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 retrovirus infection in patients with primary biliary cirrhosis. 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. We have used this model to find safer and more effective antiviral treatments for patients with PBC. We have now found out that a combination of highly active antiretroviral therapy with Truvada and Kaletra stops disease in the mouse and plan to use this combination to see if it works in patients with PBC. Of interest, a recent case report shows that this combination is associated with normalizing liver tests in a patient with PBC and retrovirus infection.