What's New -- Part 2: Viral Hepatitis in Children

Hepatitis C, D, E, and G in Children

Ravi Jhaveri, MD


July 06, 2011

In This Article

Hepatitis E in Children

An 18-year-old, previously healthy girl and her family returned from a year spent in India as missionary workers approximately 3 weeks ago. Since their return, the child has been noted to be fatigued and anorexic with intermittent complaints of nausea. The parents assumed her symptoms were the result of her recently diagnosed pregnancy and the transition back to the United States and treated her symptomatically. However, over the last 4-5 days she has developed jaundice, fever, and now complains of acute abdominal pain. She is evaluated at her obstetric office and hepatitis serology and liver function testing is ordered. However, over the ensuing 24 hours she rapidly deteriorates, requiring intensive care. Over the course of 48 hours, she expires from fulminant hepatic failure.

Clinical Picture of Hepatitis E

Hepatitis E virus (HEV) is also a small, nonenvelope, single–stranded, plus-sense RNA virus. It's about the same size as HAV. HEV is a more recently recognized virus that represents a unique Hepeviridae family with 2 distinct geographic subtypes, the Asian and Mexican strains. Like HAV, transmission is via fecal/oral contact, and outbreaks have been reported in developing countries, though sporadic cases also occur. Inevitably the source of the outbreaks is contaminated water. HEV outbreaks have been reported in areas with war or major conflict and following major natural disasters. In subsequent disruptions in public health infrastructure, you will see HEV outbreaks. In endemic areas including Central and Southeast Asia, North and West Africa, and Mexico, HEV is responsible for most cases of acute hepatitis.

Most patients diagnosed with HEV in the United States are travelers who acquired the virus in a foreign country. Recent data support the emergence of a milder form of the virus that causes subclinical infection in regions in the United States that are likely to be associated with swine exposure or other wild animal exposure, but this is still yet to be fully defined. The attack rate for HEV appears to be 50 times less than seen with HAV. Only 1% of HEV-exposed patients will develop acute infection compared with the 50%-75% attack rate following exposure to HAV.

HEV causes acute hepatitis in about 75% of infected patients. The incubation period is quite varied, ranging from 15-65 days. The symptoms can vary from mild to severe and are virtually identical to HAV or HBV. Typically, symptoms increase with age. There is no chronic infection with HEV, and it has not been shown to cause cirrhosis or hepatocellular carcinoma.

The rate of fulminant hepatic failure is approximately 20 times higher in pregnant patient vs their nonpregnant counterparts and risk increases as pregnancy advances, with third trimester infection associated with a 50% mortality rate. The cause of this devastating impact of HEV during pregnancy is not understood. The relationship between HEV and pregnancy was recognized following a major outbreak in the Darfur region of Sudan. Fulminant hepatic failure is rare in nonpregnant patients.

Diagnosis and Management of HEV

HEV-RNA can be detected in stool from 1 week prior to the onset of symptoms and for more than 2 weeks after the onset.

Figure 4. Clinical and serologic timeline for HEV.
From Jhaveri R. Textbook of Pediatric Infectious Diseases. Editors: Feigin, Cherry, Daimler-Harrison, Kaplan. In Press. WB Saunders: Philadelphia.

As depicted in figure 4, the relationship between serologic markers and clinical symptoms in HEV infection is similar to that of HAV with the exception of a longer period during which HEV RNA is detectable in serum. The pattern follows that seen with other hepatitis viruses in that the viral markers precede symptoms, with antibodies appearing later in the course of infection.

HEV can be detected by testing either for viral RNA or antibody response to the virus. Polymerase chain reaction (PCR) for HEV RNA is available on a research basis for detection of viral genetic material. Testing for immunoglobulin M antibody against HEV is available at several referral laboratories.

Treatment for HEV is symptomatic. The focus in management should be on prevention. In countries endemic for HEV, precautions should be taken to avoid contaminated water and food (boiling water before drinking, peeling fruits and vegetables, avoiding ice in beverages). As part of prenatal counseling, pregnant women should be advised not to travel to countries where HEV is endemic.

What's New With Hepatitis E?

An experimental vaccine for HEV has been developed and tested in a large-scale, phase 2 trial of men in the Nepalese army.[6] Efficacy was 95.5% after 3 doses. A more recent phase 3 trial of healthy adults in China reported 100% efficacy after 3 doses.[7] Economic considerations may limit wide-scale use of this vaccine.


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