How do nucleoside analogs achieve safe discontinuation?

In clinical practice, more and more patients are receiving nucleoside analogue antiviral therapy, and nucleoside analogue antiviral therapy has indeed brought great benefits to the majority of patients, with long-term suppression of the virus, stable liver function and improved liver histopathology. Many patients wish to discontinue the drug after long-term use, partly because they are concerned about the safety of long-term use and partly because they fear that long-term use may increase the risk of drug resistance. A survey showed that 90% of patients desire to be able to safely discontinue their medication. The ideal endpoint of chronic hepatitis B treatment is the disappearance of hepatitis B surface antigen, but this goal is difficult to achieve with long-term nucleoside analog therapy. A study called “NEW SWITCH” was conducted at Chongqing Medical University to evaluate the possibility of HBsAg conversion in HBeAg-positive chronic hepatitis B patients treated with nucleoside analogue C through long-acting interferon conversion therapy. The NEW SWITCH study is a multicenter, randomized, unblinded study. HBeAg-positive chronic hepatitis B patients who achieved partial response (response defined as HBVDNA <200 IU/ml and HBeAg conversion) after 1-3 years of nucleoside analogue therapy were included in the study. All subjects were randomly assigned 1:1 to receive long-acting interferon therapy for 48 weeks or 96 weeks (the first 12 weeks in combination with NUC therapy), with follow-up monitoring for 48 weeks after cessation of long-acting interferon therapy. The rate of HBsAg conversion at 48 weeks of treatment was the primary endpoint of this interim analysis. A total of 303 patients were randomized and included in the ITT population. The mean age was 34.2 years. The baseline qHBsAg and HBeAg levels were 3.105 (±0.7844) logIU/ml and -0.654 (±0.1515) logPEIU/ml, respectively. After 48 weeks of treatment, the HBsAg conversion rate and seroconversion rate reached 16.2% and 12.5%. Patients achieving HBsAg ≤1000 IU/ml, ≤100 IU/ml, and ≤10IU/ml were 65.7%, 46.5%, and 25.7%, respectively. A total of 58.7% of patients achieved HBeAg serological conversion. Across the study, 91.7% of subjects maintained HBV DNA suppression and 59.1% achieved ALT reversion (defined as ALT ≤ ULN). Patients with low qHBsAg levels (<1500 IU/ml) at baseline achieved higher rates of HBsAg conversion and higher rates of HBsAg <10 IU/ml at the end of the analysis (31.2% and 47.8%, respectively). In this study, it was found that patients who had undergone long-term nucleoside analogue antiviral therapy could be converted to long-acting interferon antiviral therapy to achieve hepatitis B surface antigen conversion, especially for patients with hepatitis B surface antigen quantification below 1500 IU/ml, and this "relay" antiviral therapy could be applied to remove This is especially true for patients with hepatitis B surface antigen quantification below 1500 IU/ml.