DLL4-Notch signalling in acute-on-chronic liver failure: State of the art and perspectives.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with multiple-organ failures and high short-term mortality. Acute insults to patients with chronic liver disease can lead to ACLF, among which, hepatitis B virus-related ACLF is the most common type of liver failure in the Asia-Pacific region. Currently, immune-metabolism disorders and systemic inflammation are proposed to be the main mechanisms of ACLF. The resulting cholestasis and intrahepatic microcirculatory dysfunction accelerate the development of ACLF. Treatments targeting immune regulation, metabolic balance, microcirculation maintenance and bile duct repair can alleviate inflammation and restore the tissue structure. An increasing number of studies have demonstrated that delta-like ligand 4 (DLL4), one of the Notch signalling ligands, plays a vital role in immune regulation, metabolism, angiogenesis, and biliary regeneration, which participate in liver pathological and physiological processes. The detailed mechanism of the DLL4-Notch signalling pathway in ACLF has rarely been investigated. Here, we review the evidence showing that DLL4-Notch signalling is involved in ACLF and analyse the potential role of DLL4 in the treatment of ACLF.