Feb. 19, 2015

Exploring a viral connection to primary biliary cirrhosis

UAlberta researcher defies convention to reveal a new trigger for a rare disease

(Edmonton) For the past decade Andrew Mason has held fast to an idea that much of the world’s scientific community had long since dismissed. Mason, a professor of medicine at the University of Alberta’s Faculty of Medicine & Dentistry and a gastroenterologist at the University of Alberta Hospital, was convinced that a betaretrovirus triggered an autoimmune liver disease. The agent was previously linked with cancer but the low levels of virus made it too difficult to convincingly demonstrate infection. Most researchers don't believe that betaretroviruses can infect humans but today Mason is glad he stuck with it.

In a new study published in the February edition of the journal Alimentary Pharmacology and Therapeutics, Mason, along with colleague Gane Wong, a professor of Bioscience and Medicine at the U of A, found that human betaretrovirus (HBRV) infection is commonly observed in the cells of patients with primary biliary cirrhosis (PBC), a liver disease categorized as autoimmune in nature. According to Mason, the finding provides a level of proof that the virus infects humans and also demonstrates a connection between the virus and liver disease.

“Our publication shows that this virus inserts its DNA into the human genome, where we found the junction regions of virus integration in cells of the biliary epithelium, the site of disease,” explains Mason. “This is the gold standard for demonstrating retrovirus infection. We actually saw over 1,500 unique virus integrations in patients’ samples. So that settles an ongoing debate since the 1970’s saying that a betaretrovirus like ours is not a human pathogen.”

The idea that HBRV could cause a form of cancer was first brought up in the 1970’s. However, because the virus was found at such low levels at the time, the scientific community could not agree on whether it was a true infection. Mason says the discussion reached a stalemate in the 1980s and was eventually ignored once the HIV epidemic emerged. In 1998 the University of Alberta researcher began examining HBRV and its connection to PBC, eventually publishing findings linking the two in the journal Proceedings of the National Academy of Science. The findings though were called into question after another group was unable to find the virus within the liver of PBC patients and challenged the study. Now more than a decade later, Mason says his team is able to offer further and more detailed proof through the advancement of technology and the use of gene sequencing.

“We always thought that autoimmune diseases like PBC looked like virus infections underneath the microscope but people have been unable to find viruses. Because they found autoantibodies they assumed they were autoimmune diseases. But patients with hepatitis C virus make autoantibodies and no one calls this an autoimmune disease. So we are taking the same approach with PBC as with hepatitis C virus infection. Try and knock out the virus with antiviral therapy.”

Primary biliary cirrhosis is a rare disease that affects the bile duct in the liver. It occurs in up to 1 in 500 middle-aged women and is found in about 10 percent of all patients needing liver transplants. Despite the progress being made, Mason says HBRV has still not yet been fully linked as the cause of disease. His team is in the midst of a randomized controlled trial that he hopes will provide further proof. They are following PBC patients who are taking antiretroviral therapy to see if they show clinical improvement.

“Loss of virus equals loss of disease. We have to show that.”

Mason believes the findings offer new avenues of research for future clinical treatment. While answers won’t come quickly, he says they are emerging, offering hope to patients suffering from PBC.

“We’ve seen some improvement in patients with recurrent PBC following liver transplantation using antiviral therapy. Our CIHR funding now is for testing newer medicines in the lab to find better treatments.”
Research funding was provided by Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, Alberta Cancer Foundation, Canadian Liver Foundation, Alberta Health Services and the Li Ka Shing Institute of Virology.

Media inquiries:
Ross Neitz, communications associate
Faculty of Medicine & Dentistry
University of Alberta
780-492-5986 (office);

Canadian PBC Society

Response to Dr. Mason’s latest results

The Canadian PBC Society has contributed to Dr. Mason’s research into the causes of primary biliary cirrhosis and welcomes the latest exciting results. Confirmation of these findings and their implications has the potential to alter the life and treatment of patients with PBC in a dramatic and positive manner. We look forward with anticipation to the results from the next stage of his ongoing study.

We also thank Dr. Mason for his support of the PBC Society and the activities of the North Alberta group.

Barbara Badstober