Over the past 10 years, substantial progress has been made in the treatment of chronic hepatitis B. The treatment has evolved from liver-protective and enzyme-lowering therapy in the past to a comprehensive treatment based on antiviral therapy, which has led to sustained stabilization and no further disease progression, enabling the maintenance of normal work and life; some patients with hepatitis B cirrhosis have even experienced an unexpected improvement (reversal to the good side) and a significant improvement in quality of life. With the introduction and continuous updating of the guidelines for the prevention and treatment of chronic hepatitis B at home and abroad, the concept of antiviral treatment has been popularized in China. However, there are also some phenomena of unreasonable treatment, such as over-treatment and miscarriage of treatment. So what is rational treatment? The so-called rational treatment is to select effective drugs suitable for patients at the right time for antiviral treatment and to monitor the treatment response in a standardized manner. We fully absorb and understand the domestic and international guidelines for chronic hepatitis B and summarize the experience accumulated in our clinical practice, and talk about the rational treatment of chronic hepatitis B. I. When to start antiviral therapy The natural course of chronic HBV infection is generally divided into the immune tolerance period, immune clearance period, inactive period and reactivation period, the immune tolerance period and inactive period generally do not require antiviral therapy because of the small damage to the liver and low risk of adverse clinical outcomes; antiviral therapy is mainly applied to patients in the immune clearance period and reactivation period. Given that current antiviral therapy mainly suppresses the virus but does not eradicate it, and has limited long-term efficacy, and mostly requires adherence to long-term therapy, the timing of treatment should be chosen more carefully. Before deciding to initiate or delay antiviral therapy, careful consideration must be given to the patient’s age, condition, efficacy, and potential adverse effects of the drug; a thorough evaluation of the condition to clarify the disease stage and HBV replication status; and evaluation and prediction of the risk of cirrhosis and hepatocellular carcinoma in the foreseeable future, as well as the likelihood of spontaneous remission of the disease. General indications for antiviral therapy: mainly refers to HBeAg-positive chronic hepatitis B entering the immune clearance phase and HBeAg-negative chronic hepatitis B entering the reactivation phase. According to the new version of China’s guidelines for the prevention and treatment of chronic hepatitis B, (1) HBeAg-positive patients with HBV DNA ≥105 copies/ml (equivalent to 2000 IU/ml); HBeAg-negative patients with HBV DNA ≥104 copies/ml (equivalent to 2000 IU/ml); (2) ALT ≥2×ULN (high value of normal); if treated with interferon, ALT should be ≤ 10 × ULN and total serum bilirubin should be <2 × ULN; (3) ALT <2 × ULN, but liver histology shows obvious inflammatory necrosis or fibrosis. According to the relevant foreign guidelines and our experience, immediate antiviral therapy is needed for the following patients: (1) patients with liver failure and decompensated cirrhosis associated with HBV infection, these life-threatening severe liver diseases, as long as HBVDNA can be detected, should be immediately given nucleoside (acid) analogues to help stabilize the disease and improve survival, and also reduce the fraction risk of postoperative hepatitis B recurrence in liver transplant patients (more pros than cons). (2) Patients with compensated cirrhosis should be actively treated with antiviral therapy due to the high risk of serious complications in these patients (our guidelines stipulate that the indication for treatment is HBV DNA ≥104 copies/mL for HBeAg-positive patients and HBV DNA ≥103 copies/mL for HBeAg-negative patients, regardless of whether the ALT is elevated). There has been reliable evidence-based medical evidence that antiviral therapy not only stops disease progression and reduces the risk of serious complications, but also shows an unexpected reversal effect in some patients, bringing a boon to patients. (3) HBsAg-positive patients receiving oncologic chemotherapy and immunosuppressive therapy, who are at risk of causing acute exacerbation of hepatitis B, should also be treated with prophylactic antiviral therapy prior to initiation of therapy. We have seen several cases where antiviral therapy was neglected, thereby inducing hepatitis activity and severe hepatitis. Priority targets: (1) HBeAg-positive older patients (in their late 30s or early 40s) still without spontaneous HBeAg serologic conversion and with significant active inflammation and fibrosis (with indications for antiviral therapy), prone to develop hepatitis B cirrhosis, should be given effective antiviral therapy, which mostly stops or delays disease progression. (2) HBeAg-negative chronic hepatitis B, mostly patients in the reactivation stage, should be given antiviral therapy if they have indications for hepatitis B antiviral therapy. (3) Patients with chronic HBV carriers (characterized by HBsAg positive, HBeAg positive or negative, HBV DNA positive, and normal ALT) who are older (>40 years old), especially males or those with a family history of HCC, should be followed closely and dynamically observed for ALT changes or evidence of disease progression (e.g., enlarged spleen), and liver histology is strongly recommended with the aim of timely detection of partial conversion from carriers to hepatitis B patients and aggressive antiviral therapy. Patients who do not require antiviral therapy for the time being: (1) younger HBeAg-positive chronic hepatitis B, especially patients with initial hepatitis exacerbations, who have a low risk of cirrhosis and hepatocellular carcinoma in the foreseeable future and have the potential for spontaneous HBeAg seroconversion and are not given antiviral therapy for the time being (both the US guidelines and the latest Asia-Pacific guidelines recommend 3 to 6 months of observation), unless there is evidence of indicates the presence of progressive liver disease. If spontaneous seroconversion of HBeAg occurs, antiviral therapy may be omitted. Patients with high transaminase levels (≥10×ULN) should be carefully analyzed based on prothrombin time and bilirubin levels and given antiviral therapy promptly if they are predisposed to severe hepatitis; if prothrombin time and bilirubin levels are not high, they should be temporarily observed and, in our clinical experience, a significant proportion of patients will obtain spontaneous seroconversion and enter the inactive phase, where antiviral therapy can be delayed or avoided. Antiviral therapy can be delayed or avoided, reducing the burden on patients and saving medical resources. (2) Inactive HBsAg carriers (characterized by HBsAg positivity, HBeAg negativity, HBV DNA negativity, and normal ALT) do not require antiviral therapy under general circumstances. (3) Chronic HBV carriers in the immune tolerance period are also not suitable for antiviral therapy (fewer benefits and more drawbacks), so it is not recommended by the Domestic and International Guidelines. At present, there are still some medical institutions in the market, driven by interests, through a large number of false and inaccurate propaganda, blind treatment of these patients in the tolerant and inactive stage, so that patients spend a lot of money in vain. The treatment of hepatitis B today has entered the era of “multi-drug competition”, and patients are prone to many confusions while having more choices. There are currently seven types of antiviral drugs (interferon and nucleoside analogs) used in the regular treatment of chronic hepatitis B, namely: common interferon a, pegylated interferon a, lamivudine, adefovir, entecavir, tipifudine and tenofovir. Evaluated objectively in a scientific manner, these are hard-won and effective drugs that have been studied by evidence-based medicine and widely used clinically, but they are also not yet ideal drugs. Interferon has the advantages of high HBeAg and HBsAg seroconversion rate and limited treatment course, but the antiviral efficacy and adverse effects are obvious; nucleoside analogues have the advantages of strong antiviral effect, oral administration and good tolerability, but easy to relapse after discontinuation of the drug and need long-term treatment. Each of these drugs has its own characteristics, and only if applied properly, more than satisfactory results can be obtained. The key is that the doctor should put the patient’s interests in the highest position in his heart and do everything for the patient; the patient should cooperate with the doctor to reasonably choose the most suitable drug for his long-term treatment according to his financial ability and adhere to the standardized and optimal treatment. According to the spirit of the new guidelines and our experience, younger patients (<30 years old), especially women of childbearing age, who prefer interferon therapy, may complete the treatment phase within a limited course (six months to one year) and achieve a high HBeAg serological conversion target; if they choose the optimal treatment regimen of tibivudine for HBeAg-positive chronic hepatitis B, they may also achieve viral suppression and HBeAg conversion more quickly. The "double target" of viral suppression and HBeAg conversion may also be achieved more quickly with the optimal treatment regimen of telbivudine for HBeAg positive chronic hepatitis B. Middle-aged patients (30-50 years old), especially those with HBeAg-negative chronic hepatitis B, can be treated with entecavir, which is less resistant, if available, to facilitate safe long-term treatment; those with low viral load can also be treated with adefovir, which also has a lower resistance rate for long-term treatment. In older patients (over 50 years old), especially those with hepatitis B cirrhosis, if lamivudine-based optimal therapy is chosen, and if adefovir combination therapy is added early or in advance for patients with poor efficacy and resistance tendency, or if lamivudine and adefovir combination therapy is chosen for the initial treatment of patients with high viral load, it may effectively prevent or delay the occurrence of drug resistance and safely carry out long-term treatment. In short, in China, the above-mentioned seven are first-line drugs, from a practical point of view, while considering the affordability of patients from the perspective of long-term treatment, choose the right drug for patients. As Minister Chen Zhu pointed out, "develop a standardized treatment plan that reflects both the technical content and is compatible with the existing national power, basic medical affordability and the economic ability of the masses, so that the masses can really benefit from it". Standardized efficacy monitoring The efficacy monitoring of interferon should be done by testing serum HBVDNA levels at 12 and 24 weeks to observe the early antiviral response. European guidelines for the prevention and treatment of hepatitis B suggest that if serum HBVDNA load decreases less than 1 log (log) value from baseline after 12 weeks of interferon treatment, it is defined as primary non-response, and the long-term efficacy of such patients is also poor, and interferon treatment should be discontinued and replaced with nucleoside (acid) analogues to reduce unnecessary waste. The current study found that changes in HBsAg and HBeAg titers are more useful in predicting the long-term efficacy of interferon therapy. Monitoring the efficacy of nucleoside (acid) analogs Monitoring of nucleoside (acid) analogs after treatment of chronic hepatitis B can be done by applying the roadmap concept. The concept of roadmap for nucleoside (acid) analogs in the treatment of chronic hepatitis B was proposed by Keeffe et al. in 2007. The core of the concept is to monitor regularly during the treatment process, evaluate the safety of the drug, patient compliance and treatment response based on the monitoring results, predict the long-term efficacy, and evaluate, adjust and optimize the original treatment regimen and implement individualized treatment in order to improve the long-term treatment response rate and The aim is to improve long-term treatment response rate and reduce drug resistance. If, with good compliance, HBV-DNA decreases by less than 1 log IU/mL at 12 weeks or 2 log IU/mL at 24 weeks with nucleoside (acid) analogs, this is defined as primary non-response and the treatment regimen should be changed. （Patients with complete virological response (undetectable serum HBV DNA) at 24 weeks do not require treatment regimen adjustment. Partial virologic response (defined as a decrease in HBV DNA ≥2 log IU/mL from baseline at 24 weeks, but not below the lower limit of detection) should be treated with a combination of nucleoside (acid) analogs without cross-resistance sites as early as possible. Lamivudine, telbivudine or entecavir are chosen for initial treatment, and adefovir can be added for any poor response (in foreign countries, tenofovir is mostly chosen, with less relative risk of nephrotoxicity and the most potent viral suppression); lamivudine, telbivudine or entecavir can be added for poor response to initial treatment with adefovir. Domestic and international studies and our experience show that even with lamivudine or telbivudine, with optimized treatment, a proportion of patients are eventually non-resistant to long-term treatment and finally achieve their treatment goals, saving a considerable amount of treatment costs and avoiding the possible risks of combination drug use. Moreover, the efficacy of early combination therapy in patients with poor early (24 weeks) response, or even earlier (12 weeks) possible poor response, remained quite satisfactory. Therefore, the authors believe that this is a successful option that is better suited to the national and popular situation, at least today. Fourth, extending the course of treatment can consolidate the efficacy and reduce relapse The course of interferon analog therapy for chronic hepatitis B is generally 6 months (regular interferon) and 12 months (pegylated interferon), and can be extended to 1 year or longer, respectively, to improve the efficacy if there is a response. The basic course of treatment for HBeAg positive chronic hepatitis B or HBeAg recessive chronic hepatitis B requires at least 1 year, with the former requiring HBVDNA below the lower limit of detection, ALT normalization, and HBeAg serological conversion, and the latter requiring HBVDNA below the lower limit of detection and normal ALT. On this basis enter consolidation therapy, which remains unchanged for at least 1 year and more than 1.5 years (reviewed at 6-month intervals), respectively. A high proportion of patients who discontinue according to the above criteria still have recent relapses, so relevant guidelines emphasize that this is the minimum course of treatment and recommend appropriate extension to reduce relapses. European guidelines classify treatment endpoints as: ideal endpoint (persistent HBsAg disappearance with or without the appearance of anti-HBs antibodies), satisfactory endpoint (persistent HBeAg seroconversion) and sub-satisfactory endpoint (persistent undetectable levels of HBV DNA). The ideal endpoint has long-lasting efficacy and should not be relapsed, but only a very small number of patients achieve it, so it should not be pursued excessively, otherwise it may increase the unnecessary economic burden of patients; the satisfactory endpoint is more realistic and is a goal that HBeAg-positive patients can strive to achieve; the sub-satisfactory endpoint is the basic goal for HBeAg-positive patients who have not achieved HBeAg seroconversion and HBeAg-negative patients. According to the summary of our clinical practice, the courses of treatment are grouped into three categories: (1) limited courses, which are given to young patients as much as possible, otherwise long-term or lifelong treatment will bring heavy economic pressure and mental burden to patients. For young patients who achieve satisfactory or sub-satisfactory endpoints, the drug can be discontinued for observation after appropriate extension of the course of treatment. After discontinuation of the drug, HBVDNA index must be closely monitored and prior antiviral therapy can be given if viral rebound occurs. Especially for HBeAg-positive young patients, a limited course of interferon can be chosen, and also HBeAg seroconversion of higher tibivudine can be chosen, which is expected to achieve "double standard" and obtain satisfactory endpoints. (2) Long-term treatment, mostly for HBeAg-negative middle-aged patients, these patients may progress to cirrhosis and liver cancer, and nucleoside (acid) analogue treatment is easy to relapse, long-term treatment is recommended until HBsAg disappears. (3) Lifelong treatment, for elderly patients with Hepatitis B cirrhosis and hepatocellular carcinoma, current domestic and international guidelines mostly recommend lifelong treatment, with more advantages than disadvantages.