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Vol. LXIII, No. 17
August 19, 2011

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CC Grand Rounds Looks at Hepatitis E

Dr. Jay Hoofnagle

NIDDK’s Dr. Jay Hoofnagle delivers a recent Great Teachers Lecture, part of the Clinical Center’s Grand Rounds series.

Photo: Bill Branson

Hepatitis E, the fifth form of viral hepatitis, is the youngest, most poorly understood, most mysterious, and, recently, most challenging of the five, according to Dr. Jay Hoofnagle, director of the NIDDK Liver Diseases Branch and long-term senior investigator and liver expert. He delivered “Hepatitis E, an Emerging Infectious Disease,” at a recent Great Teachers Lecture during Clinical Center Grand Rounds.

Proof for a fifth type of viral hepatitis, Hoofnagle recalled, was first announced in 1980 when two groups of researchers—one from NIAID’s Laboratory of Infectious Diseases—found that outbreaks of severe hepatitis in India were not due to hepatitis A or hepatitis B.

These large epidemics had always been mentioned as “classical” examples of hepatitis A—infectious hepatitis caused by sewage contamination of the water supply, typically found in underdeveloped areas of the world (Asian subcontinent, sub-Saharan Africa, Central America). The fact that it wasn’t hepatitis A (or B) was an eye-opener and led to its first, somewhat cumbersome name “epidemic non-A, non-B hepatitis.”

Hoofnagle said these first reports triggered a search for its cause. One year later, researchers from Moscow Institute of Virology made the seminal discovery. Using the same methods that led to the discovery of hepatitis A (immune electron microscopy), they found a small virus particle in stool specimens from Russian soldiers who had fallen ill with hepatitis in Afghanistan.

That breakthrough soon led to the identification of hepatitis E as an RNA virus, development of diagnostic tests for antibody and careful definition of its course, complications and means of spread.

Hepatitis E was virtually non-existent in the United States, where only “imported” cases were found. It caused an acute hepatitis that was occasionally severe and could be fatal, but never persistent or chronic or causing cirrhosis.

Hepatitis E appeared to be a problem limited to the underdeveloped world. For the U.S. and the developed world, creating tests for its diagnosis or vaccines for its prevention did not seem critically important.

Recently, Hoofnagle reported, these concepts have changed. Hepatitis E does occur in the U.S., but as sporadic cases—not in epidemics and not linked to drinking polluted water or traveling abroad. The disorder can be severe and fatal and can cause chronic infection and lead to cirrhosis.

Curiously, most cases are in older men. Why have these concepts about hepatitis E changed so much?

The reason, Hoofnagle said, is that hepatitis E occurs in two distinct forms caused by different strains (or “genotypes”) of the virus, which have different means of spread and can have different outcomes.

Epidemic hepatitis E that occurs in Asia, Africa and Central America is caused by genotypes 1 and 2—viruses that are native to humans.

Sporadic hepatitis E that occurs in the Western or “developed” world (which now includes China) is caused by genotypes 3 and 4—viruses that are native to swine (pigs and wild boars) and infect humans secondarily.

Similar hepatitis E viruses are also found in deer, elk, goats, sheep and even the black rat.

So far only the swine form of hepatitis E has been proven to infect humans. The most likely cause of spread of this form of hepatitis E is eating undercooked pork or wild game. The disease is particularly severe in the elderly and can lead to a chronic infection in persons with immune problems, including transplant patients and people with AIDS, in whom it can eventually lead to cirrhosis.

Many questions about hepatitis E remain. Just how common is it in the U.S.? What can be done to block its spread? Is it treatable and with what antiviral medications?

The mysteries of hepatitis E are unfolding, as are important challenges for research, Hoofnagle noted. Immediate goals are to develop reliable diagnostic tests and means of treatment and prevention. Perhaps a first step, however, is a wider appreciation of the significance and frequency of hepatitis E in the U.S. as an emerging infection.

Research in viral hepatitis has made major inroads into the prevention and control of hepatitis A, B, C and D, Hoofnagle concluded. The fifth form of viral hepatitis is waiting in line; its mysteries are likely soon to be unveiled and lead to similar inroads into its prevention and control. NIHRecord Icon

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