Great progress has been made in the treatment of chronic hepatitis B since the 1990s, when antiviral therapy for chronic hepatitis B was introduced. A fundamental breakthrough has now been made in terms of the effectiveness and feasibility of treatment. There are four nucleoside (acid) analogues approved for antiviral treatment of chronic hepatitis B in China – lamivudine, adefovir, entecavir and telbivudine. Most of these drugs can act as single agents or (and) in combination to achieve the basic clinical therapeutic goal of sustained inhibition of HBV-DNA replication. With the implementation of long-term treatment strategies, the risk of nucleoside (acid) analogue resistance development increases, while the forms of HBV resistance variants will increase with the increase of drug classes and their applications. In fact, the frequent emergence of drug resistance in clinical anti-HBV therapy has become a serious and important “clinical problem” that we must face, and the new concept of moving forward the time point of drug resistance management in the process of clinical drug resistance management has gradually become a consensus among virologists and clinicians. I. The necessity and reality of HBV drug resistance management Ten years of clinical practice of nucleoside (acid) analogue anti-HBV therapy has proven its “effectiveness”, “ease of use”, “safety “However, the emergence of drug resistance during treatment has become one of the biggest “clinical problems” affecting long-term antiviral therapy. Once drug resistance occurs, it may be accompanied by loss of antiviral drug efficacy, increase in clinical HBV load and increase in ALT, thus affecting and changing the clinical outcome of patients. This can be manifested as hepatitis recurrence, acute exacerbation of liver disease, cirrhosis, and even liver failure and death; for liver transplant patients, drug resistance will lead to rejection of liver grafts and liver transplant failure. In addition, drug resistance may pose a great danger to public health, as nucleoside analogue resistance mutations may theoretically lead to mutations in the HBsAg “a” determinant cluster, rendering the current hepatitis B vaccine unprotective; there is also the possibility of transmission of lamivudine-resistant hepatitis B virus strains, thus altering the natural history of chronic hepatitis B. There is also the possibility of transmission of lamivudine-resistant hepatitis B virus strains, thus altering the natural history of chronic hepatitis B and making the prevention and treatment of chronic hepatitis B difficult. The specific reality of clinical resistance management is that the current main “rescue” therapy for drug resistance may reduce the efficacy of subsequent therapeutic agents, increase the risk of resistance, or even develop so-called “multidrug-resistant hepatitis”, limiting the choice of further therapeutic agents. The choice of further therapeutic agents is limited. Therefore, effective management of clinical resistance to anti-HBV therapy with nucleoside (acid) analogues, enhanced monitoring and effective intervention are necessary to avoid or delay the occurrence of drug resistance in clinical practice. Second, drug resistance and drug resistance mutation Drug resistance is due to adaptive mutation of HBV to the drug, resulting in a decrease in the sensitivity of the drug to inhibit the viral effect, and the corresponding clinical manifestation is the re-replication of the inhibited virus (HBV re-elevation) and the reappearance of liver damage manifestations (ALT re-elevation). Clinical findings show that drug resistance depends on the patient’s response to antiviral drug therapy, and the current virological response to antiviral drug therapy is mainly divided into: complete response, referring to HBV-DNA.