Hepatic progenitor cells and regeneration in alcoholic steatohepatitis

Details

Supervisors

Lanthier, Nicolas

Faculty

Faculté de médecine et médecine dentaire

Degree label

Master [180] en médecine

Abstract

Abstract Background and aims: The role of liver progenitor cells (LPCs), known as markers of severity in chronic liver disease, remains poorly understood, as well as the impact of macrophages on liver regeneration. We aimed to characterize these cell populations in severe alcoholic steatohepatitis (ASH) and determine whether their activation could be identified as good prognostic factors. Methods: Immunohistochemical studies for LPCs (proliferative or not), macrophages and proliferative hepatocytes were performed on the admission biopsies of 68 patients suffering from severe ASH recruited in 20 different centers in Belgium and France. Patients were first divided in two groups, improvers or non-improvers, according to the change of MELD score at 3 months after baseline. They were then divided in two other groups, responders or non-responders to corticosteroids, according to the Lille score at day 7. Results: In severe ASH, mechanisms of liver regeneration are activated. In our population, we found that the total amount of LPCs was positively correlated to the severity of the disease at screening evaluated by the MELD score. However, no difference of total LPCs, proliferative LPCs, proliferative hepatocytes or macrophages was found between improvers and non-improvers nor between the favorable and unfavorable Lille score groups. No significant difference of survival (at 3 months or overall) was found either between high and low proliferators for hepatocytes or LPCs. As for the study of cell populations, a higher number of macrophages was associated to a more important proliferation of both hepatocytes and LPCs. A higher hepatocyte replication was also correlated to a higher proliferative LPC count. Conclusions: We did not identify hepatocyte proliferation, LPC proliferation or macrophage expansion as prognostic factors in severe ASH. Macrophage expansion was correlated to a more important proliferation of hepatocytes and LPCs, and the proliferation of hepatocytes and LPCs occurred in parallel.