1, the first treatment of patients and the treatment of patients or different? In fact, the so-called transthyretic treatment is after the treatment of nucleoside analogues, of course, a part of patients after interferon treatment is also called transthyretic. The first time patients, that is, patients who have never received antiviral treatment. As the antiviral treatment proceeds, the number of patients undergoing treatment is likely to increase gradually. Yuan Jing, Department of Hepatology, Shenzhen Third People’s Hospital 2. What is the proportion of first-time patients? There are more primary patients in general, but the number of treated patients will gradually increase. The reason for the increase is that, firstly, the doctor may not be very clear when choosing the medication; secondly, the patient does not take the medication timely and on time; thirdly, the medication itself has some limitations. For example, the antiviral ability of some drugs is not very strong, and the resistance barrier is not very high, so it is easy to treat viral rebound, or poor response, so that the treated patients will theoretically increase gradually. 3.What are the clinical situations considered to be treated? One is to take lamivudine in the process of viral rebound, or adefovir viral rebound; did not meet certain criteria to stop the drug, and then relapse belongs to the treatment; the third is to meet the criteria to stop the drug, after stopping the drug rebound also belongs to the treatment. 4.What is the treatment plan for patients undergoing treatment? In principle, the treatment plan is based on the current drug use and the previous drug use. Most of our patients with treatment are related to lamivudine and adefovir. For example, if you are taking lamivudine, and drug resistance occurs during the treatment process or if you have relapsed after reaching the discontinuation criteria with lamivudine, once you treat these patients again, you should consider combining the drugs as much as possible, that is, choosing a drug that is not cross-resistant together. For example, lamivudine can be combined with adefovir, or tenofovir, or two brand new ones: telbivudine plus adefovir, to obtain better viral suppression and E antigen seroconversion rate. In the case of adefovir resistance, the options may be a bit more varied, with the option of adding lamivudine for adefovir resistance, or tenofovir, or entecavir alone, with tenofovir also available. Now the published guidelines for treated patients, especially adefovir and lamivudine two drugs, in principle, no longer advocate single use. 5, lamivudine and adefovir no cross-resistance? For example, for those who have used lamivudine, because there may be cross-resistance with telbivudine and entecavir, if these treated patients are treated again, it is currently advocated that any one drug can be selected in the same class, plus another class of drugs that do not have cross-resistance. It is not advisable to choose a single drug with cross-resistance, perhaps adefovir plus telbivudine or entecavir, especially telbivudine may have a higher rate of E antigen conversion in patients with major triplets. 6. If adefovir is resistant to the drug or the virus rebound after stopping the drug and relapses, do they combine with tipifudin and entecavir, and is there a combination of drugs for different patients? Yes, patients treated with adefovir can choose to add telbivudine or lamivudine or entecavir, but in fact, if they are hepatitis B E antigen positive, more often they choose to add telbivudine. The E antigen conversion rate is higher with adefovir plus telbivudine than with lamivudine or entecavir. Of course some special patients, with cirrhosis or other patients with renal impairment, are more likely to consider adding telbivudine. This is because many studies have proven that telbivudine has a protective effect on renal function and can improve renal function. 7.Nucleoside analogs in general are not effective in treatment, rebound or relapse, now the recommended combination of drugs, what is its therapeutic effect? Will it be more difficult to treat? The treatment difficulty is definitely increased than the original, which is undeniable, because after all, there is already a drug-resistant base. In fact, after the lamivudine resistance we know, it will play a role in inducing resistance to many other antiviral drugs, including adefovir and entecavir. If you switch to some more drugs, the chance of resistance is definitely greatly increased. Therefore, the combination treatment of treated patients, although the effect is still possible, but than the initial treatment of patients increased the difficulty, resulting in poor efficacy, the future occurrence of the possibility of drug resistance, the proportion of E antigen conversion, etc. will be different from the initial treatment. For patients, should first first treatment firm confidence treatment, can not just stop, may lead to drug resistance, will increase the difficulty of future treatment. 8, interferon treatment is not effective in patients how to treat? Because the final clearance of hepatitis B must rely on immunity, interferon can improve the role of immunity. But interferon, after all, has many side effects and limited efficacy, unlike nucleoside analogs that quickly turn DNA negative once eaten, interferon is unlikely to achieve such an effect soon. The patient is faced with many problems with interferon therapy. Firstly, side effects, and secondly, lack of efficacy or non-response to treatment may occur during the course of treatment. Poor efficacy means that the HBV DNA decreases to a certain extent, but not enough. In the case of non-response, the HBV DNA does not decrease or even increases slightly, which is called ineffective interferon therapy. Should we continue interferon therapy for such patients or switch to other drugs? In principle, we will observe such patients for about six months for short-acting interferon and a year for long-acting interferon. Of course, we have to analyze the patient’s specific situation. This type of drug is not effective, the patient has to suffer serious side effects, I would advocate timely replacement of drugs. 9. What is the standard for short-acting or long-acting interferon? Generally short-acting interferon is observed for six months, if his HBV DNA can drop by two logarithmic levels, that is, by more than 100 times, if this standard is reached, the treatment will continue if there is a response. If the domestic interferon does not reach the standard in about six months, or even if the HBV DNA drops less than 100 times, we think the efficacy is not good, or the efficacy does not respond, the patient will change the drug. Similarly for long-acting interferon, if HBV DNA decreases by less than 100 times and E antigen does not decrease significantly, this is considered ineffective. Generally, long-acting interferon can decrease 10 to 100 times or more within six months, continue to use it for one year, and continue to do evaluation after one year, if it does not achieve a decrease of more than 100 times, it may stop. 10. Is there a preliminary result of the observation? From two aspects, the first HBV DNA, whether it is entecavir or telbivudine, when they use this class of drugs for primary treatment, the DNA conversion rate is 60% to 70% a year. The first is that the DNA conversion rate is 60% to 70% in one year when they use this class of drugs for initial treatment, while 100% of the DNA conversions are within three months when interferon treatment fails or is poorly treated patients switch to entecavir, and 100% of the conversions are within six months for telbivudine. The second is the problem of E antigen conversion, patients with major triplets, interferon treatment failure or poor switch to telbivudine about one year E antigen conversion can reach more than 50%, E antigen conversion into minor triplets, about 30% more, significantly higher than the initial treatment of domestic and international data. Entecavir also achieved an E antigen conversion rate of about 15%, which was not significantly different from the initial treatment, but improved the HBV DNA conversion rate. These results are still very encouraging. That’s why I say that I am now confident that there is a response to treating patients with either scripture. 11, Interferon treatment is not effective and switching to telbivudine can achieve higher E antigen conversion and conversion rates than switching to entecavir? Yes, compared to the same group, the E antigen conversion rate and conversion rate seems to be higher with telbivudine and higher than with primary treatment telbivudine because of the poor effect with interferon and actually in patients with refractory chronic hepatitis B. Achieve this effect, both from the patient’s point of view, or the doctor’s point of view are happier. 12. Is there any clinical situation where interferon treatment is not effective and anti-nucleoside analogs are added to this drug? Yes. Usually, Adefovir is added.