The finest branches of the biliary tree might induce biliary vascularization necessary for biliary regeneration

BACKGROUND/AIMS: The finer branches of the biliary tree play an important role in biliary regeneration. They are consistently escorted by microvessels. Defects in the vascularization of these structures could impair bile duct regeneration. Therefore, we investigated the pattern of the escorting microvessels during the development of bile duct loss in the human liver, using chronic rejection as a model. METHODS: The number of interlobular bile ducts, bile ductules and extraportal biliary cells with and without escorting microvessels and the expression of VEGF-A were studied in follow-up biopsies of 12 patients with chronic rejection and 16 control patients with acute rejection without progression to chronic rejection. RESULTS: The controls showed a proliferation of bile ductules at 1-week and 1-month. Proliferation of bile ductules without microvessels preceded proliferation of bile ductules with microvessels. Proliferation of the microvascular compartment followed biliary proliferation. This sequence of events was not observed in the chronic rejection group, in which all biliary structures decreased in time. VEGF-A expression was increased at 1-week and 1-month in both groups. CONCLUSIONS: An immediate proliferative response of the finer branches of the biliary tree followed by proliferation of the microvascular compartment after biliary injury seems to be a prerequisite for bile duct regeneration.