Novel Hepatitis Viruses in Horses Reviewed

Divers noted that additional research is needed to fully understand these new hepatic viruses and their clinical impact, if any, on horses.

Photo: Erica Larson, News Editor

Not long ago, when a veterinarian dealt with acute liver inflammation in a horse, he or she was likely diagnosing Theiler's disease, or serum hepatitis. But there are three new hepatitis viruses in town, all initially described in the past two years. What are these viruses, and are they clinically relevant?

At the 2014 American College of Veterinary Internal Medicine Forum, held June 4-7 in Nashville, Tennessee, Thomas J. Divers, DVM, Dipl. ACVIM, AVECC, reviewed these new viruses and explained how they might affect horses.

Theiler's Disease Reviewed

Sir Arnold Theiler first described serum hepatitis in the first half of the 20th century when he described "hundreds of cases of a highly fatal form of hepatitis that occurred in horses following vaccination against African horse sickness, by the simultaneous administration of infectious virus and convalescent equine antiserum," Divers said.

Since then, he said, it has been diagnosed periodically throughout the 20th and 21st centuries. Divers said a recent review of 13 Theiler's cases at the Cornell University equine hospital in the past 25 years indicated that four of those horses had received equine serum or plasma in the prior 30 to 70 days, while the other nine horses were all diagnosed between June and November.

In all the horses that underwent necropsy, Divers said veterinarians found severe centrilobular hepatocyte necrosis (tissue death), and Alzheimer type II astrocytes (a type of cell in the brain's cerebral cortex associated with hepatic encephalopathy).

Theiler's Disease-Associated Virus (TDAV)

The first of the novel hepatitis viruses Divers described was TDAV, which he and his team came across when consulting on an outbreak in 2011.

"Two and a half months earlier, horses from the affected farm had developed botulism," he explained. "Twenty-two horses were treated with botulinum antitoxin from two separate sources."

Of the 17 horses treated with one of the antitoxins, eight developed evidence of hepatitis seven to nine weeks after intravenous treatment, he said. None of the horses treated with the other type of antitoxin or the 53 other horses on the farm that had not received any antitoxin developed hepatitis, he noted.

Divers and colleagues identified the new virus—found in the serum of two horses with acute hepatitis and in the botulinum antitoxin those two horses received—as belonging to the Flaviviridae family (in which viruses such as West Nile virus spread through arthropod vectors). The team ultimately tested all 17 horses that received that antitoxin and found that all were positive for TDAV; eight of those horses developed acute hepatitis. One of the three horses used in the production of the antitoxin also tested positive for TDAV.

"The single positive donor horse was TDAV-negative six months following the outbreak, and there have been no further reports of Theiler's disease-associated virus with the use of (the antitoxin)," Divers said.

Two of the TDAV-positive horses on the affected farm remained positive two years after the initial outbreak, and the level of virus in the bloodstream has remained unchanged, Divers noted. However, no additional horses have tested positive on that farm, "suggesting direct horse-to-horse transmission or transmission by insect vectors may not occur or is not common," he said.

Thus far, researchers have not yet established a causative relationship between TDAV and Theiler's disease, Divers said, and it remains unclear as to the discovery's clinical importance . But the team continues to study the association between TDAV and Theiler's disease, he relayed.

Nonprimate Hepacivirus (NPHV)

Divers then moved on to NPHV, which scientists initially reported in a small number of dogs in 2011 and identified in horses in 2012. Researchers first detected the virus in the serum of eight of 103 normal horses. Of those 103 horses, Divers said 35% tested positive for NPHV antibodies.

Divers said NPHV is a member of the Heptacivirus genus (also part of the Flaviviridae family of viruses) and noted that "currently, there is no documented association between NPHV infection and hepatic disease in horses, although in the initial report of the virus there was no testing for hepatic disease and the horses were presumed to be healthy." The virus is believed to be hepatotropic (affecting the liver), Divers said, and a low percentage of infected horses maintain chronic infection.

Equine Pegivirus (EPgV)

Finally, Divers touched on EPgV, the most-recently reported hepatitis virus, discovered in 2013.

"This virus is clearly divergent from TDAV, although both are in the pegivirus genus," he said.

Pegiviruses aren't known to cause clinical disease in horses; however, researchers have found some association with elevated serum liver enzymes and EPgV-positive horses, Divers said.

Researchers also tested a herd of healthy horses over a four-year period:

  • At the first test, six of 19 horses tested positive for EPgV;
  • At the second test, six of 29 horses tested positive; and
  • At the third test, four of 27 horses tested positive.

Of the positive horses, Divers said two appeared to be carriers for at least 3 ½ years.

Take-Home Message

Divers noted that additional research is needed to fully understand these new hepatic viruses and their clinical impact, if any, on horses.

"Our long-term research goals are to advance the understanding of the role these viruses may play in equine liver disease; in the etiology, pathogenesis, and epidemiology of Theiler's disease; and finally, to apply knowledge of the natural history of the disease to the control, prevention, and possibly eradication of serum hepatitis in horses," he concluded.

About the Author

Erica Larson, News Editor

Erica Larson, news editor, holds a degree in journalism with an external specialty in equine science from Michigan State University in East Lansing. A Massachusetts native, she grew up in the saddle and has dabbled in a variety of disciplines including foxhunting, saddle seat, and mounted games. Currently, Erica competes in eventing with her OTTB, Dorado.

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