The first strategy: immune-based interferon alfa therapy, after a limited course of treatment (6-12 months, a few up to 18 months), to achieve a durable response after discontinuation of the drug, with disappearance of HBeAg and a durable serological conversion of Anti-HBe to positive; a few patients may also achieve a true cure with disappearance of HBsAg and conversion of Anti-HBs, although this depends on some Although this depends on some luck and cannot be the main goal, a few people do achieve it. The second strategy: use nucleoside analogs and take them for a long time to achieve a maintenance response for the duration of the drug (this means that once the nucleoside analogs are started, they cannot be stopped easily, let alone without the doctor’s permission, or there is a risk of deterioration of liver function. HBV DNA will rebound to higher levels than before treatment). However, long-term drug use poses another serious problem, which is the mutation of the virus. There are now a growing number of clinical studies showing that viral mutation is followed by reactivation of liver inflammation and fibrosis, and in a few patients, even deterioration of liver function. Interferon should not be used unless there are contraindications to interferon. For example, history of psychiatric disease or family psychiatric history, severe depression, allergy to interferon or a component of interferon, pregnancy, severe autoimmune disease, cirrhosis loss (i.e., symptoms of cirrhosis such as ascites), too low white blood cells or platelets, etc. Otherwise, as long as the patient has elevated ALT, positive HBV DNA, no jaundice, and has entered the immune clearance phase, interferon alfa therapy should be considered first. This is the current view of the absolute majority of hepatitis B experts in China, a conclusion reached by Chinese hepatologists after years of experience and lessons learned, and a conclusion drawn from many failed and even fatal cases after summing up years of lamivudine abuse. Back in 1998, when lamivudine was marketed, it was sold like crazy for a while because of its convenience of oral administration and fast reduction of serum HBV DNA, and the inexperience and lack of sufficient knowledge of it among doctors and patients in China. Even some large and small pharmacies are selling this prescription drug that should only be available in hospitals. There are even small grassroots hospitals, even fatty liver, hepatitis C and other unrelated liver diseases are used lamivudine. As if lamivudine is the miracle drug for liver disease. This shows how serious the abuse of lamivudine was at that time. In 2000, Nance Leung from Hong Kong reported a case of liver function deterioration, liver necrosis and patient death after lamivudine was stopped. Since then, several cases of hepatic necrosis and deterioration of liver function due to improper discontinuation of lamivudine have been reported in China. Only then did the hepatologists understand what this drug was and that it was not as miraculous as they had imagined. Not only did the drug fail to cure hepatitis B, but it caused all sorts of problems with long-term use of the drug. The incidence of virus mutation kept appearing, and more and more patients became sicker after stopping the drug. In Chengdu, Shanghai, Hangzhou and other places, there were cases of patients suing Glaxo for death after stopping lamivudine. After nearly 8 years, Chinese hepatologists finally understand that nucleoside analogs can no longer be abused. Not just lamivudine, but all nucleoside analogs should be used with caution. No matter how strong the new nucleoside analogs are in reducing HBV DNA and how fast the serum HBV DNA turns negative, most of them will still relapse after stopping the drug. Most of the long-term medications will develop mutations and resistance at different times. The treatment of chronic hepatitis B in Chinese people is characterized by long-term, arduous and complex nature. This is mainly due to the fact that most Chinese people with chronic hepatitis B have vertical mother-to-child transmission, where the patient is infected at birth or at a very young age, and is in a very strong immune tolerance state, where for 10-20 years, or even longer, the patient is in the immune tolerance period, and their own immune system has no immune response to hepatitis B virus. For the hepatitis B virus that has survived for so long in the body, and the body has no immune recognition and clearance of it, it is difficult to imagine what magical methods we can use to wipe out the virus and remove it from the body in a short period of time. You must be prepared to do battle with the virus for a long period of time and never be in a hurry. This is exactly what we often say, the freezing of three feet is not a day’s cold, and the thawing of the frozen ice for a long time can not be achieved overnight. Another reason for the difficulty in treating hepatitis B in China is that hepatitis B in China is predominantly type C hepatitis B, which may account for about 70% of the cases in Shanghai. The long-term and arduous nature of hepatitis B treatment dictates that both hepatologists and hepatitis B patients themselves must take it seriously and must think strategically before making a decision. This is because, after a decision is made, the results of that decision will not be seen in a day or two, but in a year, two years or even longer. How can a decision be taken lightly for such a long, time-consuming, labor-intensive, and financially-draining “task”! That’s why hepatitis B experts have come up with two strategies for hepatitis B treatment when deciding which drug to choose. This is not my creation, but a summary of years of experience by renowned scholars and experts in China, the consensus of the most mainstream experts and scholars in China. It should be noted here that the above two strategies mainly focus on the beginning of the treatment phase, and during the initial treatment, if interferon can be used, nucleoside analogues are not used as much as possible. However, in terms of overall antiviral activity, the two strategies are not antagonistic or contradictory, and should be complementary if applied well in clinical practice. After all, there are still many patients for whom interferon therapy is also ineffective. Interferons and nucleoside analogs are fundamentally different and act on completely different principles. Sometimes doctors will take different combinations of interferon and nucleoside analogs to achieve maximum control of the virus, depending on the patient’s condition. But it is even more complicated as to how to make the combination, and everyone may have a different point of view, which is why patients can go from one hospital to another, and from one doctor to another, with completely different treatment plans, or even completely opposite plans. It often baffles the hepatitis B patient. Why are there so many patients on nucleoside analogs now? One of the main reasons is that nucleoside analogs, such as lamivudine, adefovir, entecavir, etc., are administered orally and have fewer side effects than interferon during dosing. The second reason is that most of the nucleoside analogs, except lamivudine, are new drugs, which are more interesting and easily attract the attention of doctors and patients. Another more important reason is that nucleoside analogs reduce serum HBV DNA quickly, and patients’ serum HBV DNA turns negative soon after taking the drug. This temporary and rapid conversion of HBV DNA is very attractive to doctors and patients alike. Finally, the cost of nucleoside analogs for one year is cheaper compared to interferon, especially the imported interferon. For these reasons, many uninformed patients easily make the decision to choose nucleoside analogs first, without considering what will happen a year, two years, or three years later. No consideration is given to the fact that once a nucleoside analogue is used it cannot be easily stopped or it may have serious consequences. There is no consideration of the variability of long-term use of nucleoside analogs and relapse after discontinuation of the drug. It is difficult for the patient to distinguish which of the two drugs should be preferred if the doctor does not have the patience or much time to explain to the patient? Interferon is a multifunctional protein produced in the body in response to viral infections and has multiple functions including antiviral, enhancing hepatitis B specific immunity and anti-fibrosis. Although the direct antiviral power of interferon is weak, its ability to improve the body’s recognition of the hepatitis B virus and enhance the specific immune function against the hepatitis B virus is critical to achieving a durable response after drug discontinuation. In contrast, nucleoside analogues can only temporarily inhibit the synthesis of HBV DNA in the cell plasma, not through immunity, so no matter how fast it reduces serum HBV DNA, it cannot fundamentally control the virus in the long term, and must be taken for a long time to achieve a maintenance response during the drug, and most of them will relapse after stopping the drug, and the previous work will be abandoned. However, the biggest problem of long-term drug use is the mutation of the virus and drug resistance. After understanding the mechanism of action of the two drugs, it is easy to understand why interferon must be preferred to interferon, only interferon can not be used, or multiple treatment failure before considering nucleoside analogues. Although nucleoside analogs can achieve a temporary HBV DNA decline faster or disappear, and the new entecavir down the virus much faster than lamivudine, but in essence, no matter how fast the speed of decline, the final result is not much the same. This is because they work on the same principle. Although HBV DNA drops quickly, the seroconversion rate at one year of treatment is not significantly different from lamivudine. In addition to its direct antiviral effect, the main effect of interferon alfa is to strengthen the body’s immune recognition of the hepatitis B virus and enhance the clearance of infected liver cells by lymphocytes. The activation of a type of lymphocyte called CD8+ recognizes the infected hepatocytes, lyses and destroys them, and removes the CCC-DNA along with them. This response, obtained by immune activation, is mostly longer lasting after drug discontinuation. Nucleoside analogs only inhibit HBV DNA synthesis within the cells and have no effect on human immunity, and cannot clear CCC DNA by activating immune function. This kind of virus that only inhibits intracellular plasma mostly relapses after stopping the drug and must be used for a long time without interruption.