An alternative infectious agent has recently been proposed as trigger of PBC when a human retrovirus was identified both in liver tissue and hilar lymph nodes from PBC patients. EM analysis of liver tissue obtained from PBC patients revealed retrovirus compatible particles in BECs. In periportal lymph nodes, mouse mammary tumor virus (MMTV) was detected and correlated with aberrant distribution of PDC-E2 in perisinusoidal cells. Homogenates of these periportal lymph nodes also had the capacity to infect BEC cultures inducing marked phenotypic change, and this effect could be abolished by irradiation of the culture media, suggestive of an infectious agent [142, 143] . Retroviral infection hypothetically could cause BEC damage either through a direct viral cytopathic effect, through cross-reactivity between viral protein and self-PDC, a "molecular mimicry" model, or virus-induced apoptosis [84] . Retroviral infection would also provide explanations for some key phenomena in PBC. PBC can recur rapidly after transplantation with all of the clinical manifestations including the detection of AMA in serum [144] , the aberrant expression of the AMA-reactive protein on BEC [145] , and histologic evidence of disease in up to 45% of patients [146] . In this respect, the observation of an association of more potent immunosuppressive therapy following transplant and earlier and more aggressive recurrence of PBC [147] is also of interest. MMTV replication is regulated in part by a progesterone-responsive glucocorticoid regulatory element in the promoter region, offering an alternative explanation for the female preponderance seen with PBC [148] .