Antiviral therapy is the key to eradicating hepatitis B. In the past, because there were no effective antiviral drugs, the treatment of hepatitis B has been centered on “liver protection and enzyme reduction”. It was only in recent years that antiviral therapy was officially launched with the availability of interferon and antiviral nucleoside analogues. The clinical practice of antiviral therapy over the past few years has indeed allowed some patients to achieve long-term or short-term remission 医学教育网收集整理 . However, with the promotion of the application of antiviral drugs, some clinical problems have gradually emerged, making it necessary for us to think more deeply about the clinical value and use of antiviral drugs. First, the difficulty of antiviral treatment in the past few years, the widespread use of anti-hepatitis B virus drugs make us realize that, with the current drug effect, a complete cure for hepatitis B is still impossible. The main reasons for this are the following: (1) most of our chronic hepatitis B patients are perinatally infected, is that patients have varying degrees of immune tolerance, the body has never been able to establish a complete immune clearance function. Even after the immune tolerance is broken, it only manifests as an incomplete immune clearance accompanied by hepatocyte destruction. Cases that eventually lead to complete clearance of the virus, resulting in HBsAg/anti-HBs seroconversion, are rare. There are reports of patients with natural conversion of HBsAg in chronic hepatitis B with long-term follow-up who still have the presence of hepatitis B virus in the serum or liver tissue after many years and do not have an improved prognosis, and still have cirrhosis. (2) Covalent closed-loop DNA (cccDNA) of hepatitis B virus in hepatocytes is difficult to remove; cccDNA is the replicative form of the virus, which exists in relatively stable amounts in the nucleus of hepatocytes, and all current antiviral drugs cannot act directly on cccDNA, and when the virus is suppressed by drugs or the host immune system for a long time, the cccDNA pool can be gradually reduced because it cannot be The cccDNA pool can be progressively reduced but not completely depleted when the virus is suppressed by drugs or the host immune system for long periods of time. The cccDNA pool is replenished when antiviral therapy is discontinued or when the virus replicates again when the host immune system is depressed. Only the host’s immune system can completely remove cccDNA. When the host’s immune system is in a state of varying degrees of immune tolerance, it is unlikely that cccDNA will be completely cleared. The majority of patients with chronic hepatitis B will probably carry the hepatitis B virus for the rest of their lives. After the patient enters the immune damage phase, the severity of liver damage is often positively correlated with the level of viral replication. Antiviral therapy can reduce the level of viral replication and thus indirectly improve liver biochemistry and histology. In cases of long-term clinical remission, viral replication remains low, hepatocyte degeneration and necrosis are reduced, fibrosis is reduced (partially reversed), and patients have an improved quality of life and longer life expectancy. However, it is almost impossible to obtain a lifelong remission by a one-time antiviral treatment. A rebound in viral load and liver biochemistry often occurs after discontinuation of antiviral drugs, a phenomenon mainly caused by the loss of drug inhibition of the virus and its reactive replication, and the rebound phenomenon leads to the liver undergoing another destruction and progression of fibrosis, which is very detrimental to the liver. This is often the time when re-antiviral therapy is required to obtain remission. Therefore, since the hepatitis B virus is long term, antiviral therapy should also be long term. If the virus returns to active replication with liver damage after discontinuation of the drug, another antiviral treatment will be necessary and urgent. Viral YMDD mutation after lamivudine treatment is a common phenomenon in nature and is necessary for the evolution of the species. Hepatitis B virus gene mutation can occur in the natural state or after antiviral drug treatment. The YMDD mutation that occurs after lamivudine application is a drug-resistant mutation, but laboratory data demonstrate that the replication capacity of the YMDD mutant strain of the virus is reduced. Clinically, patients with YMDD mutations tend to have lower levels of HBV DNA replication than before treatment. This is often accompanied by an elevated ALT. However, there are some patients with high levels of HBV DNA replication after YMDD mutation. It is well documented that if lamivudine is continued after YMDD mutation, the disease may continue to improve and HBeAg/anti-HBe seroconversion may still occur, but the rate of conversion is lower than that of patients without mutation. There are reports of more HBeAg/anti-HBe seroconversion in patients with exacerbations than in those without exacerbations after YMDD mutations, but there are also patients who enter the hepatic decompensation phase after exacerbations, which deserves attention. If lamivudine is discontinued after YMDD mutation there is a risk of a sudden exacerbation, which may be related to the recovery of the wild strain. After discontinuation of lamivudine, the YMDD variant may disappear spontaneously and revert to the wild strain after about 4-6 months. If the disease worsens after the occurrence of YMDD mutation or after the discontinuation of the drug, it is important to closely observe the disease and intensify liver-protective therapy. In addition to lamivudine, other antiviral drugs that are effective against YMDD mutant strains, such as adefovir and entecavir, can also be used or added. Adefovir has been marketed abroad, and a 1-year phase III clinical trial is underway in China, and it is expected to be marketed in China within two years. In conclusion, viral genetic variation is a common phenomenon, and drug resistance variation is not terrible. After the emergence of drug-resistant mutation of the virus, it is necessary to strengthen the observation of patients to prevent the deterioration of the disease. The fear of viral mutation is unnecessary, and the fear of using antiviral drugs because of viral mutation is even more choking and delaying effective treatment. Fourth, interferon and lamivudine – limited role and limited indications currently available only two antiviral drugs interferon and antiviral nucleoside analogues and can not completely remove the hepatitis B virus infection. Lamivudine has few side effects and has a wide range of indications, but those with truly good efficacy for lamivudine and in line with pharmacoeconomic principles are mainly patients with active viral replication with markedly elevated ALT and in the active phase of liver inflammation. virus carriers with chronically normal ALT and light patients with low viral replication are not indications. The efficacy of lamivudine can be increased with long-term use. However, drug resistance (mainly YMDD variants) also increases rapidly, with a parallel increase in both. Relapse of the disease can occur after discontinuation of the drug, or even exacerbation after discontinuation. Those who have not developed drug resistance can take the drug for a long time to obtain higher efficiency, and should not stop the drug at will. Compared with lamivudine, the efficacy of interferon is lower than that of lamivudine in terms of HBV DNA reduction and ALT normalization rate, and the HBeAg seroconversion is higher than that of lamivudine, and the HBeAg seroconversion can continue to increase after stopping the drug, and improve the long-term prognosis of patients and reduce the incidence of cirrhosis and hepatocellular carcinoma. Rebound after discontinuation of interferon is also common, as evidenced by an increase in ALT and an increase in HBV DNA levels, which in most patients improves spontaneously without special treatment and is accompanied by reclearance of the virus. Interferon has very significant adverse effects. It is common to see an increase in transient hepatocellular damage caused by immune activation at the beginning of treatment, and some patients discontinue the drug as a result. Loss of hepatic impairment is a contraindication to the use of interferon, and hepatitis B virus carriers are also unsuitable for interferon therapy with poor efficacy. In conclusion, each of the two types of antiviral drugs has its own indications, the appropriate application can expect better results, but non-indicated patients use half the effort, a waste of resources, and may even endanger the lives of patients.