Age at the time of infection is the most important factor affecting chronicity. Among those infected with HBV during the perinatal (birth) period and infancy, 90% and 25%-30%, respectively, will develop chronic infection, while 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. Immunotolerant 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 inflammation, necrosis, and no or slow progression of liver fibrosis. Immunoclearance phase: manifested by serum HBV DNA titers > 2000 IU/ml (equivalent to 104 copies/ml), accompanied by persistent or intermittent elevation of ALT/aspartate aminotransferase (AST), liver histology – moderate or severe inflammation, necrosis, liver fibrosis can progress rapidly, and some patients can develop cirrhosis and liver failure. Inactive or low (non) replication phase: manifested by HBeAg negative, anti-HBe positive, HBV DNA consistently below 2000 IU/ml (equivalent to 104 copies/ml) or undetectable (PCR method), normal ALT levels, and no or only mild inflammation of liver histology; this is the result of immune control of HBV infection, and most patients in this phase have a greatly reduced risk of cirrhosis and The risk of cirrhosis and HCC is greatly reduced in most patients in this stage, and in some patients who have sustained HBV DNA conversion for several years, the spontaneous HBsAg serological conversion rate is 1-3%/year; a small proportion of patients in this stage can return to HBeAg-positive status (especially in the immunosuppressed state such as when receiving chemotherapy). Immunu reactive phase: Some patients in the inactive phase may have one or more episodes of hepatitis, mostly HBeAg negative, anti-HBe positive (due to low or no expression of HBeAg in the pre-C region and/or BCP variants), but still have active replication of HBV DNA and persistent or recurrent abnormal ALT, becoming HBeAg negative CHB, 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. Not all people infected with HBV go through the above 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 period of immune resistance followed by an immune clearance phase, an inactive phase, and, in a few cases, a reactive phase. However, most adolescents and adults infected with HBV during adolescence have no immune tolerance period and go directly to the immune clearance phase, most of them can spontaneously clear HBV (about 90-95%), while a few (about 5-10%) develop HBeAg-positive chronic hepatitis B. Spontaneous HBeAg serologic conversion occurs mainly during the immune clearance period, 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. 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.