1, chronic hepatitis B antiviral treatment when to change drugs? Nucleoside analogs are easy to produce drug resistance with long-term use, for which researchers have done a lot of research. Single use of a nucleoside analog, continuous use for more than 1 year, 10% of the role of drug resistance can occur. For this reason, some researchers have proposed that a nucleoside analogs used for three months HBV-DNA copy number does not change, or half a year when HBV-DNA has not yet turned negative, should be replaced with another nucleoside analogs. Other researchers have suggested that when a nucleoside analog has been used for 2 years, although drug resistance has not appeared, if the disease requires continued use of the drug, another nucleoside analog can be replaced. Or combined with another nucleoside analog. This can not only reduce the long-term use of drug resistance, but also save resources. 2, what kind of chronic hepatitis B for the first time to start a combination of drugs? At present, many researchers propose that for patients with chronic hepatitis B cirrhosis decompensation, patients who are eligible for application of nucleoside antiviral drugs (HBV-DNA positive). It is more reasonable to apply lamivudine + adefovir antiviral treatment at the beginning, not only to delay the time of drug resistance, but also to achieve the strong effect of combined antiviral, which is also the best match from the pharmacological point of view. 3, chronic hepatitis B application of nucleoside analogs drugs what time to stop? Since the application of nucleoside analogs clinical treatment of chronic hepatitis B for more than ten years, researchers have done a lot of discussion, agreed that HBV-DNA positive, after taking the drug since the date of conversion to negative and then take the drug for one year. Or HBeAg-positive people turn negative, then take medication for another six months. Despite the application of this drug withdrawal criteria, there are still relapses after drug withdrawal, how to do? I experience, for those who relapse, re-treatment, can still get better results. 4.How to reduce drug resistance and relapse of chronic hepatitis B treated with nucleoside analogs? I treat thousands of cases of chronic hepatitis B, I have the following experience: (1) Combination of drugs: Lamivudine combined with interferon. (i.e. ALT 80-200u, HBV DNA>106) lamivudine 0.1g once a day, interferon 300-500 units every other day) (2) sequential treatment, the first 3 months of lamivudine, the fourth month of combined interferon, the course of treatment for 6 months (ALT>200u and HBV DNA>107) (3) alternating combination therapy: the first 1 year of lamivudine. The treatment is effective, but the conditions for stopping the drug have not been reached, it can be combined with adefovir for 3 months, stop lamivudine, adefovir alone, and then use interferon for 6 to 12 months.