hepatitis A virus is teratogenic and transmission to the fetus is negligible. Even so, preterm birth may be increased and neonatal cholestasis has been reported.

HEPATITIS B

This infection is found worldwide but is endemic in some regions, especially in Asia and Africa. Hepatitis B is caused by a DNA hepadnavirus that is a major cause of acute hepatitis and its serious sequelae, namely, chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B infections are found most often among intravenous drug abusers, homosexuals, health-care personnel, and those requiring frequent blood products (i.e., hemophiliacs). It is transmitted by infected blood or blood products, and it is sexually transmitted by saliva, vaginal secretions, and semen. Because of similar modes of transmission, coinfection with human immunodeficiency virus type 1 (HIV-1) is common and has increased liver-related morbidity.

After infection, the first serological marker is HBsAg (see Figure 61-1). The HBeAg antigen signifies intact viral particles that invariably are present during early acute hepatitis; however, its persistence indicates chronic infection. After acute hepatitis, approximately 90 percent of persons recover completely. Of the 10 percent who are chronically infected, about a fourth develop chronic liver disease. Those seropositive for HBeAg are at greatest risk for hepatocellular carcinoma.

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FIGURE 61-1 Acute hepatitis B—appearance of various antigens and antibodies. ALT, alanine aminotransferase; HBC, hepatitis B core; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen. (From Dienstag JL, Isselbacher KJ. Acute viral hepatitis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al: (eds.): Harrison’s Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill, 1998, p. 1677.)

As with hepatitis A, the clinical course of acute hepatitis B is not altered by pregnancy in developed countries. Treatment is supportive, and as with hepatitis A, the likelihood for preterm delivery is increased. Most infections are chronic, asymptomatic, and diagnosed at prenatal screening. These women are considered to have chronic hepatitis; however, antiviral treatment is generally not given during pregnancy.

Transplacental viral infection of the fetus is not as common as once thought. Viral DNA is rarely found in amnionic fluid or cord blood, and most neonatal infection is vertically transmitted by peripartum ingestion of infected maternal fluids including breast milk. Mothers with hepatitis B surface and e antigens are more likely to transmit the disease to their infants, whereas those positive for anti-HBe antibody are not infective. Infants infected with hepatitis B are generally asymptomatic and 85 percent become chronically infected if not given active and passive immunization shortly afterbirth.

Prevention of Neonatal Transmission

The Centers for Disease Control (June 28, 2002 MMWR 51(25);549–552, 563) estimated that from 1987 to 2000, perinatal infection in the United States was reduced by 75 percent. Neonatal infection can usually be prevented by prenatal screening, with infants of seropositive mothers given hepatitis B immune globulin very soon after birth. This is accompanied by the first dose of a three-dose hepatitis B recombinant vaccine. For high-risk mothers who are seronegative, vaccine can be given during pregnancy.

HEPATITIS D

Also called delta hepatitis, this virus must coinfect with hepatitis B and cannot persist in serum longer than hepatitis B virus. Transmission is similar to hepatitis B. Chronic infection with B and D hepatitis produces more severe disease. Neonatal transmission is unusual because neonatal hepatitis B vaccination usually prevents delta hepatitis.

HEPATITIS C

Transmission of hepatitis C infection appears to be identical to hepatitis B. After acute infection, anti-C antibody is not detected for an average of 15 weeks, and, in some cases, it is not detectable for a year. Antibody usually does not prohibit transmission. In fact, 86 percent of those with anti-HCV positive antibodies had hepatitis C virus RNA and thus were infective. Persistent disease is common after hepatitis C infection.

Perinatal outcome is not adversely affected in anti-HCV positive women compared with seronegative controls, even when viral load exceeds 500,000 copies/mL. The primary concern is that hepatitis C infection is transmitted vertically to the fetus–infant, and the rate varies between 3 and 6 percent. The risk appears to be greater when the mother is coinfected with HIV. As in adult-to-adult transmission (horizontal), antibody is not protective. Currently, there are no methods to prevent transmission at birth. Because of this, the Center for Disease Control does not recommend screening in pregnant women; however, neonates of known anti-HCV-positive mothers should be tested and provided follow-up.

HEPATITIS E

This is a waterborne virus that is enterically transmitted and epidemiologically has features resembling hepatitis A. Serological confirmation is currently not widely available. Preliminary evidence in infected pregnant women suggests a high incidence of vertical transmission, including transplacentally. There is some evidence that it is more severe in pregnancy, especially when acquired late.

HEPATITIS G

It is a blood-borne infection and is usually seen with hepatitis C coinfection. It does not cause hepatitis.

CHRONIC HEPATITIS

This is a disorder of varying etiology that is characterized by continuing hepatic necrosis, active inflammation, and fibrosis that may lead to cirrhosis and ultimately liver failure. By far, most cases are due to chronic infection with either chronic hepatitis B or C viruses. Another cause is autoimmune chronic hepatitis, characterized by high serum titers of homogeneous antinuclear antibodies.

Most cases of acute viral hepatitis B and C are anicteric and are clinically unnoticed. Similarly, most cases of chronic hepatitis are asymptomatic and are diagnosed by elevated serum transaminase levels obtained for screening (e.g., during blood donation). When present, symptoms are nonspecific and usually include fatigue. Diagnosis is made by liver biopsy. However, treatment is given in most patients after serological or virological diagnosis. There is now considerable experience with treatment of chronic viral hepatitis in nonpregnant patients, and a third of patients can be cured. In some patients, cirrhosis with liver failure or bleeding varices is the presenting finding.

Most young women with chronic hepatitis either are asymptomatic or have only mild liver disease. For seropositive, asymptomatic woman, there usually is no problem with pregnancy. With symptomatic chronic active hepatitis, pregnancy outcome depends primarily on the intensity of the disease and whether there is portal hypertension. The few women whom we have managed have done well, but because their long-term prognosis is poor, they should be counseled regarding possible liver transplantation as well as abortion and sterilization options.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 49, “Gastrointestinal Disorders.”