The role of neutrophils in alcohol-related hepatitis

Alcohol-related liver disease (ALD) is a major cause of liver disease associated mortality, with inpatient care being a major contributor to clinical and economic burden. Alcohol-related hepatitis (AH) is an acute inflammatory form of ALD. Severe AH is associated with a high short-term mortality, with infection being a common cause of death. The presence of AH is associated with increased numbers of circulating and hepatic neutrophils. We review the literature on the role of neutrophils in alcoholic hepatitis. In particular, we explain how neutrophils are recruited to the inflamed liver, and how their antimicrobial functions (chemotaxis, phagocytosis, oxidative burst, NETosis) may be altered in AH. We highlight evidence for the existence of ‘high-density’ and ‘low-density’ neutrophil subsets. We also describe the potentially beneficial roles of neutrophils in resolution of injury in AH through their effects on macrophage polarisation, and hepatic regeneration. Finally, we discuss how manipulation of neutrophil recruitment/function may be used as a therapeutic strategy in AH. For example, correction of gut dysbiosis in AH could help to prevent excess neutrophil activation, or treatments could aim to enhance miR-223 function in AH. The development of markers that can reliably distinguish neutrophil subsets, and the development of animal models that accurately reproduce human disease are important areas for facilitating translation of research in this important field.