Hepatic encephalopathy is a common and serious complication of end-stage liver diseases such as liver cirrhosis， and it is basically a neuropsychiatric syndrome resulting from metabolic disorders caused by severe acute or chronic liver dysfunction or portosystemic shunt. In clinical practice， the onset of hepatic encephalopathy does not completely correlate linearly with the level of blood ammonia and is often triggered by extrahepatic factors， suggesting the presence of complex multiorgan crosstalk in the pathogenesis of hepatic encephalopathy. Based on the four main pathogeneses of ammonia toxicity， inflammation， neurotransmitter imbalance， and oxidative/nitrosative stress， this article systematically elaborates on the mechanism of multiorgan crosstalk in hepatic encephalopathy and discusses the emerging risk factors such as sarcopenia and diabetes mellitus， in order to provide a novel theoretical framework for deepening the understanding of the pathophysiological mechanisms of hepatic encephalopathy and formulating clinical diagnosis and treatment strategies in the future.