Objective To observe the incidence of spontaneous clearance of hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB) patients ,and to investigate the related factors of the spontaneous clearance of HBV DNA and to determine the time to start antiviral therapy .Methods Patients who met the inclusion criteria were recruited from the follow-up cohort of chronic HBV infection from January 2008 to August 2017 for observation .The liver function including alanine aminotransferase (ALT) levels ,HBV DNA load and serum markers of HBV were measured at baseline ,month 1 ,month 3 and month 6 of follow-up . Evaluation index included cumulative HBV DNA negative conversion rate and cumulative HBeAg negative conversion rate .Multivariable analysis was used to analyze the factors associated with the spontaneous clearance of HBV DNA .Results A total of 116 patients were recruited in this study .All the patients showed ALT level elevation at baseline .Without antiviral treatment ,the cumulative HBV DNA negative conversion rate was 12 .9％ after 6-month observation .HBeAg negative conversion rate was 22 .5％ .Multivariable analysis showed that patients without a family history of HBV infection ,baseline ALT level >3 times the upper limit of normal (ULN) and HBV DNA level <6 lg copies/mL had higher cumulative HBV DNA spontaneous clearance rate .HBV DNA negative conversion rate in patients whomet all the above three conditions was up to 75％ .Conclusions In CHB patients and ALT level elevation for the first time , some patients could achieve spontaneous clearance of HBV DNA without antiviral therapy .Patients without a family history of HBV infection ,baseline ALT level >3 ULN and HBV DNA level <6 lg copies/mL have higher rate of cumulative HBV DNA spontaneous clearance .

Objective:To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs).Methods:The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The 2 test was used for rate comparison. Results:The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion:The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.