Nucleoside analogs are currently one of the most important drugs used against the hepatitis B virus. The advantages of nucleoside analogs are that they are easy to apply, take one tablet orally every day, have few adverse effects, have few contraindications, and have strong viral inhibitory activity, which can improve the disease more quickly and are easily accepted by patients. However, nucleosides also have outstanding disadvantages, which are high relapse rate after discontinuation of the drug and the need for long-term medication, which may occur in the long-term drug resistance, thus affecting the efficacy. Over the years, with the popularization of antiviral treatment for chronic hepatitis B in China, more and more patients have been treated with nucleoside analogs, and they are facing the problem of “good on, bad off” in the use of these drugs. How can nucleoside analogs be easily and safely taken off, and achieve the so-called safe discontinuation? Achieving clinical cure is undoubtedly the best way. Authoritative guidelines have clearly pointed out that the ideal endpoint for the treatment of slow hepatitis B is to achieve HBsAg clearance and produce Anti-HBs antibodies, i.e. clinical cure. Numerous studies have confirmed that patients who achieve this endpoint have a low risk of cirrhosis and hepatocellular carcinoma, and their disease is in long-term remission. Second, durable HBeAg serologic conversion can also help to achieve longer-term disease remission, achieve safe drug discontinuation, and even induce HBsAg clearance. However, HBeAg serological conversion rates and HBsAg clearance rates obtained with nucleoside analog therapy are both low, with HBeAg serological conversion rates of various nucleoside (acid) analogs for 2-5 years of treatment not exceeding 30%, and HBsAg clearance rates even closer to natural clearance rates. Clearly, for patients treated with nucleoside analogs, achieving safe discontinuation requires finding other drugs to help. In fact, interferon therapy is more advantageous in achieving clinical cure and HBeAg serologic conversion. Compared to the single antiviral effect of nucleosides, pegylated interferon not only has an antiviral effect, but also helps the host achieve immune control of the hepatitis B virus through immunomodulation, resulting in durable HBeAg seroconversion and even HBsAg clearance. It is based on this advantage that pegylated interferon has been able to achieve true successful treatment of slow hepatitis B – clinical cure – with its limited course of therapy, eventually making it possible for some populations to reach safe discontinuation of the drug. Studies have already shown for example the results of the OSST study that patients treated with nucleoside analogues treated with pegylated interferon alpha-2a have a nearly 2-fold increased chance of achieving HBeAg serologic conversion within 1 year compared to continued nucleoside analogues. In particular, for patients with cleared HBeAg and low HBsAg levels, the chance of achieving HBsAg clearance can reach 25%. In conclusion, for patients who expect to have a higher quality of life and pursue a limited course of treatment to achieve “major triplet” to “minor triplet” or clinical cure, the problem of “good up but bad down” arising from nucleoside drug therapy is a good one. “For patients who are already treated with nucleoside analogs, if their disease is stable and they wish to stop taking them, they still have the opportunity to shorten the treatment course with pegylated interferon and strive for clinical cure.