Entecavir (ETV) is now one of the drugs of choice for the treatment of chronic active hepatitis B. Many patients have learned about this drug from a variety of channels, and outpatient clinics often encounter some patients who come to consult the therapeutic efficacy and safety of the drug, the following I will give a brief description of some basic information about this drug and some of the problems that patients are concerned about for your reference: Yuan Gang, Department of Hepatology, Ningbo Second Hospital 1. What is the mechanism of ETV in the treatment of chronic active hepatitis B? A: As we all know, chronic active hepatitis B is caused by the presence of a large number of replicable hepatitis B viruses in the body of chronic hepatitis B patients. The natural history of chronic hepatitis B includes three phases: immune-tolerant, immune-activated, and inactive phases. Simply put, the immune tolerance period is a common category of young patients in outpatient clinics, who often have a high number of hepatitis B viruses, but their liver function has always been normal, this type of patients are in a relatively balanced state due to the immune tolerance of the body does not automatically clear the virus that already exists in the body, so at this time should not be antiviral treatment (unless liver ultrasound or liver puncture suggests that the liver has inflammation of more than G2, or severe hepatic (unless liver ultrasound or liver puncture indicates that the liver has inflammation above G2 or severe liver fibrosis or even cirrhosis). In my clinical practice, I have encountered some patients who used nucleoside analogs (including ETV) in this phase for some reasons, but the therapeutic effect is not satisfactory, but because of the self-stopping of the drug caused by the rebound of the virus, resulting in the onset of severe hepatitis, which is just like stirring up a hornet’s nest, which is more than worth the loss. Immune activation period refers to the body’s own clearance of hepatitis B virus due to a variety of factors (mostly occurring in 20-45 years old patients), patients can simply be understood as the body has produced a certain anti-hepatitis B virus ability, began to take the initiative to clear the presence of hepatitis B virus in the body, but because of this active clearing of the hepatitis B virus is imperfect, relying on the patient’s own immunity can not completely clear the body of the hepatitis B virus. The patient’s own immunity alone cannot completely remove the hepatitis B virus from the body! This is the best time for us to control the hepatitis B virus, that is to say, we can use ETV, a powerful antiviral drug, which can “pretend” to be the raw materials needed for the replication of the hepatitis B virus and embedded in the replication chain of the hepatitis B virus, so that the raw materials behind it can not continue to join, which will lead to the termination of the replication of the hepatitis B virus. In the end, the number of hepatitis B virus in the patient’s body drops sharply, so that the body’s immunity has a chance to completely suppress the hepatitis B virus and achieve the goal of clinical cure (most of them take about 5 years). Maybe patients will ask, what about the inactive phase? Inactive stage is actually equivalent to clinical cure, which is manifested by negative HBeAg, positive anti-HBe, undetectable HBV DNA (PCR method) or below the lower limit of detection, normal ALT / AST level, and no obvious inflammation in liver histology. That is to say, they have become real “small triple positive” (some patients with “small triple positive” have high hepatitis B virus count, which is actually due to the mutation of hepatitis B virus, and it is false “small triple positive”)! As mentioned above, the inactive phase is the third phase of the natural history of chronic hepatitis B. Unfortunately, not most patients with chronic hepatitis B can reach the third phase, which often requires the help of anti-hepatitis B virus medications. Most patients repeat the first and second phases over and over again, which causes repeated liver inflammation, and ultimately leads to liver fibrosis and cirrhosis, and in severe cases, liver failure and primary hepatocellular carcinoma. 2. How safe is ETV in treating chronic hepatitis B? A: ETV is the first-line drug available for CHB treatment at present, with good safety in clinical application. The drug was listed in 2005, in the cautious factor, I have been in the early stage did not dare to use the drug, because of animal experiments the drug when the dose to 40 times the human dose, the incidence of lung tumors in male or female mice increased. Lung cell hyperplasia first appeared in mice, followed by lung tumors, but no lung cell hyperplasia was found in rats, dogs and monkeys given the drug, suggesting that lung tumors occurring in mice may be species-specific, i.e., occurring only in mice. and the dose relative to human body weight is about 48,000 times higher. With the extensive use of this drug in the international arena, there has not been a single case of ETV causing serious side effects such as tumorigenesis in the world in the past 8 years, so it is safe for clinical use.3. Is ETV the ideal drug for the initial treatment of CHB? A: ETV is one of the ideal drugs for the initial treatment of CHB, especially for high viral load and progressive liver disease.3. Can ETV be used for chronic hepatitis B that fails to be treated with adefovir and lamivudine? A: ETV is one of the core drugs for the current treatment of refractory chronic hepatitis B. The combination of ETV and ADV is one of the options for refractory CHB.4. Can ETV prevent primary liver cancer and reduce the mortality rate of serious liver diseases? A: According to the evidence of evidence-based medicine nowadays, the effects of preventing primary liver cancer and reducing the mortality of serious liver diseases need to be further observed.5. Is it suitable to discontinue ETV as it is effective in suppressing HBV DNA? What is the impact of a limited regimen on outcomes? A: Nowadays, the European guidelines for the prevention and treatment of chronic hepatitis B are very thorough, requiring hepatitis B surface antigen to be negative in order to stop the drug, not only the disappearance of serum hepatitis B HBVDNA, so the disappearance of serum hepatitis B HBVDNA is not an indicator of stopping the drug, but the regular detection of hepatitis B E antigen and hepatitis B virus surface antigen. Personal experience, if it is “triple positive” chronic hepatitis B patients, if the E antigen turns negative, E antibody turns positive, and the surface antigen titer is less than 100, you can consider stopping the drug, if it is “false triple positive” chronic hepatitis B patients, the surface antigen titer is less than 10, you can consider stopping the drug, this is only for the purpose of the drug. In the case of “pseudo-small triple” chronic hepatitis B patients, the surface antigen titer is less than 10, and the drug can be considered to be discontinued. The effect of limited course of treatment on the outcome is not yet fully understood, I personally recommend at least oral ETV for more than 5 years, and ultimately consider whether to stop the drug with reference to whether the E antigen has turned negative, whether the E antibody has turned positive (only for triple triple positive, because the “pseudo-small triple positive” itself has already been so), and surface antigen titer, because now various large-scale clinical studies suggest that a long course of treatment is beneficial to the patients, and it is also necessary to consider whether to stop the drug. Research suggests that a long course of treatment is favorable to the long-term prognosis of patients. 6. Is ETV effective for all patients with hepatitis B? A: ETV is not a universal antiviral drug, and treatment still needs to be individualized (condition, population). If patients who have previously taken lamivudine resistance are not suitable to use entecavir, the long-term application of ETV is a costly expense, the current national conditions determine that it is not possible for all patients to take the drug, the optimization of nucleoside analog combination therapy advocated by the domestic experts is still of some value.7. What should be done if ETV resistance occurs? A: The law of the biosphere suggests that where there is oppression, there will be resistance, and the prolonged use of any antibiotic will eventually lead to drug resistance of pathogens, which is the law of natural selection and cannot be questioned! So entecavir is also resistant, but now it is the drug with the lowest resistance rate among the nucleoside analogs, with a 4-year resistance rate of only 0.4%. If resistance occurs, long-term antiviral therapy and combination antiviral therapy are required. It is best to choose ETV antiviral therapy initially to minimize the rate of resistance, which will be greatly increased if other nucleoside analogues that are prone to resistance (e.g., lamivudine, telbivudine) are used first and then ETV is used after resistance has occurred! At this time, it is not recommended to use ETV, and it is recommended to add adefovir on top of the original treatment.8. What should I do if I have been on treatment for more than 5 years and can’t meet the criteria for stopping the drug as you said? A: No treatment regimen is perfect, and it is true that a small number of patients do not reach the treatment goal, such as always being “triple positive”, or surface antigen titer is always high, now the proposed solution is to combine or sequential long-acting interferon therapy, but the efficacy and safety of combining ETV with IFN/PEG IFN need to be evaluated. needs to be further evaluated for efficacy and safety, but it is promising to be one of the options available in the future. In the end, as a doctor, chronic hepatitis B can not be completely cured on a large scale, so I hope that the majority of patients should establish confidence in overcoming the disease, and I believe that with the progress of medical science, chronic hepatitis B will eventually become the dust of history! Do you believe it? Anyway, I believe it ……