Primary biliary cirrhosis: new thoughts on pathophysiology and treatment

Primary biliary cirrhosis (PBC) is an idiopathic inflammatory hepatic disorder characterized by granulomatous destruction of small bile ducts and formation of antimitochondrial antibodies. Having found that most patients with PBC have antibody reactivity to retroviral proteins, we recently cloned a retroviral sequence directly from biliary epithelium extracted from PBC livers. Further evidence for an infectious etiology of PBC has been derived from an in vitro model using normal biliary epithelial cells in culture with lymph node extracts from patients with chronic liver disease. In this model, biliary epithelial cells cocultivated with PBC lymph nodes developed a specific phenotype of PBC with immunohistochemical evidence of antimitochondrial antibody reactivity. This model has been used to show that patients with PBC harbor a transmissible agent that may be related to the cloned retrovirus. Pilot studies using antiretroviral treatment for patients with PBC have also supported the involvement of a retrovirus in the disease process. Because the antiretroviral therapy was tolerated without undue adverse events, a multicenter controlled trial is being established to determine whether patients with PBC derive significant benefit from this new line of investigation and management.