The way is simple： A brief natural history of chronic hepatitis B virus infection and disease progression

Chronic hepatitis B virus （HBV） infection is the major cause of chronic hepatitis B （CHB）， liver cirrhosis， and primary hepatocellular carcinoma （HCC） and brings huge health and economic burdens to the society. The disease progression of CHB is driven by the interaction between the virus， host immune response， and infected hepatocytes. Staging of the natural history of chronic HBV infection will help to understand disease progression， assess the stage of disease progression， and provide guidance for determining the time and regimen of antiviral therapy. Due to the controversy over the existence of a true immune tolerance phase， Guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） in China weakens the association between disease state and host immune status and provides an updated description of the natural history of chronic HBV infection based on the four disease stages from the 2017 European Association for the Study of the Liver （EASL） guidelines， i.e.， HBeAg-positive chronic HBV infection， HBeAg-positive CHB， HBeAg-negative chronic HBV infection， and HBeAg-negative CHB. Moreover， it fails to fully resolve the issue of the “indeterminate phase”. With the growing trend of expanding antiviral treatment strategies in clinical practice， the current staging system based on natural history can hardly meet clinical needs， and thus it is necessary to make updates. This article elaborates on the discovery of the natural history of chronic HBV infection， the problems of the existing staging system of natural history， and related recommendations， in order to simplify the staging system of natural history， align with current antiviral treatment regimens， and facilitate clinical decision-making by clinicians.