Woodchuck colony vital to progress in hepatitis B research

Fighting a deadly virus


(September 3, 1998, Gazette)

By Sonia Glover

Dr. Thomas Michalak is looking to expand his woodchuck colony, an important tool in his research on hepatitis B -- a deadly virus that has affected at least five per cent of the world's population.

Dr. Michalak, of the Molecular Virology and Hepatology Research Laboratory at Memorial's Faculty of Medicine, said the woodchuck model has become a key contributor in his research and is solving some of the mysteries surrounding hepatitis B.

"Some sub-species of woodchucks, also called groundhogs, which occur in Eastern US, are susceptible to the virus which is very similar to that causing hepatitis B," Dr. Michalak told the Gazette. "The animals develop liver disease, including hepatocellular carcinoma, that closely mimics human illness induced by the hepatitis B virus."

In order to continue to make advances in his research, however, Dr. Michalak would like to expand his woodchuck colony and he wants to use Canadian woodchucks. He had been using American woodchucks in the past because the animals were more easily accessible and were proven to carry the hepatitis virus.

But over the past few years the demand for American woodchucks has risen significantly and prices have gone up.

Dr. Michalak's woodchuck colony is one of only a few in the world. The colony offers a rare opportunity to carry out investigations in the natural setting of mechanisms underlying hepatitis B pathogenicity and to assess new methods to treat hepatitis B virus-induced diseases.

The woodchuck model has become the accepted way to test potential drugs and new preventative methods against hepatitis B and, in some situations, drugs against HIV -- to a certain degree, the HIV replication strategy is similar to that of the hepatitis B virus.

Important new information has been generated by Dr. Michalak and his research team over the past few years. One of his recent findings is that the majority of people infected with hepatitis B carry small amounts of the virus even many years after complete clinical recovery from hepatitis.

"The person exposed to the hepatitis B virus can fully recover from the symptoms, but traces of the virus will remain present in the circulation, liver and lymphatic system. Our studies in woodchucks not only fully confirmed this discovery, but also revealed that convalescent animals carry the virus for life; the persisting virus is infectious to healthy animals and is transmittable to offspring. Also, importantly, some of the recovered, apparently healthy animals develop liver cancer within several months after termination of hepatitis.

"So, we've found there is a hidden infection, detectable by sensitive nucleic acid amplification techniques, which follows symptomatic disease, and which may have very important epidemiological and pathogenic implications," explained Dr. Michalak.

"These findings imply that there could be a significant hazard to transplant organs and transfuse blood from individuals who were exposed to hepatitis B in the past. The organ and blood have to be carefully checked to see whether the donor was infected with hepatitis B in the past because the small amounts of the persisting virus could be infectious."

Dr. Michalak added that it would be advisable to carefully screen all donors using currently available molecular assays in research laboratories, however, no such tests are yet licensed or are inexpensive enough for individual blood and organ screening.

While many advances have been made in hepatitis B research, Dr. Michalak said a lot of work is still needed in order to come up with a successful drug to treat the illness.

"We are progressing with the understanding of the molecular and immunological mechanisms of the disease, but at the present time there is still no treatment able to indicate the established infection. Some of the drugs being used now are only successful in a small number of people and they are not eliminating the virus, just temporarily decreasing its amounts and the disease symptoms."

Dr. Michalak often thinks of the day when a cure is found for hepatitis B, but before that can happen, he says more knowledge is needed.

"I want to understand the virus persistence and why the same virus induces various forms of liver disease in different individuals. So, without understanding why the virus produces chronic infection, it will be difficult to find a cure."

He added that the woodchuck colony is important in three areas: basic research, testing of new therapeutic agents, and evaluation of new prevention methods.

Dr. Michalak started his research on hepatitis B as a medical student more than 20 years ago, and when he speaks about the subject you can hear the passion in his voice. He said he will continue to work in this area of research for as long as he is able to attract appropriate resources.

"Many researchers who are now working on HIV and hepatitis C used to work on hepatitis B but I continue to stay with the disease because many basic problems remain unsolved and the understanding of the complexity of virus-host interactions in this disease remains for me very interesting and exciting.

"It is also very rewarding to see my younger co-investigators, graduate students when they become familiar with this important human disease they start to see how many interesting things need yet to be done and how their understanding could contribute to our general knowledge of disease development and viral pathogenicity. Hopefully, some of them could continue to work in the same area of biomedical research."