Since 16 years of using nucleoside analogs, the biggest problem is drug resistance, and some patients really suffer. From the launch of domestic entecavir and the rapid affluence of the people, in recent years my clinic generally only use entecavir and tenofovir, which are two first-line nucleoside analogues that are rarely resistant. Entecavir efficacy is significantly higher than second-line drugs, but about 10% of the effect is poor, the virus 3, 4 times coies/ml after hovering not to fall. As long as alcohol is prohibited, the initial treatment is rarely resistant, but those who are resistant to lamivudine or telbivudine will be cross-resistant. In the 3 years since the use of domestic entecavir, my clinic has probably nearly 2,000 patients, there are absolutely no adverse reactions, and there are no patients who have stopped taking the drug as a result. In addition, the impact on fertility, fetal teratogenesis can not be excluded. Tenofovir is more effective than entecavir. It has been used for 11 years as the main drug for AIDS and 8 years for hepatitis B. So far, no definite resistance has been reported at home or abroad. Alcoholism, chemotherapy or adrenocorticosteroids significantly affect its efficacy, and no resistance has been seen. Our self-pay pharmacy has been supplying this drug for more than 3 years and more than a thousand people have applied it in my outpatient clinic, mostly pregnant women with hepatitis, followed by cirrhosis, and again by patients with various drug resistance. The clinical impression is that it has a slightly shorter turnaround time for viral and E antigen, a possibly slightly faster reduction in surface antigen titers, a high reversal rate for liver fibrosis and mild cirrhosis reported abroad, and a possible substantial reduction in the incidence of hepatocellular carcinoma. In addition, this drug does not affect fertility or breastfeeding. However, tenofovir has slightly more adverse effects than entecavir, such as chronically high transaminases, rash, frequent stools and some other discomfort, and a few people have discontinued the drug because it was intolerable. Many people worry about tenofovir nephrotoxicity, in fact, that is in AIDS patients; in chronic hepatitis B actual only a very small number of people have a slight renal tubular damage, manifested as 24-hour urine β2 microglobulin increased, 3 to 6 months after the change of drugs can be normalized. The problem is that some patients with hepatitis B who may have potential renal dysfunction, such as over 50 years old mostly have some renal arteriosclerosis, high blood pressure, high creatinine or a small amount of protein in the urine routine, if they have been lamivudine resistant in the past, they can only use tenofovir in the long run. Also, “small three” patients with mild cirrhosis, if the next of kin have malignant tumors, especially liver cancer, in order to minimize the occurrence of liver cancer, it is also best to use tenofovir. But how can these patients safely take tenofovir? 1, long-term taking adefovir can not directly switch to tenofovir to avoid inheriting the nephrotoxicity of adefovir, must first use entecavir (once lamivudine resistant people must be 2 tablets per day) for 3 months, check the 24-hour urine β2 microglobulin quantification normal before changing tenofovir. 2, these patients may have reduced glomerular filtration rate, if the conventional dose of 1 tablet per day, blood concentration is too high will occur nephrotoxicity. Real-time serum creatinine quantification and calculation of serum creatinine clearance can be equivalent to glomerular filtration rate and reduce the daily dose of medication. (1) Calculation formula: (140-age) x weight kg / 0.818 x serum creatinine Serum creatinine clearance ≥ 90%: 1 tablet per day. (2) 60-90%: 1 tablet 36 hours, 8 am on the first day, 8 pm on the second day, no dose on the third day, and so on. (3) ≤ 60% ≥ 30%: half a tablet per day. To ensure accurate serum creatinine quantification, reduce meat and physical activity 2 days before the examination. 3.Check the 24-hour urine β2 microglobulin quantification regularly, usually every 3 months, or once a month if necessary. If the quantification increases, you should switch to entecavir for 3-6 months, then recheck the 24-hour urine β2 microglobulin quantification and switch back to tenofovir after normalization.