Complexities of hepatitis virus fascinate researcher

By Sharon Gray

As a medical researcher, Dr. Thomas Michalak sees his work on hepatitis viruses as having more than one aspect.

"We are not only conducting research to try to explain basic mechanisms by which these viruses cause chronic liver diseases and carcinoma, but are also looking at practical treatments against them," he said.

At the Liver Research Laboratory in the Faculty of Medicine, the primary focus is the hepatitis B virus. But because the central step in the replication cycle of this virus is similar to that of the AIDS virus, the same research tools can be used to study the effectiveness of potential drugs against both hepatitis and HIV.

Therapeutic agents which would eliminate virus-infected cells without harming the entire host are being tested, and Dr. Michalak is collaborating with other Canadian colleagues to assess the effectiveness of 3TC -- a compound recently approved in Canada for the treatment of HIV infection -- in preventing the liver carcinoma which is a consequence of chronic hepatitis B in some patients.

Dr. Michalak's hepatitis B virus research uses a closely related virus found in some populations of woodchucks. "We have enough evidence to say that different forms of liver diseases induced by the hepatitis B virus result from a complex interplay between the virus, the host immune responses and genetic -- and probably -- environmental factors. This situation is complicated by the fact that the virus is able to mutate, changing its genomic structure, and adapt to the environment to escape particular defense mechanisms."

Dr. Michalak has discovered that the virus can infect not only the liver, but also cells of the immune system. "In fact, contrary to accepted thinking, the virus can be present in the lymphatic system but not in the liver," he said.

Nearly five per cent of the world's population is infected with hepatitis B, and in Canada about a quarter of a million people are affected. In some native groups, chronic infection occurs in more than 20 per cent of individuals. During the past five years, the medical school's Liver Research Laboratory has attracted more than a million dollars in funding from the Medical Research Council of Canada and private companies in Canada, the U.S. and Europe.

In collaboration with the Scripps Research Institute in California, Dr. Michalak has discovered that even in patients who have had a full clinical recovery from acute hepatitis B infection, the genome can persist for many years. Graduate student Carla Coffin has found that low levels of the genome can be transmitted in woodchucks from mother to baby, and with the help of a Graduate Studentship Award from the Canadian Liver Foundation she is studying whether this predisposes such babies to liver carcinoma.

After many years of working on hepatitis B, Dr. Michalak is deeply aware that the study of this complex disease poses continuous intellectual and technological challenges. "Research in this field fuses basic science with important clinical problems, providing an open ground for interdisciplinary interactions. As an M D with former clinical training, I see my research through a prism of patient suffering. As a scientist I try to use the knowledge gained in the most practical way."