Clinical research on antiviral treatment of chronic hepatitis B has gone through a history of more than 10 years, especially since it was marketed and applied to the clinical treatment of chronic hepatitis B. The treatment and efficacy of interferon against hepatitis B virus, represented by pegylated interferon alpha 2a, has made great progress and continuously improved the concept of chronic hepatitis B treatment, which is of milestone significance, improving the initial HB V DNA response, to In particular, the concept of durable immune control has been proposed, which sets a clear goal for the antiviral treatment of chronic hepatitis B. Durable immune control means that after treatment with interferon, even after stopping treatment, the body’s immune response can still be maintained. If the patient’s immunity can further continue to clear the virally infected cells, the patient can eventually be clinically cured. Differences in clearance of virally infected hepatocytes in interferon therapy: The efficacy of interferon antiviral therapy for chronic hepatitis B depends on host immune function. Due to differences in patients’ genetic background, immune status and viruses, there are differences in the rate of clearance of serum HBV, the rate of clearance of virally infected hepatocytes and the half-life of HBV cccDNA during interferon therapy, and even the differences are very significant, therefore , whether each patient can achieve immune control by interferon therapy or the time required to achieve immune control varies. One study showed that the half-life of HBV in the blood of HBeAg-positive HBV-infected patients in the natural state of infection ranged from 4 to 224 minutes (mean 46 minutes), while in HBeAg-negative patients treated with pegylated interferon a-2b in combination with lamivudine, the half-life of free virus in the blood ranged from 2.4 to 69.2 hours and the half-life of virally infected cells ranged from 2.5 to 75 days, while in recovery of acute HBV hepatitis in orangutans, the half-life of HBV cccDNA was 0.6 to 8 days. This shows that there is a difference of 10 to 20 being in the time to achieve immune control with interferon therapy in patients with chronic hepatitis B. To pursue higher therapeutic goals, extended interferon therapy is needed: The results of numerous clinical studies have shown that patients with durable immune control (HBeAg serologic conversion based on sustained suppression of viral replication and disappearance of HBsAg) can significantly reduce the incidence of cirrhosis and hepatocellular carcinoma, improve quality of life and prolong survival, and the results of long-term cohort studies of patients with chronic HBV infection have shown that the only treatment that gives The disappearance of HBsAg is considered a “clinical cure” and is the ultimate goal of antiviral therapy for chronic hepatitis B. The disappearance of HBsAg is the only indicator of good long-term outcome for individuals with chronic HBV infection. Immune control after interferon therapy is based on the clearance of virally infected hepatocytes to a certain level by interferon therapy and the continued inhibition of viral replication and further clearance of infected cells after cessation of therapy. Immune control and its achievement consists of three levels: 1) there must be a sustained viral response in both HBeAg-positive and negative patients; 2) there must be durable HBeAg serologic conversion in HBeAg-positive patients; and 3) the ideal endpoint of treatment is the disappearance of HBsAg or serologic conversion in both HBeAg-positive and negative patients. Of these three levels, for the vast majority of patients, the clinical pursuit of HBeAg serological conversion and HBsAg disappearance/serological conversion is most important because it is the amount of HBV cccDNA within the hepatocyte that determines the HBeAg and HBsAg levels, and the serum HBsAg level is significantly correlated with the HBV cccDNA level in the liver. The negative serum HBV DNA conversion and HBeAg serological conversion box HBsAg disappearance during interferon therapy are achieved gradually, and higher goals should be continuously pursued during treatment according to the patient’s efficacy. The results of numerous studies in clinical practice have shown that in HBeAg-positive chronic hepatitis B, prolonging the course of treatment can significantly improve HBeAg serological conversion and HBsAg disappearance rate. The result was that the incidence of HBeAg seroconversion in those who stopped treatment was 12%, while the rate of obtaining HBeAg seroconversion up to 32 weeks of treatment was 28%, and the rate of HBeAg conversion up to 32 weeks of treatment was 52% for those whose HBV DNA load dropped to 10 pg/ml at 16 weeks of treatment. The Zhu YY study compared the efficacy of pegylated interferon alpha-2a in the treatment of HBeAg-positive chronic hepatitis B patients at 48 and 72 weeks, and showed that the HBeAg seroconversion and HBsAg disappearance rates were 57.6% and 36.4%, respectively, in patients treated for 72 weeks, which were significantly higher than those treated for 48 weeks (HBeAg seroconversion and HBsAg disappearance rates Zhu and colleagues divided HBeAg-positive patients who had reached 105 copies/ml or less at 48 weeks of pegylated interferon alpha-2a treatment but did not develop HBeAg into two groups, one group continued treatment for 24 weeks and the other group stopped treatment. The results showed that the HBeAg seroconversion rate was 31% and the HBsAg disappearance rate was 19% in patients who continued treatment until 72 weeks, but in those who stopped treatment, no patients had HBeAg seroconversion and HBsAg disappearance at 72 weeks, indicating that patients who had only HBV DNA response at 48 weeks of treatment but did not obtain HBeAg serology should be extended. In patients with HBeAg-negative chronic hepatitis B, Chen et al. extended pegylated interferon alpha-2a therapy to 72 weeks, which increased the sustained viral response rate from 63.3% to 88.9% at 48 weeks and the HBsAg disappearance rate from 13.3% to 30.6%, again indicating that extended therapy significantly improved the outcome of HBeAg-negative patients. chronic hepatitis B patients. In patients with refractory genotype D HBeAg-negative chronic hepatitis B, extending the treatment course from 48 to 96 weeks of treatment increased the sustained viral response rate from 12% to 29% at 1 year post-discontinuation, and HBsAg disappearance was achieved in 6% of patients. In an extended treatment study of pegylated interferon alpha-2a in combination with nucleoside (acid) analogs for HBeAg-positive patients, Cao et al. showed that the rate of HBsAg disappearance at 96 weeks was significantly higher than that of patients treated for 48 weeks in either combination with adefovir or lamivudine. All of these results suggest that in both HBeAg-positive and negative patients, extending the duration of interferon treatment in pegylated interferon alpha-2a-based antiviral therapy can significantly improve patient outcomes, whether evaluated in terms of improved sustained viral response rate, improved HBeAg serologic conversion, or HBsAg disappearance rate. Good responders, in pursuit of higher therapeutic goals, should be more prolonged: For who needs to extend the course of treatment may be a more important issue in clinical practice, in previous studies, changes in indicators during treatment, especially changes in HBsAg levels can predict the acquisition of sustained viral response, HBeAg serology or HBsAg disappearance after treatment, while poor responders in treatment have difficulty in achieving immune control, timely changes in treatment regimen are advocated. Although the magnitude of the decrease in HBsAg levels on treatment predicts the acquisition of sustained immune control, it is only predicted over a fixed period of treatment time, which is not always the case in clinical practice, and many patients fail to achieve treatment despite a better response at 48 weeks of treatment, for whom there is a greater need for extended treatment. In a study by Ming-Hui Li and colleagues, extended treatment was performed in patients with chronic hepatitis B treated with pegylated interferon alpha-2a for 48 weeks and with HBsAg levels reaching <200 IU/ml to observe the rate of HBsAg disappearance, and the results showed that among all 217 treated patients, 13.4% (29) achieved HBsAg disappearance/HBsAg serological conversion,treatment time 75.4±42.8 weeks, of which 82.8% of HBsAg disappearance occurred at more than 48 weeks of treatment. In contrast, among 148 HBeAg-positive patients, those who achieved HBsAg disappearance/serological conversion (14/148) were treated for >48 weeks, suggesting that patients who responded well to pegylated interferon alpha-2a for HBV DNA and HBsAg need more prolonged treatment in order to maximize the chances of achieving immune control goals. a comparative study by Lamprteico P et al. pegylated interferon alpha-2a treatment for a decrease in HBsAg levels greater than 10% and less than 10% at 24 weeks of treatment in HBeAg-negative, genotype D patients with chronic hepatitis B treated for 48 and 96 weeks and with persistent viral rates at 1 year post-discontinuation. The results showed that for patients with >10% reduction in HBsAg levels at 24 weeks of treatment, the sustained viral response rate at 48 weeks of treatment was only 17%, significantly lower than that at 96 weeks of treatment, which was 58%, while for patients with <10% reduction in HBsAg levels at 24 weeks of treatment, the sustained viral response rates at 48 and 96 weeks of treatment were 9% and 12%, respectively, and the results also showed that patients with good response on treatment, for higher treatment, there is a greater need to extend treatment. In conclusion, because of the huge differences in the clearance of free virus, clearance of virus-infected hepatocytes, and half-life of hepatic HBV cccDNA in patients with chronic hepatitis B treated with interferon; patients' treatment, especially interferon-based antiviral therapy, has been judged by the achievement of durable immune control as a criterion for discontinuation, and patients with good response to treatment have to pursue higher immune In order to achieve higher immune control goals or even "clinical cure", more patients need to extend their treatment to achieve their goals, and individualized treatment can maximize their chances of achieving immune control.