Mononuclear myeloid-derived suppressor cells expansion is associated with progression of liver failure in patients with acute decompensation of cirrhosis

Abstract

Patients with acute decompensation (AD) of cirrhosis have different clinical courses. Immune dysfunction affects disease outcomes. The profile of myeloid-derived suppressor cells (MDSCs), polymorphonuclear- (PMN-MDSCs) and mononuclear- (M-MDSCs) subsets in AD and their associations with different clinical courses are still unclear. This study included 36 healthy controls (HC), 20 patients with compensated cirrhosis (CC) and 107 patients with AD. Based on the condition at enrollment and 90 days of follow-up, the patients with AD were divided into AD-acute-on-chronic liver failure (AD-ACLF), stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC) and pre-acute-on-chronic liver failure (Pre-ACLF) groups. The percentages of MDSCs, PMN-MDSCs, and M-MDSCs in the peripheral blood of patients with AD were significantly higher than those in HC and CC. Lactate levels, Child-Pugh score, and MDSCs were risk factors for the occurrence of AD. A positive correlation exists between MDSCs and indices of systemic inflammation and liver failure. In the AD cohort, the percentages of M-MDSCs in the Pre-ACLF and AD-ACLF groups were significantly higher than those in the UDC and SDC groups. The percentages of MDSCs and PMN-MDSCs in the AD groups increased; however, the difference was not statistically significant. MDSCs and M-MDSCs positively correlated with the incidence of liver failure. Sex, alcoholic etiology, bacterial infection, and M-MDSCs were independent risk factors for liver failure in patients with AD. Our data indicate that M-MDSCs expansion, rather than PMN-MDSCs expansion, might predict poor prognosis in patients with AD. Reducing the suppressive activity and number of MDSCs and M-MDSCs are promising strategies for immunotherapy in patients with AD.

Keywords: Acute decompensation; Acute-on-chronic liver failure; Mononuclear myeloid-derived suppressor cells; Myeloid-derived suppressor cells; Polymorphonuclear myeloid-derived suppressor cells.