Lejeune Adrienne, Stärkel Peter, Louvet Alexandre, Hittelet Axel, Bazille Céline, Bastens Boris, Orlent Hans, Lasser Luc, Dekoninck Xavier, Negrin Dastis Sergio, Delwaide Jean, Geerts Anja, Moreno Christophe, de Galocsy Chantal, Putzeys Virginie, Langlet Phillippe, Reynaert Hendrik, Francque Sven, Komuta Mina, Lanthier Nicolas
Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
Transl Gastroenterol Hepatol. 2025 Jan 17;10:3. doi: 10.21037/tgh-24-92. eCollection 2025.
Keratin 7 positive (K7) cells are considered to be activated in case of impaired hepatocyte replication. Their exact role and their interaction with hepatocytes and macrophages also implicated in liver regeneration remain poorly characterized in humans. The aim of this study is to evaluate hepatocyte, K7 cells and macrophage populations in severe alcohol-related steatohepatitis (sASH) and to link them with liver injury and patients' outcomes.
Immunohistochemical and morphometric studies for total K7 cells, macrophages (CD68 cells), proliferative hepatocytes (Ki67 hepatocytes) and proliferative K7 cells (double K7 and Ki67) were performed on liver biopsies of patients with sASH recruited prospectively in 16 different centres. Patients were divided into improvers or non-improvers, according to mortality and model for end-stage liver disease (MELD) score change at 3 months.
Fifty-seven cases were included for histological and morphometrical assessment. Liver total K7 cell expansion was positively correlated to the severity of the disease evaluated by the MELD score. A proportion of these K7 cells were proliferating. The number of proliferating K7 cells was less than the number of proliferating hepatocytes. Increased hepatocyte replication was correlated to a higher proliferative K7 cell count. A higher number of macrophages was associated with a higher proliferation of both hepatocytes and K7 cells. No difference of total K7 cells, proliferative K7 cells, proliferative hepatocytes or macrophages was observed between improvers and non-improvers.
In biopsy-proven cases of sASH, proliferation of hepatocytes and K7 cells occurs in parallel. This could suggest that liver progenitor cells begin to replicate even in the absence of massive hepatocyte senescence in humans, or that proliferating progenitor cells are capable of giving rise to hepatocytes with replicative skills. This is associated with macrophagic expansion, which is therefore considered beneficial. However, in this severe, life-threatening disease, these mechanisms remain insufficient to improve patient prognosis.
在肝细胞复制受损的情况下，角蛋白7阳性（K7）细胞被认为处于激活状态。在人类中，它们的确切作用以及它们与肝细胞和巨噬细胞的相互作用（这也与肝再生有关）仍未得到充分描述。本研究的目的是评估严重酒精性脂肪性肝炎（sASH）中的肝细胞、K7细胞和巨噬细胞群体，并将它们与肝损伤及患者预后联系起来。
对前瞻性招募自16个不同中心的sASH患者的肝活检组织进行免疫组织化学和形态计量学研究，检测总K7细胞、巨噬细胞（CD68细胞）、增殖性肝细胞（Ki67肝细胞）和增殖性K7细胞（K7和Ki67双阳性）。根据3个月时的死亡率和终末期肝病模型（MELD）评分变化，将患者分为病情改善者或未改善者。
纳入57例进行组织学和形态计量学评估。肝脏总K7细胞扩张与通过MELD评分评估的疾病严重程度呈正相关。这些K7细胞中有一部分在增殖。增殖性K7细胞的数量少于增殖性肝细胞的数量。肝细胞复制增加与增殖性K7细胞计数较高相关。巨噬细胞数量增加与肝细胞和K7细胞的增殖增加相关。在病情改善者和未改善者之间，未观察到总K7细胞、增殖性K7细胞、增殖性肝细胞或巨噬细胞的差异。
在经活检证实的sASH病例中，肝细胞和K7细胞的增殖同时发生。这可能表明，即使在人类不存在大量肝细胞衰老的情况下，肝祖细胞也开始复制，或者增殖的祖细胞能够产生具有复制能力的肝细胞。这与巨噬细胞扩张有关，因此被认为是有益的。然而，在这种严重的、危及生命的疾病中，这些机制仍不足以改善患者的预后。
