Abstract
Alcoholic liver disease (ALD) encompasses a spectrum of liver injury ranging from steatosis to steatohepatitis, fibrosis, and finally cirrhosis. Accumulating evidences have demonstrated that Kupffer cells (KCs) play critical roles in the pathogenesis of both chronic and acute ALD. It has become clear that alcohol exposure can result in increased hepatic translocation of gut-sourced endotoxin/lipopolysaccharide, which is a strong M1 polarization inducer of KCs. The activated KCs then produce a large amount of reactive oxygen species (ROS), pro-inflammatory cytokines, and chemokines, which finally lead to liver injury. The critical roles of KCs and related inflammatory cascade in the pathogenesis of ALD make it a promising target in pharmaceutical drug developments for ALD treatment. Several drugs (such as rifaximin, pentoxifylline, and infliximab) have been evaluated or are under evaluation for ALD treatment in randomized clinical trials. Furthermore, screening pharmacological regulators for KCs toward M2 polarization may provide additional therapeutic agents. The combination of these potentially therapeutic drugs with hepatoprotective agents (such as zinc, melatonin, and silymarin) may bring encouraging results.
Highlights
Alcoholic liver disease (ALD) remains one of the predominant causes of liver-related morbidity and mortality worldwide [1]
A recently published multicenter, doubleblind, randomized trials with a 2-by-2 factorial design showed that pentoxifylline did not improve survival of alcoholic hepatitis (AH) patients [160]. Due to these conflicting results, several meta-analyses have been performed, and the results showed that pentoxifylline could not improve the short-term survival of AH patients compared with placebo; combination of pentoxifylline and corticosteroid could reduce the incidences of hepatorenal syndrome and the infection risk compared with corticosteroid therapy alone [161,162,163]
Kupffer cells (KCs) are activated in both chronic and acute ALD, which is driven by gut-sourced endotoxin/LPS
Summary
Alcoholic liver disease (ALD) remains one of the predominant causes of liver-related morbidity and mortality worldwide [1]. Kupffer Cells and Alcoholic Liver Disease and non-parenchymal cells in the liver are involved in the pathogenesis of ALD. Accumulating evidence suggests that Kupffer cells (KCs), the resident macrophages in the liver, play crucial roles [4,5,6]. KCs originate from bone narrow-derived monocytes and account for about 20–25% of non-parenchymal cells in the liver [7]. KCs play key roles in host defense by removing foreign, toxic and infective substances from the portal blood and have been demonstrated to be involved in the pathogenesis of many kinds of liver diseases [8, 9]. We discuss the critical roles of KCs in the pathogenesis of both chronic and acute ALD, KCs polarization in ALD, and potential therapeutic targets for ALD treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
