A novel mechanism of abnormal hematological indices in liver cirrhosis: Bone marrow endothelial cell dysfunction caused by humoral inhibitor affects the hematopoietic function of bone marrow

Abnormal hematological indices (HIs), a complication of liver cirrhosis (LC), present difficulties in the treatment of LC and pose a serious threat to the survival of patients. LC is a dynamic wound-healing process that occurs in response to repeated liver injury and is a chronic disorder associated with changes in various organs and tissues. It has been reported that humoral inhibitor in the formation of LC could affect the hematogenic functions of bone marrow (BM) by acting on erythroid differentiation. This indicates that the BM microenvironment is affected by humoral inhibitor in LC. Bone marrow endothelial cells (BMECs) are very important components of the BM microenvironment that function as the cytoskeleton to support the adhesion of hematopoietic stem cells (HSCs). In addition, they can secrete cytokines, which have important functions in regulating positioning, homing, proliferation, differentiation and other functions of HSCs on the BM microenvironment. These functions of BMECs may be affected due to direct contact with blood and long-term exposure to an environment with humoral inhibitor in the presence of LC. Multiple studies have shown that during the formation of LC, hepatic sinusoid endothelial cells were damaged and secreted cytokines and matrix proteins. Moreover, these cytokines and matrix proteins were involved in the formation and development of LC. Similar in function to mature-stage BM, liver at the embryonic stage also functions as a type of hematogenic organ. With similar anatomical position and functions to that of hepatic sinusoid endothelial cells, BMECs may undergo similar changes and impair hematogenic function of BM. More importantly, we found even more convincing evidence in that the humoral inhibitor in LC could lead to the ultrastructural damage of BMECs that were positively related to the degree of severity of LC. Therefore, we hypothesise the existence of a novel mechanism for abnormal HIs in LC: the continuous humoral inhibitor may lead to abnormal cytokine secretion of BMECs and attenuate their supporting functions, and such alterations of BMECs may lead to BM microenvironment disorder and dysfunction of HSCs, finally causing abnormal HIs.