Bile and circulating HMGB1 contributes to systemic inflammation in obstructive jaundice

Obstructive jaundice (OJ) patients with cholangitis are prone to sepsis; however, the underlying mechanisms are still not clear and need to be clarified.

Analyzing all available published data related to the title of this article.

OJ leads to absence of gut luminal bile and accumulation of hepatic and circulating bile acids. Absence of gut luminal bile deprives the gut from its antiinflammatory, endotoxin-binding, bacteriostatic, mucosal-trophic, epithelial tight-junction maintaining, and gut motility-regulating effects, leading to gut bacterial overgrowth, mucosal atrophy, mucosal tight-junction loss, and gut motility dysfunction. These alterations promote intestinal endotoxin and bacterial translocation (BT) into portal and systemic circulation. Gut BT triggers systemic inflammation, which can lead to multiple organ dysfunctions in OJ. The accumulation of hepatic and circulating bile acids kills/damages hepatocyte and Kupffer cells, and it also significantly decreases the number of liver natural killer T-cells in OJ. This results in impaired hepatic and systemic immune function, which facilitates BT. In addition, neutralizing bile HMGB1 can reverse endotoxemic bile-induced gut BT and mucosal injury in mice, suggesting that bile HMGB1 in OJ patients can be responsible for internal drainage-related clinical complications. Moreover, the elevated circulating HMGB1 level may contribute to multiple organ injuries, and it might also mediate gut BT in OJ.

HMGB1 may significantly contribute to systemic inflammation and multiple organ dysfunctions in OJ.