Lamivudine Lamivudine is the first nucleoside (acid) analogue approved for HBV, which is a levorotatory dideoxycyclic cytidine. Lamivudine has a rapid onset of action, with HBV DNA concentrations decreasing or even turning negative in 1 to 3 weeks, but it does not remove cccDNA from hepatocytes, so long-term use is required to achieve lasting effects. Lamivudine has accumulated rich experience in the treatment of chronic hepatitis B and HBV-related liver diseases, with clear effects in controlling disease progression and improving prognosis, but the incidence of drug resistance variation due to long-term treatment is high, which is not effective for some patients. Lamivudine is safe and effective in pediatric patients and can stabilize or improve liver function in patients with decompensated cirrhosis, thereby precluding or delaying the need for liver transplantation. The main advantages of lamivudine are ease of use and better tolerability, but a low durable response rate and a significantly higher risk of long-term treatment-resistant mutations. Adefovir It is an acyclic analogue of deoxyadenosine 5′-monophosphate, which inhibits HBV DNA reverse transcription and the viral replication process. The main advantage of adefovir is its antiviral activity against lamivudine resistance variant and low resistance variant rate, but its antiviral effect is weaker than lamivudine and slower onset of action. It is recommended to add rather than switch to adefovir treatment for lamivudine-resistant patients. The combination of lamivudine and adefovir can be chosen for primary treatment of patients with decompensated cirrhosis to reduce the risk of drug resistance and to enable rapid suppression of viral replication. Adefovir has potential nephrotoxicity, and monitoring of serum creatinine levels every 3 months is necessary for patients at risk of renal insufficiency and for patients treated with adefovir for more than 1 year. Entecavir Selective inhibition of HBV DNA polymerase, with effects on the initiation of viral DNA replication, reverse transcription of the negative and positive strands, and lengthening of the positive strand. Entecavir (0.5 mg/d) is superior to lamivudine for viral inhibition. Entecavir is not toxic to mitochondria and is the most potent and relatively safe antiviral agent available. Entecavir has a strong and long-lasting effect, and the incidence of long-term drug resistance is extremely low. However, the cost is relatively high compared to lamivudine and adefovir, and the incidence of adverse events during entecavir treatment is similar to that of lamivudine. No differences in the incidence of primary hepatocellular carcinoma or other tumors have been found to date in patients treated with entecavir or lamivudine. Tebivudine Levonucleosides are levorotide isomers of natural nucleosides and all levonucleosides have potent and specific inhibition of hepatophilic viruses. The inhibition of HBV replication by tebivudine is stronger than that by lamivudine. Investigators concluded that tebivudine was more effective than lamivudine at 1 year in treating both HBeAg-positive and HBeAg-negative chronic hepatitis B, with a smaller proportion of treatment failures and fewer occurrences of drug resistance. The tolerability of telbivudine is good and its safety profile is comparable to that of lamivudine. Although the rate of resistance to telbivudine is lower than that of lamivudine resistance, it increases exponentially after 1 year of continuous treatment. The drug has a higher rate of HBeAg/anti-HBe serologic conversion in HBeAg-positive patients treated with this drug than the first three drugs. The drug has been on the market for a short period of time, and its antiviral effects, resistance rate, long-term efficacy and safety need to be further confirmed. The treatments used today for chronic hepatitis B do not eradicate HBV, and the long-term efficacy does not yet reach the desired endpoint of cure. Therefore, the patient’s age, severity of liver disease, likelihood of response, and potential adverse effects should be taken into account before treatment is administered. Patients with hepatitis B for whom antiviral therapy is not yet indicated need to be tested and followed up, and those who are eligible for antiviral therapy should be treated as early as possible. Issues to consider when deciding which antiviral agent to choose as first-line therapy include the safety and efficacy of the regimen, the risk of viral resistance, the cost of treatment, and patient preference, and for women of childbearing age, when and if they intend to become pregnant. For patients in the first treatment in the surrogate phase, it has not been shown which is superior, interferon or nucleoside (acid) analogs, both of which are currently recommended. In the future, emphasis should be placed on the development of drugs with different mechanisms of action and targets, as well as on the study of treatment regimens combining different drugs with the aim of improving the outcome of chronic hepatitis B treatment.