Objective To investigate the serum anti-HBc level in patients with different natural history of chronic hepatitis B virus (HBV) infection and cirrhosis,and its clinical value for distinguishing the natural history statue.Methods A total of 160 patients with chronic HBV infection from March 2015 to June 2016 were enrolled,and they were divided into immune tolerance group (n=43),HBeAg-positive chronic hepatitis B (CHB) group (n=37),inactive carrier group (n=39) and HBeAg-negative CHB group (n=41).A total of 44 patients with HBeAg-positive cirrhosis and 46 patients with HBeAg-negative cirrhosis were enrolled too.The general conditions data were collected,and HBsAg,HBeAg,anti-HBc,HBV DNA load and HBV genotype were detected.The associations between anti-HBc level and clinical parameters were analyzed,and the diagnostic value of anti-HBc for distinguishing different natural histories was analyzed.Results The anti-HBc levels in different natural history from high to low were as following: HBeAg-positive CHB group (4.22±0.68)log10 IU/mL,HBeAg-negative CHB group (3.89±0.88)log10 IU/mL,inactive carrier group (3.07±0.68)log10 IU/mL and immune tolerance group (2.88±0.82)log10 IU/mL.The anti-HBc levels in HBeAg-positive and HBeAg-negative cirrhosis patients were (3.04±0.82) and (3.15±0.86) log10 IU/mL,respectively.In HBeAg-positive CHB group,the anti-HBc was positively associated with ALT (r=0.353,P=0.032) and AST (r=0.421,P=0.009).In HBeAg-negative CHB group,the anti-HBc was positively associated with HBV DNA (r=0.343,P=0.028),ALT (r=0.458,P=0.003) and AST (r=0.495,P=0.001).The AUC of anti-HBc used to distinguish immune tolerance from HBeAg-positive CHB was 0.903,and the AUC used to distinguish inactive carrier from HBeAg-negative CHB was 0.833.Conclusion Anti-HBc levels in different natural history of chronic HBV infection are significantly different,and anti-HBc could be used to distinguish the natural history statue of chronic HBV infection with a higher diagnostic value than HBsAg.