Grant: Operating Grant

Patients with primary biliary cirrhosis (PBC) develop progressive liver disease and often require liver transplantation. The cause of disease is unknown. It is thought to occur as a result of an infection in subjects that are more susceptible to disease than others. We found evidence of virus infection in patients with primary biliary cirrhosis. We saw virus like particles by electron microscopy in patients liver tissues and then obtained the viral genomic DNA sequences. We found that most patients with PBC have evidence of viral infection. Since then we have conducted clinical studies using anti-viral therapy. We found that PBC patients treated with combination anti-retrovirus therapy experienced significant reversal of the disease process. This provides some circumstantial evidence for a retroviral infection. Although we could show significant improvements, the changes were not substantial and we are now looking for better antiviral regimens. Now we have found a mouse model with a similar virus infection that develops a similar biliary disease. Importantly, we found that antiviral therapy blocks the development of the disease in this mouse. Now we are using this model to find antiviral treatments for patients with PBC. In the laboratory, we have isolated the virus in culture as a proof that patients are infected. Now we are now trying to find diagnostic tools to detect viral infection and monitor response to antiviral treatment. We are also trying to find out how the virus triggers specific aspects of the disease to find better therapies.