Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Abstract

Background:The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear.Objectives:The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF.Patients and Methods:Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ≥ 20 ULN, total bilirubin ≥ 5 ULN, 40% < prothrombin time activity ≤ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method.Results:IL-4, IL-12p70 and IFN-γ were undetectable; IL-1β, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001).Conclusions:The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF.

Plasma interleukin‐10 predicts short‐term mortality of acute‐on‐chronic hepatitis B liver failure

“…Furthermore, we also reported that nonsurvivals showed higher plasma IL‐10 level compared with survivals, and IL‐10 correlated with mortality of ACHBLF patients. These results were agreeable with previous studies . In the patients with liver failure, IL‐10 might impair the production of monocyte pro‐inflammatory cytokines and lead to the dysfunction of immune response .…”

Up‐regulation of A20 gene expression in peripheral blood mononuclear cells is associated with acute‐on‐chronic hepatitis B liver failure

“…Based on the above results, we focused on the role of A20 in the pathogenesis of ACHBLF. A number of studies have shown that the immune‐inflammatory cytokines in the prophase or early phase of ACHBLF correspond to a high‐expression status, suggesting that cytokines play an important factor in the development of ACHBLF . Similarly, our present study showed elevated levels of several pro‐ and anti‐inflammatory cytokines in ACHBLF including IL‐1 β , IL‐6 and IL‐10.…”

“…Inflammatory cytokines IL‐1 β , IL‐6 and IL‐10 play crucial roles in ACHBLF pathogenesis . To evaluate the relationships between A20 expression and plasma levels of pro‐ or anti‐inflammatory mediators in patients with ACHBLF, we examined plasma concentrations of IL‐1 β , IL‐6 and IL‐10 (Fig.…”

“…The crucial role of A20 was clearly demonstrated with the generation of A20 knockout (A20 −/− ) mice, which display severe inflammation and tissue damage in multiple organs causing premature death . Some studies have demonstrated that several inflammatory cytokines, such as IL‐1 β , IL‐6 and IL‐10, may be involved in the development of liver failure . In addition, A20‐silenced dendritic cells (DCs) have an enhanced T‐cell stimulatory capacity to skew naive CD4 + T cells towards a T‐helper (Th) 1 phenotype, but not cells of regulatory T cells (Tregs), Th2, or Th17 phenotype in in vitro stimulations .…”

Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis

“…Different markers and prognostic scores have been tested on their ability to stratify the risk of mortality in patients with compensated or decompensated liver cirrhosis as well as in patients with acute-on-chronic liver failure (ACLF). So far, biomarkers of systemic inflammation and infection have performed fairly well to distinguish patients with a stable disease course from those at higher risk of decompensation [2][3][4]. Moreover, biomarkers of macrophage activation and immune danger signals were demonstrated to predict outcome in patients with decompensated liver cirrhosis, especially in patients with alcoholic hepatitis [5].…”