Liver regeneration and the role of hepatic progenitor cells in alcoholic steatohepatitis

Adrienne Lejeune(1,2), Peter Stärkel(1,2), Alexandre Louvet(3), Axel Hittelet(4), Céline Bazille(5), Boris Bastens(6), Hans Orlent(7), Luc Lasser(8), Xavier Dekoninck(9), Sergio Negrin Dastis(10), Jean Delwaide(11), Anja Geerts(12), et al. Published in the journal : November 2018 Category : Mémoires de Recherche Clinique

Summary :


The role of liver progenitor cells (LPCs), which are known as severity markers in chronic liver diseases, remains poorly understood, as is 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 considered as a good prognostic factor.



Immunohistochemical analyses of LPCs (proliferative or not), macrophages, and proliferative hepatocytes were performed on the admission biopsies of 68 patients with severe ASH who were recruited in 20 different centers in Belgium and France. Patients were first divided in two groups, improvers or non-improvers, according to the change in the MELD (Model For End-Stage Liver Disease) score at 3 months after baseline. They were further divided in two other groups, responders or non-responders to corticosteroids, according to the Lille score at Day 7. RESULTS In severe ASH, liver regeneration mechanisms are activated. In our population, we found that the total amount of LPCs was positively correlated with disease severity assessed by the MELD score at the time of screening. However, no significant differences in total LPCs, proliferative LPCs, proliferative hepatocytes, and macrophages were found between improvers and nonimprovers or between the favorable and unfavorable Lille score groups. No significant difference in survival (at 3 months or overall) was found either between high and low proliferators for hepatocytes or LPCs. Regarding cell populations, a higher number of macrophages was associated with an increased proliferation of both hepatocytes and LPCs. A higher hepatocyte proliferation was also correlated with a higher proliferative LPC count.



We did not identify hepatocyte proliferation, LPC proliferation, or macrophage expansion as prognostic factors in severe ASH. Macrophage expansion was correlated with an increased proliferation of hepatocytes and LPCs, with hepatocytes and LPCs proliferating simultaneously.