Impaired adaptive immunity is an early event in liver cirrhosis preceding acute-on-chronic liver failure

Objective:

Acute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of the innate immune system. In contrast, little is known about changes of the adaptive immune system in ACLF.

Methods:

Patients with compensated liver cirrhosis, decompensated liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping of relevant innate and adaptive immune cell populations was performed using high dimensional flow cytometry. In addition, replication of Torque teno (TT) virus as a marker of immunosuppression was quantified in serum.

Results:

A high frequency of detectable TT virus was observed already in patients with compensated liver cirrhosis compared to healthy controls (> 50% vs. 19%, P = 0.0003), suggesting early occurrence of immunosuppression in the course of liver cirrhosis. In line, profoundly impaired cellular immune responses were observed, deduced by reduced numbers of important cell populations of the adaptive and innate immune system like CD4+ T cells, CD8+ T cells, B cells, NK cells, and dendritic cells. Importantly, most of the observed changes were already evident in patients with compensated liver cirrhosis and were fully developed in patients with acutely decompensated liver cirrhosis, while ACLF was associated with only few additional changes in immune cell frequencies like a diminished compartment of Vδ2 γδ T cells.

Conclusion:

Impaired innate and – in particular – adaptive cellular immunity occurs early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis.