Liver Disease

BACKGROUND: Hepatitis B virus (HBV) is an infectious disease with unfavorable consequence for patients and involved in chronic inflammation of liver. The present study aimed to investigate whether High-mobility group protein B (HMGB)1/NF-kB aggravates inflammation enhancing the expression of interleukin (IL)-23.

METHODS: Baseline serum HMGB1, IL-6, IL-12, IL-17, IL-23, TNF-α, and IFN-γ was analyzed using from inactive HBsAg carrier state (IC), chronic hepatitis B (CHB), HBV-related acute-on-chronic liver failure (HBV-ACLF) patients and healthy individuals who served as healthy controls (HCs). Purified monocytes were isolated from peripheral blood and induced into monocyte-derived dendritic cells (MoDCs), HMGB1, NF-κB, IL-23 and IL-23R expression in MoDCs from 4 groups was analyzed using real-time PCR and flow cytometric analysis. HMGB1, HBsAg, HBeAg and HBcAg in vitro stimulate MoDCs. The siRNA against NF-κB and overexpression of NF-κB was utilized to assess the impact of NF-κB on pro-inflammatory properties.

RESULTS: Baseline serum HMGB1 and IL-23 were significantly upregulated in non-survival compared with survival of HBV-ACLF patients. Serum HMGB1 and IL-23 downregulated in survival after treatment, whereas even upregulated in non-survival of HBV-ACLF patients. HMGB1, HBsAg, HBeAg and HBcAg in vitro stimulation induced the expression of NF-Kb and IL-23 in MoDCs of HCs. On the other hands, nuclear factor-kappa B regulated the expression of IL-23 in monocyte-derived dendritic cells of HBV-ACLF patients.

CONCLUSIONS: High baseline serum HMGB1 and IL-23 are associated with HBV-ACLF patient mortality. HMGB1/NF-KB contribute to the inflammation enhancing the expression of IL-23 by MoDCs, which mediates damage-induced liver inflammation in HBV-ACLF patients .

Posted by: Suxia Bao, doctoral candidate, Huashan Hospital, Fudan University, China (03-Nov-2016)