High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure

Tang

et al. 2021

Front. Mol. Biosci.

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

Section: Cytokines In Hepatitis B Virus Infectionmentioning

confidence: 99%

Cytokines and Chemokines in HBV Infection

Zhong

Tang

et al. 2021

Front. Mol. Biosci.

“…Additionally, PAB may re ect the pathological process of ACLF to some extent. Previous studies have shown that uncontrolled in ammatory responses and immunological dysfunction play important roles in pathogenesis, which also affects the prognosis of ACLF [21]. Numerous cytokines, such as IL-6, were synthesized in response to in ammation, resulting in decreased synthesis and low serum concentrations of these proteins, including PAB [22].…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic model based on Prealbumin for predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure

Wang

Jin

et al. 2022

Preprint

Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a clinical syndrome associated with a high short-term mortality rate, and accurate clinical decision-making requires an accurate assessment of prognosis. The purpose of this study was to develop a simple and effective prognostic model for predicting short -term mortality in HBV-ACLF patients. Methods We retrospectively enrolled 170 patients to develop and validate a novel prognostic model for predicting 30-day mortality in HBV-ACLF patients. Using univariate and multivariate logistic regression analysis, laboratory and clinical data were obtained to identify independent predictors of short-term mortality. Results We found the Prealbumin (PAB) level at admission was a strong independent predictor for 30-day mortality, with an AUROC of 0.760. The HIAPP score, a prognostic-score model based on five independent prognostic variables, including PAB, Platelet (PLT), international normalized ratio (INR), the occurrence of hepatic encephalopathy (HE), and age, was markedly lower in survivors than in non-survivors (-2.80 ± 0.21 vs 0.97 ± 0.41, P < 0.001). Additionally, the HIAPP score was positively and strongly correlated with the CLIF‐SOFA, MELD, and CLIF‐C ACLF scores. The AUROC value for the HIAPP score was 0.899, which was found to be superior to the MELD (AUROC = 0.795), CLIF‐SOFA (AUROC = 0.731), and CLIF‐C ACLF (AUROC = 0.700) scores for 30‐day mortality. These findings were validated using a validation cohort. Conclusion PAB is a simple and useful predictive index for 30‐day mortality in HBV-ACLF. The HIAPP score was found to be an easy-to-use pragmatic prognostic score and superior to the CLIF‐SOFA, MELD, and CLIF‐C ACLF scores.

“…Studies have found that the IL-6 level of patients with HBV-ACLF rapidly progressing to death is higher than that of patients with survival, and IL-6 is an independent factor affecting the prognosis of HBV-ACLF. HBV-ACLF patients with high IL-6 levels have more than twice the risk of death compared to patients with low IL-6 levels [ 36 ]. However, it has been suggested that acute and only short-term increases in IL-6 levels may benefit liver regeneration, while chronic increases in IL-6 may adversely affect the liver and other organs.…”

Section: Interleukin-6mentioning

confidence: 99%

“…The complex function of IL-6 involves hepatic quasi- or transsignaling [ 37 – 39 ]. It can be seen that IL-6 level and duration simultaneously influence the development of HBV-ACLF [ 36 ].…”

Section: Interleukin-6mentioning

confidence: 99%

See 1 more Smart Citation

Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure

Mediators of Inflammation

Gou

et al. 2022

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.