amatoxin and Hepatic-Encephalopathy

Topics: Acute Disease; Adult; Aged; Amanitins; Female; Glasgow Coma Scale; Hepatic Encephalopathy; Hong Kong; Humans; Liver Transplantation; Male; Middle Aged; Mushroom Poisoning

Topics: Acetylcysteine; Adult; Amanita; Amanitins; Cause of Death; Combined Modality Therapy; Critical Care; Diagnosis, Differential; Hepatic Encephalopathy; Humans; Liver Function Tests; Liver Transplantation; Male; Mushroom Poisoning; Prognosis; Silybin; Silymarin

Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.

Topics: Alanine Transaminase; Amanitins; Animals; Aspartate Aminotransferases; Cytokines; Disease Progression; Gene Expression; Hepatic Encephalopathy; Interleukin-6; L-Lactate Dehydrogenase; Lipopolysaccharides; Liver Failure, Acute; Liver Function Tests; Macaca mulatta; Mice; Monocytes