Age at the time of infection with hepatitis B virus (HBV) is the most important factor influencing chronicity. Of those infected with HBV during the perinatal (birth) period and infancy, 90% and 25%-30%, respectively, will develop chronic infection, whereas only 5-10% of those infected after age 5 will develop chronic infection. The natural history of HBV infection in infancy can generally be artificially divided into four phases, namely the immune tolerance phase, the immune clearance phase, the inactive or low (non) replication phase and the reactive phase. 1, immune tolerance phase: characterized by positive serum HBsAg and HBeAg, high HBV DNA load ( often > 106 IU/mL, equivalent to 107 copies/mL), but normal serum alanine aminotransferase (ALT) levels, no significant abnormalities in liver histology and can be maintained for years or even decades, or mild inflammatory necrosis, no or only slow progression of liver fibrosis. 2, immune clearance stage: manifested by serum HBV DNA titer > 2000 IU/mL (equivalent to 104 copies/mL), accompanied by continuous or intermittent elevation of ALT, moderate or severe inflammatory necrosis of liver histology, liver fibrosis can progress rapidly, some patients can develop into cirrhosis and liver failure. 3, inactive or low (non) replication stage: manifested by HBeAg negative, anti-HBe positive, HBV DNA persistently below 2000 IU/mL (equivalent to 104 copies/mL) or undetectable (PCR method), normal ALT levels, no inflammation or only mild inflammation in liver histology; this is the result of HBV infection gaining immune control, and most patients in this stage have cirrhosis and The risk of HCC is greatly reduced in some patients who have sustained HBV DNA conversion for several years, with a spontaneous HBsAg serological conversion rate of 1 to 3%/year. 4. Reactive phase: Some patients in the inactive phase may have one or several episodes of hepatitis, mostly HBeAg negative, anti-HBe positive (partly due to low or no HBeAg expression level caused by pre-C and/or BCP variants), but still have active HBV DNA replication, persistent or recurrent abnormal ALT, and become HBeAg negative chronic These patients can progress to liver fibrosis, cirrhosis, decompensated cirrhosis and HCC; some patients can also develop spontaneous HBsAg disappearance (with or without anti-HBs) and reduced or undetectable HBV DNA, thus the prognosis is often good. A small number of patients in this stage can return to HBeAg-positive status (especially in immunosuppressed states such as when receiving chemotherapy). Not all people infected with HBV go through these four stages. Only a minority (about 5%) of HBV infections in the neonatal period result in spontaneous clearance of HBV, while most have a long immune resistance period followed by an immune clearance period. However, most adolescents and adults infected with HBV during adolescence do not have an immune tolerance period but enter directly into the immune clearance phase, and most of them can clear HBV spontaneously (about 90%-95%), while a minority (about 5%-10%) develop HBeAg-positive chronic hepatitis B. Spontaneous HBeAg serologic conversion occurs mainly during the immune clearance phase, with an annual incidence of about 2%-15%, with a higher incidence in those younger than 40 years of age, with elevated ALT, and infected with HBV genotypes A and B. HBsAg clearance occurs in about 0.5%-1.0% per year after HBeAg serologic conversion. The incidence of cirrhosis in patients with chronic HBV infection is related to the infection status. Patients in the immune tolerance phase have only very mild or no progression of liver fibrosis, whereas the immune clearance phase is a period of high incidence of cirrhosis. The cumulative incidence of cirrhosis is positively correlated with persistently high viral load, and HBV DNA is a risk factor independent of HBeAg and ALT that can independently predict the development of cirrhosis. Risk factors for the development of cirrhosis also include alcoholism, co-infection with HCV, HDV or HIV. Primary hepatocellular carcinoma (HCC) is less likely to occur in non-cirrhotic patients. HBeAg positivity and/or HBV DNA > 2,000 IU/mL (equivalent to 104 copies/mL) are significant risk factors for the development of cirrhosis and HCC. Large sample studies have shown that older age, male gender, and high ALT levels are also risk factors for the development of cirrhosis and HCC. family history of HCC is also a relevant factor, but HBV viral load is more important in the same genetic background.