I. Nucleoside (acid) analog therapy. (A), has been applied to the clinical anti-HBV nucleoside (acid) analogs of five kinds of drugs, China has listed four kinds. 1, lamivudine (lamivudine, LAM): randomized controlled clinical trials at home and abroad showed that 100 mg of lamivudine orally once a day can significantly inhibit the level of HBV DNA; HBeAg serological conversion rate with the prolongation of the treatment time to improve the treatment of 1, 2, 3, 4, and 5 years, respectively, for 16%, 17%, 23%, 28%, and 35%; before treatment Those with higher ALT levels had higher HBeAg serologic conversion rates. Randomized double-blind clinical trials have shown that 3 years of lamivudine treatment in patients with chronic hepatitis B with significant hepatic fibrosis and compensated cirrhosis can delay disease progression and reduce the incidence of hepatic decompensation and hepatocellular carcinoma. Patients with decompensated cirrhosis can also improve liver function and prolong survival after lamivudine treatment. The results of foreign studies show that the efficacy of lamivudine in the treatment of chronic hepatitis B in children is similar to that of adults, and the safety is good. Clinical studies in China also show similar clinical efficacy and safety. Taihe County Hospital of Traditional Chinese Medicine, Department of Hepatology, Wyatt over lamivudine adverse reaction incidence is low, the safety is similar to placebo. With the prolongation of the treatment time, the incidence of viral drug resistance mutations increased (14%, 38%, 49% and 66% in the first, second, third and fourth years, respectively). 2, adefovir dipivoxil (adefovir dipivoxil, ADV): randomized double-blind clinical trials at home and abroad showed that HBeAg-positive patients with chronic hepatitis B oral adefovir can significantly inhibit the replication of HBV DNA, promote ALT revert to normal, and improve the inflammation and necrosis of the liver tissue and fibrosis. In HBeAg-positive patients treated for 1, 2, and 3 years, HBV DNA <1000 copies/mL was 28%, 45%, and 56%, respectively; HBeAg serologic conversion rate was 12%, 29%, and 43%, respectively; and resistance rate was 0%, 1.6%, and 3.1%, respectively. In HBeAg-negative patients treated for 5 years, 67% had HBV DNA <1000 copies/mL, and 69% had ALT reversion rate; 83% and 73% had improvement in the degree of hepatic inflammation, necrosis, and fibrosis, respectively, at 4 and 5 years of treatment; 29% cumulative drug-resistant mutations, 20% virologic resistance, and 11% clinical resistance at 5 years of treatment; and 11% mild myasthenia gravis. 11%; mild creatinine elevation was seen in 3%. Adefovir in combination with lamivudine is effective in inhibiting HBV DNA and promoting ALT recovery in lamivudine-resistant chronic hepatitis B, and the incidence of resistance to adefovir is lower in those who take the combination. The results of several studies show 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, for HBeAg-positive chronic hepatitis B patients, entecavir treatment for 48 weeks, HBV DNA decreased to less than 300 copies / mL of 67%, ALT recovery of 68%, there is a histological improvement in the liver of 72%, are superior to those who receive lamivudine treatment; but both groups HBeAg seroconversion rates were similar in both groups (21% and 18%). In HBeAg-negative patients, 90% of HBV DNAs fell below PCR detection level, 78% of ALTs reverted, and 70% of liver histology improved at 48 weeks of entecavir treatment. Long-term follow-up studies have shown that continued treatment maintains high HBVDNA suppression in those who achieve a virologic response. A Japanese study showed a 3-year cumulative resistance rate to entecavir of 1.7% to 3.3%. The results of the study also suggest that the use of entecavir 1.0mg per day in patients who failed lamivudine therapy can also inhibit HBV DNA and improve biochemical indicators, but the efficacy is lower than that of the primary treatment, and the incidence of virological breakthrough increased significantly, so it is not appropriate to advocate. The results of clinical trials in China are basically similar to the above reports. 4, tibivudine (telbivudine, LdT): a 2-year global multicenter clinical trial showed that HBeAg-positive patients treated for 52 weeks, tibivudine group HBV DNA decreased to the PCR method below the level of 60.0%, ALT revert rate of 77.2%, the incidence of drug resistance 5.0%, liver histology response rate of 64.7%, are better than lamivudine treatment. The HBeAg seroconversion rate (22.5%) was similar to that of the lamivudine group, while the HBV DNA suppression, ALT recovery rate and drug resistance rate of the HBeAg-negative patients were better than those of the lamivudine group at 52 weeks of treatment. At 2 years of treatment, its overall efficacy (except for the disappearance of HBeAg and seroconversion rate) and the incidence of drug resistance were also better than that of lamivudine group. Multicenter clinical trials in China have also shown that its antiviral activity and the incidence of drug resistance are better than that of lamivudine. Clinical studies at home and abroad suggest that HBeAg-positive patients with baseline HBV DNA <109 copies/mL and ALT?2ULN, or HBeAg-negative patients with HBV DNA <107 copies/mL, who have achieved HBVDNA 300 copies/mL after 24 weeks of treatment with telbivudine, will have a better therapeutic efficacy and lower incidence of drug resistance when treated for 1 or 2 years. The overall incidence of adverse events for telbivudine was similar to that of lamivudine, but grade 3-4 creatine kinase (CK) elevations at 52 and 104 weeks of treatment were 7.5% and 12.9%, respectively, compared with 3.1% and 4.1% in the lamivudine group. 5, tenofovir disoproxil fumarate (TDF): TDF and adefovir ester structure is similar, but less nephrotoxic, the therapeutic dose of 300 mg per day. this drug has not yet been approved for marketing in China. In a randomized double-blind controlled clinical trial, 76% and 13% of HBeAg-positive patients with HBVDNA<400 copies/mL were treated with TDF or ADV, and 68% and 54% of HBeAg-negative patients were treated with ALT; 93% and 63% of HBeAg-negative patients were treated with HBVDNA<400 copies/mL at 48 weeks, and the inhibition of HBV was superior to that of ADV in the study. HBV than ADV, and no tenofovir-associated resistance mutations were detected. When tenofovir was continuously applied for 3 years, 72% of HBeAg-positive patients and 87% of HBeAg-negative patients had serum HBVDNA <400 copies/mL, and no drug-resistant mutation was found. (ii) Issues related to nucleoside (acid) analog therapy. 1, before the treatment of relevant indicators of baseline testing: (1), biochemical indicators, mainly ALT, AST, bilirubin, albumin, etc.; (2), virological markers, mainly HBV DNA and HBeAg, anti-HBe; (3), according to the needs of the condition of the test blood routine, serum creatinine and creatine kinase and so on. If conditions permit, it is best to perform liver puncture before and after treatment. 2.Regular monitoring of relevant indicators in the course of treatment: (1), biochemical indicators, once a month after the start of treatment, three times in a row, and then once every three months with the improvement of the condition; (2), virological markers, including HBV DNA and HBeAg, anti-HBe, generally 1-3 months after the start of treatment, and then every 3-6 months; (3), according to the needs of the condition, regular blood tests, serum creatinine and creatinine kinase. Regular testing of blood routine, serum creatinine and creatine kinase and other indicators. 3. Predicting efficacy and optimizing treatment: Some studies have shown that, in addition to baseline factors, the early virological response to treatment can predict its long-term efficacy and the incidence of drug resistance. Accordingly, foreign countries have put forward the roadmap concept of nucleoside (acid) analogues for the treatment of chronic hepatitis B, emphasizing the importance of the early virological response to treatment and advocating the optimization of treatment according to the results of HBV DNA monitoring. However, the optimal monitoring time points and judgmental thresholds may vary from drug to drug. Furthermore, 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 patients' adherence to treatment: including dosage, method of use, and whether there is any omission or discontinuation of drugs, etc., to ensure that patients are aware of the possible risks of stopping medication at will, and to improve patients' adherence to treatment. 5. Prevention and treatment of rare and uncommon adverse reactions: the overall safety and tolerability of nucleoside (acid) analogs are good, but there are rare and uncommon serious adverse reactions, such as renal insufficiency, myositis, rhabdomyolysis, lactic acidosis, etc., which should be paid attention to in clinical application. It is recommended that a careful history be taken before treatment to minimize the risk. Patients with significant increase in blood creatinine, CK or lactate dehydrogenase during treatment and corresponding clinical manifestations such as deterioration of general condition, obvious myalgia, muscle weakness, etc. should be closely observed, and once the diagnosis of uremia, myositis, rhabdomyolysis, or lactic acidosis is confirmed, the drug should be stopped or switched to other drugs in a timely manner, and active corresponding therapeutic interventions should be given.