Grant: Project Grant

Patients with primary biliary cholangitis (PBC) develop progressive liver disease and often require liver transplantation. We found evidence of betaretrovirus infection in patients with PBC and showed that most patients have evidence of viral infection in their bile ducts, the site of disease. In addition, we have conducted several clinical studies using anti-retroviral therapy. To evaluate antiviral medications, we used a mouse model with a similar retrovirus infection that develops biliary disease. Two classes of drugs used to treat patients with HIV were found to be effective in blocking betaretrovirus infection. These two classes of compounds inhibit the retrovirus reverse transcriptase and protease enzymes, respectively. Using this combination, we found that PBC patients experienced significant reversal of the disease process. The improvement in their lab tests and liver biopsy was associated with reduction of virus in the blood. This provides some good evidence for a retroviral infection in patients with PBC. However, only a third of patients could tolerate the medication that inhibits protease enzymes. Accordingly, we looked for a better tolerated antiretroviral treatments and found out that a newer class of medications called integrase inhibitors could block betaretroviral infection. Now we plan to conduct a pilot study using a combination of integrase inhibitors and reverse transcriptase inhibitors in patients with PBC to see if this regimen improves disease without undue side effects.