The guidelines for the treatment of chronic hepatitis B in both Europe and the Asia-Pacific region and in China clearly state that the primary treatment goal for chronic hepatitis B is to prevent the development of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and ultimately to prevent death associated with hepatitis B virus infection. The causative factor of chronic hepatitis B is the hepatitis B virus, so controlling the hepatitis B virus naturally becomes a key factor in controlling the progression of hepatitis B. It is also the basis for achieving the main therapeutic goal of chronic hepatitis B. The current anti-hepatitis B virus drugs mainly include interferon and nucleoside analogues, both of which can effectively control the replication of the virus, especially the nucleoside antiviral drugs have a strong inhibitory effect on HBV DNA replication, such as telbivudine and entecavir used for 48 weeks, the intensity of HBV DNA inhibition can reach more than 6 exponential levels (i.e. HBV DNA decreases by more than 6 log copies/ml). HBV DNA is integrated in the nucleus of liver cells in the form of cccDNA (covalent closed-loop DNA), and the clearance of HBV cccDNA takes an average of 14.2 years, so adherence to treatment is the key to maintaining antiviral efficacy, and adherence to a full course of treatment reduces the chance of viral resistance and relapse. But can adherence to treatment be equated with lifelong treatment? There are approximately 120 million HBV carriers in China, of which about 30 million are chronic hepatitis B patients. So how scary is chronic hepatitis B? Technically speaking chronic hepatitis B is not as scary as we think it is. Diseases that require lifelong treatment First, let’s recognize what kinds of diseases require lifelong treatment. It is generally accepted that diseases that meet the following three criteria require lifelong treatment: 1) the disease will progress progressively without targeted treatment; 2) the causative agent cannot be eliminated by itself or the disease is basically irreversible; 3) the disease will relapse and progress soon after the disease is stabilized by stopping the targeted medication, and there will be no sustained response to treatment. Common diseases that meet these three conditions are hypertension, primary diabetes and AIDS. Does chronic hepatitis B require lifelong treatment? We have seen that the guidelines for antiviral treatment of chronic hepatitis B developed around the world have appropriate discontinuation criteria. The chronic hepatitis B treatment guidelines developed in China set the discontinuation criteria for nucleoside analog therapy as follows: after completing 1 year of basic therapy, HBeAg positive patients with undetectable HBV DNA and HBeAg serologic conversion can discontinue the drug after monitoring 2 times (each at least 6 months apart) and still remain unchanged and with normal ALT. In HBeAg negative patients, the drug can be discontinued when HBV DNA is undetectable after 3 times of monitoring (at least 6 months interval each time) when HBV DNA is undetectable (PCR method) or below the lower limit of detection and ALT is normal. Therefore, chronic hepatitis B is not yet a disease requiring lifelong treatment and is reversible in 2% of patients each year. The 2009 European guidelines for liver disease (EASL guidelines) further specify that HBeAg-negative patients, HBeAg-positive patients who have not acquired HBeAg seroconversion, and patients with cirrhosis (including those who have developed HBeAg seroconversion) should receive long-term treatment. At the same time, the EASL guidelines also clarify the concept of limited therapy, the applicable population and the indications for discontinuation: HBeAg seroconversion is the goal of limited therapy with nucleoside analogs, and studies have shown that nucleoside analogs can be discontinued after 24 weeks to 48 weeks of continued therapy if HBeAg seroconversion is achieved under conditions of undetectable HBV DNA. The treatment can be discontinued after 24 weeks to 48 weeks of continued treatment. The “double target” antiviral concept is therefore particularly important for HBeAg-positive patients with chronic hepatitis B. What is the “double target” antiviral treatment? What is the “double target” concept of antiviral therapy? It means that after using antiviral therapy, HBV DNA quantification decreases to undetectable levels and HBeAg serological conversion is achieved at the same time, that is, the patient’s serum monitoring HBeAg changes from positive to negative and anti-HBe appears. Currently, four nucleoside antiviral drugs are available in China: lamivudine, adefovir, telbivudine and entecavir. Entecavir has a strong HBV DNA inhibition effect and low resistance rate, but the HBeAg seroconversion rate of the drug is low, so the chances of reaching a satisfactory endpoint and stopping the drug are low for HBeAg-positive patients. The best drug that has been shown to achieve a satisfactory “double target” is telbivudine, especially for pre-treatment HBV DNA