SAN FRANCISCO – Physicians in the United States should not be too quick to cross hepatitis E off their lists of possible diagnoses for patients who have not traveled abroad, researchers with the Centers for Disease Control and Prevention advise.

They performed serologic and molecular testing in 123 patients with acute hepatitis-like illness that was not hepatitis A, B, or C, and found that 22% had hepatitis E, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases.

Nearly two-thirds of these patients had no history of recent international travel. Slightly more than a quarter had undergone organ transplantation.

"This work is very important to build awareness about hepatitis E in the U.S., where this disease is not reportable and [its] epidemiology ... is unknown," lead investigator Dr. Jan Drobeniuc said in an interview. "Our work shows that this disease is more common in the U.S. than previously thought."

Although physicians have usually relied on a travel history to tip them off to the presence of hepatitis E, these surveillance data suggest that infection in the United States may in fact be more common among nontravelers.

"I think that hepatitis E should enter into the differential diagnosis of hepatitis even for people who did not travel abroad," Dr. Drobeniuc said. "Previously, this prerequisite was kind of biasing the physicians – their first question would be, ‘Did you travel?’ If you didn’t travel, they just dismissed the case. So I think this travel-nontravel situation has to be removed to prevent bias for the physicians, and [they should] just do laboratory testing to determine the disease."

Research suggests that about one in five people in the United States has antibodies to hepatitis E (J. Infect. Dis. 2009;200:48-56). "So the obvious question would be, why is there no acute disease, why don’t we see the actual cases?" noted Dr. Drobeniuc, senior service fellow and microbiologist with the CDC. "Probably the reason is it’s not reportable."

To get a better handle on its epidemiology, the CDC established a passive surveillance system for physicians who had patients with hepatitis that did not have a readily identifiable cause.

The investigators tested specimens from 123 patients who had acute hepatitis-like illness with jaundice and/or elevated liver function test results, were referred to the surveillance system between 2005 and 2011, and were serologically confirmed not to have hepatitis A, B, or C.

According to study results reported in a poster session at the meeting, 27 (22%) of the patients had hepatitis E, based on the presence of antiviral IgM antibodies in serum or viral RNA in serum or stool.

The patients had been referred from 14 states; the states accounting for the largest shares were Texas and Illinois. The median age was 42 years, and the majority of patients were male (59%) and white (52%).

Viral genotyping in a subset of patients showed that three-fourths had genotype 3. And phylogenetic analysis showed that these strains were genetically similar to those seen previously in indigenous cases of hepatitis E and in swine in the United States.

"Our work shows that this disease is more common in the U.S. than previously thought."

Twenty-six percent of the patients were organ transplant recipients, a population that seems to be at high risk for developing persistent disease. "This most likely is related to the fact that they are immunosuppressed and they do not develop a proper immune response to the infection," Dr. Drobeniuc explained. All of the recipients who had viral genotyping were found to have genotype 3.

Fully 63% of the patients had not traveled outside the United States in the previous 2 months. Compared with travelers, nontravelers were significantly older, less likely to be of South Asian race/ethnicity, and more likely to be organ transplant recipients. All of the cases of genotype 3 occurred among nontravelers.

It was not clear how the patients studied became infected with hepatitis E. Their clinical course attested to the fact that this infection can sometimes be severe, as two patients experienced fulminant hepatic failure, and one of them died.

Because the surveillance system was passive and relied on the discretion of referring physicians, the rate of hepatitis E seen "most likely does not reflect the incidence of hepatitis E in the United States," he commented. Additionally, it was not possible to accurately assess temporal trends.

"Now we are expanding this passive surveillance to a more active approach," with testing in cases referred by laboratories, Dr. Drobeniuc noted. Given that viremia is usually short-lived in infected patients, a particular aim is to identify more cases in the acute phase, so that the virus can be isolated and genotyped. "An active approach will probably give a much better picture of hepatitis E in the United States," he concluded.

Dr. Drobeniuc reported having no conflicts of interest.

Lack of Travel History Does Not Rule Out Hepatitis E