Deregulation of Regulatory T Cells in Acute-on-Chronic Liver Failure: A Rat Model

Abstract

Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

NACSELD acute‐on‐chronic liver failure (NACSELD‐ACLF) score predicts 30‐day survival in hospitalized patients with cirrhosis

“…WBC count remains a critical marker of prognosis; greater inflammation, as evidenced by a higher WBC count, is associated with worse outcomes. Current data have documented that an excessive immunologic response is part of ACLF initiation . However, the innate and adaptive immune response in the infected versus uninfected patient with ACLF needs further exploration.…”

“…Current data have documented that an excessive immunologic response is part of ACLF initiation. (26,27) However, the innate and adaptive immune response in the infected versus uninfected patient with ACLF needs further exploration. In addition, understanding the evolution of these responses over time and their role in predisposing patients to second infections requires urgent evaluation to develop intervention strategies that will improve outcomes.…”

Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

“…Additionally, in the previously mentioned reports, a Th17/Treg axis imbalance that could have a role in the development of ALF in CHB has been observed. Nevertheless, as well as the studies related to IL-10, the results are diverse; in some studies, it was found a higher frequency of Th17 cells in ACLF, whereas others did not find significant changes in Treg cells [ 136 , 137 , 138 , 139 ].…”

The Role of Prophylactic Antibiotics In Hepatitis B Virus-Related Acute-On-Chronic Liver Failure Patients: A Retrospective Study

“…ACLF is an acute deterioration of chronic liver disease characterized by multiple organ failure and high short-term mortality, with 3-month and 1-year mortality rates being 53.7% and 67.4%, respectively (22). ACLF patients are highly susceptible to BIs because these patients display sepsis-like immune paralysis (23)(24)(25).…”