Currently there are five anti-HBV nucleotides and analogues that have been used clinically, and four of them have been used in China. 1, lamivudine lamivudine, LAM, domestic and foreign randomized controlled clinical trial results show that 100 mg of lamivudine taken orally once a day can significantly inhibit HBV DNA levels; HBeAg serological conversion rate increases with the extension of treatment time, 16%, 17%, 23%, 28% and 35% at 1, 2, 3, 4 and 5 years of treatment, respectively; ALT levels before treatment The rate of HBeAg serological conversion was higher in those with higher pre-treatment ALT levels. Randomized double-blind clinical trials have shown that lamivudine treatment for 3 years in patients with chronic hepatitis B with significant liver fibrosis and compensated cirrhosis can delay disease progression and reduce the incidence of hepatic decompensation and hepatocellular carcinoma. Patients with decompensated cirrhosis treated with lamivudine can also improve liver function and prolong survival. Overseas studies have shown that the efficacy of lamivudine in the treatment of chronic hepatitis B in children is similar to that in adults, with a good safety profile. The incidence of viral resistance mutations increases with prolonged treatment 14%, 38%, 49% and 66% in years 1, 2, 3 and 4, respectively. 2. adefovir dipivoxil, ADV, a randomized double-blind clinical trial in China and abroad, showed that oral adefovir in patients with HBeAg-positive chronic hepatitis B significantly inhibited HBV DNA restoration, promoted ALT normalization and improvement of liver tissue inflammation necrosis and fibrosis. In HBeAg-positive patients treated for 1, 2 and 3 years, the HBV DNA 1000 copies/mL was 28%, 45% and 56% respectively, and the HBeAg serological conversion rate was 12%, 29% and 43% respectively; the drug resistance rate was 0%, 1, 6% and 3, 1% respectively. In HBeAg-negative patients treated for 5 years, the rate of HBV DNA 1000 copies/mL was 67% and the rate of ALT normalization was 69%; at 4 and 5 years of treatment, the rate of hepatic inflammatory necrosis and fibrosis improvement was 83% and 73%, respectively; at 5 years of treatment, the incidence of cumulative drug resistance mutations was 29%, the incidence of virologic resistance was 20%, and the incidence of clinical drug resistance was 11 The incidence of mild creatinine elevation was 3%. Adefovir combined with lamivudine was effective in suppressing HBV DNA and promoting ALT normalization in lamivudine-resistant chronic hepatitis B. The incidence of drug resistance to adefovir was lower in the combined drug users. The results of several studies have shown that the combination of adefovir is effective in patients with lamivudine-resistant compensated and decompensated cirrhosis. 3, entecavir entecavir, ETV, a randomized double-blind controlled clinical trial showed that in HBeAg-positive chronic hepatitis B patients, 67% of HBV DNA decreased to less than 300 copies/mL, 68% of ALT normalized, and 72% of liver histology improved at 48 weeks of entecavir treatment, all better than those treated with lamivudine; but the two groups HBeAg seroconversion rates were similar 21% and 18%, [87]. In HBeAg-negative patients, the rate of HBV DNA reduction below the PCR level at 48 weeks of entecavir treatment was 90%, the rate of ALT recovery was 78%, and the rate of hepatic histological improvement was 70%. Long-term follow-up studies have shown that for those who achieve virologic response, continued treatment maintains a high level of HBVDNA suppression. A Japanese study showed a 3-year cumulative resistance rate of 1.7% to 3.3% for entecavir. The results also suggest that the use of entecavir 1,0 mg daily in patients who failed lamivudine treatment can also suppress HBV DNA and improve biochemical parameters, but the efficacy is lower than that of primary treatment, and the incidence of virological breakthrough is significantly higher, so it should not be advocated. The results of clinical trials in our country are basically similar to those reported above. 4, telbivudine, LdT, a 2-year global multicenter clinical trial showed that at 52 weeks of treatment in HBeAg-positive patients, HBV DNA in the telbivudine group decreased to below the level detected by PCR in 60,0%, ALT normalization rate in 77,2%, drug resistance rate in 5,0%, and liver histological response rate in 64,7%, all of which were However, the HBeAg seroconversion rate was 22.5%, similar to that of the latter; the HBV DNA suppression, ALT normalization rate and drug resistance rate of HBeAg-negative patients were also better than those of the lamivudine group at 52 weeks of treatment. At 2 years of treatment, the overall efficacy was better than that of the lamivudine group, except for the disappearance of HBeAg and seroconversion rate, and the incidence of drug resistance. A multicenter clinical trial in China also showed that its antiviral activity and incidence of drug resistance were better than those of lamivudine. Domestic and international clinical studies suggest that HBeAg-positive patients with baseline HBV DNA of 109 copies/mL and ALT?2ULN or HBeAg-negative patients with HBV DNA of 107 copies/mL have better efficacy and lower incidence of drug resistance at 1 and 2 years of treatment if they reach HBVDNA of 300 copies/mL at 24 weeks of treatment with telbivudine. The overall adverse event rate of telbivudine and lamivudine is similar, but the incidence of grade 3-4 creatine kinase CK, elevated at 52 and 104 weeks of treatment is 7, 5% and 12, 9% respectively, while the lamivudine group is 3, 1% and 4, 1% respectively. This drug has not yet been approved in China. In a randomized, double-blind controlled clinical trial, TDF or ADV treated HBeAg-positive patients with HBVDNA 400 copies/mL in 76% and 13%, respectively, and ALT reversion rate in 68% and 54%, respectively; in HBeAg-negative chronic hepatitis B at 48 weeks, HBVDNA 400 copies/mL in 93% and 63%, respectively; the study showed that the effect of HBV inhibition was better than that of ADV. The study showed that the effect of HBV inhibition was superior to that of ADV, and no resistance mutations associated with tenofovir were found. At 3 years of continuous treatment with tenofovir, 72% of HBeAg-positive patients and 87% of HBeAg-negative patients had a serum HBVDNA of 400 copies/mL, and no drug resistance mutations were found. 1. baseline testing of relevant indicators before treatment: 2. biochemical indicators, mainly ALT, AST, bilirubin, albumin, etc.; 2. virological markers, mainly HBV DNA and HBeAg, anti-HBe; 3. routine blood tests, serum creatinine and creatine kinase, etc., according to the needs of the disease. If conditions allow, it is best to perform liver aspiration before and after treatment. 2. Regular monitoring of relevant indicators during treatment: 1. biochemical indicators, once a month for 3 consecutive times after the start of treatment, and once every 3 months afterwards as the disease improves; 2. virological markers, mainly including HBV DNA and HBeAg, anti-HBe, generally tested once 1-3 months after the start of treatment, and once every 3-6 months afterwards; 3. regular testing according to the needs of the disease The blood count, serum creatinine and creatine kinase will be tested regularly according to the needs of the disease. 3. Prediction of efficacy and optimization of treatment: It has been shown that, in addition to baseline factors, the virological response in the early stage of treatment can predict the long-term efficacy and incidence of drug resistance. Accordingly, the concept of roadmap for nucleotides and analogues in the treatment of chronic hepatitis B has been proposed overseas, emphasizing the importance of early virological response to treatment and advocating the optimization of treatment based on HBV DNA monitoring results. However, the optimal time point for monitoring and the threshold for judgement may vary among drugs. Moreover, prospective clinical studies are needed to verify which treatment strategies and methods are more effective for those with inadequate response. 4. Pay close attention to the patient’s adherence to treatment: including the dose of medication, the method of use, and whether there is any omission of medication or self-discontinuation, to ensure that the patient has understood the possible risks of random discontinuation and to improve patient adherence. Prevention and management of rare and uncommon adverse reactions: Nucleotides and analogues are generally safe and well tolerated, but rare and uncommon serious adverse reactions do occur in clinical applications, such as renal insufficiency, myositis, rhabdomyolysis, lactic acidosis, etc., which should be a cause for concern. It is recommended to carefully consult the relevant medical history before treatment to reduce the risk. Patients with significantly elevated blood creatinine, CK or lactate dehydrogenase and corresponding clinical manifestations such as deterioration of general condition, obvious myalgia and muscle weakness should be closely monitored and once diagnosed with uremic syndrome, myositis, rhabdomyolysis or lactic acidosis, the drug should be discontinued or switched to other drugs in a timely manner and active therapeutic intervention should be provided.