Antiviral is an important breakthrough in the treatment of slow hepatitis B. In the 2006 edition of the Chinese Medical Association’s Guidelines for the Prevention and Treatment of Chronic Hepatitis B, the overall goal of the treatment of slow hepatitis B is to “maximize long-term suppression or elimination of HBV, reduce hepatocellular inflammatory necrosis and liver fibrosis, delay and stop disease progression, and reduce and prevent liver decompensation, cirrhosis, hepatocellular carcinoma and their complications, thereby improving quality of life and prolonging life.” The overall goal set by the guidelines is a very realistic and scientific formulation, as HBV antiviral therapy to date has been able to inhibit viral replication and induce remission of liver disease to some extent. After the release of the guidelines, physicians, including those in the author’s unit, studied them carefully and actively administered antiviral therapy to patients with chronic hepatitis B according to the guidelines’ advice, with promising results. However, the recognized effective drugs such as interferon and various nucleoside (acid) analogues have not been able to solve all the problems in clinical practice as much as one would expect. Among patients with HBsAg-positive chronic hepatitis spontaneous or HBsAg-negative by antiviral therapy, 28% to 94% have HBVDNA in the serum and liver, which is not only seen in patients with chronic liver disease, but also in blood donors without evidence of liver damage, such HBsAg-negative serum is infectious and can cause post-transfusion hepatitis and mother-to-child transmission, and patients with cirrhosis Reasons for HBsAg-negative but still positive HBVDNA include: viral mutation; rearrangement of surface genes after viral integration or antigenic changes in virally expressed proteins; insufficiently sensitive HBsAg detection techniques; antigens hidden in HBsAg complexes; viral integration into liver tissue ; exogenous factors such as alcohol, co-infection with hepatitis C virus, etc., interfere with HBV antigen expression. Patients with pre-existing cirrhosis can have complications such as portal hypertension despite biochemical and virological responses after treatment. It has been found that there is no difference in the incidence of complications of cirrhosis between control and interferon-treated groups, or between HBeAg-negative or non-negative. Even in HBsAg-HBsAb seroconverters, HBV can be reactivated if immunosuppression is caused by chemotherapy or organ transplantation, and HBV is still present in extrahepatic tissues (lymph nodes) and extrahepatocellular (bile duct cells) reservoirs. The effect of anti-HBV treatment is still unsatisfactory and cannot completely remove the virus for the following reasons: viral factors: the half-life of HBV in the serum is about 24 hours, about 100 billion viruses are released from the liver every day, and the half-life of HBV infection of hepatocytes is 10-100 days. HBVDNA uses cccDNA as the original template for replication during the replication process, and cccDNA has a long half-life and It is not easy to degrade naturally, and the current antiviral drugs have no effect on cccDNA. Once the drugs are stopped, cccDNA can be used as a template for HBV replication and re-transcriptional replication, which becomes an important cause of relapse. Under drug pressure, hepatitis viruses such as HBV and HCV are prone to mutation, and mutated viruses are often resistant to antiviral drugs or have poor efficacy, such as HBV pre-C region and C region promoter mutant strain infections, which are poorly treated with interferon. YMDD mutant strain infections after lamivudine treatment can develop drug resistance, etc. In addition to liver parenchymal cells, HBV replicates in other tissues such as bile ducts, pancreas, and lymphocytes, and current antiviral therapy has no effect on HBV in these sites; HBV proliferates continuously using its structural and nonstructural proteins, which can evade human immunological intervention; HBV forms a stable transcriptional template outside the host chromosome and can adapt to subtle changes in the microenvironment to regulate its transcriptional HBV forms a stable transcriptional template outside the host chromosome and can adapt to subtle changes in the microenvironment to regulate its transcript levels. Most patients often have a history of chronic HBV infection for decades prior to HBsAg clearance, and the chronic hepatic damage or viral integration within liver tissue caused by such infection may be the primary mechanism leading to cirrhosis and hepatocellular carcinoma, and the development of these complications may be unrelated or rarely associated with HBVDNA itself. Host factors: patients with varying degrees of immune tolerance, this group is defined as patients with hepatitis B with normal alanine aminotransferase, high titers of HBeAg, HBVDNA >105 copies/ml and mild inflammatory changes in liver histology. HBV cannot be cleared immunologically or poor drug efficacy favors long-term virus retention and replication in the body. Studies of the genetics of chronic hepatitis B suggest that there may be defects and differences in expression of susceptibility-related genes and interferon signaling systems. HBVDNA can integrate with the host cell chromosomal DNA and the integrated HBVDNA is not easily cleared by antiviral drugs. Most cases of hepatitis B in China come from vertical transmission from mother to child. Patients with hepatitis B are infected with HBV at a young age (some are infected in utero) and become chronic carriers of the virus, often due to genetic and racial characteristics that determine susceptibility to hepatitis B and the long-term nature of hepatitis B. When infected with HBV at a young age, the body’s immune system is not well developed and cannot recognize the virus. The gradual integration of HBV with hepatocytes, the high immune tolerance state of the organism and the multiple genetic integration that occurs between HBV deoxyribonucleic acid and hepatocytes determine the difficulty and enormity of hepatitis B treatment. There is no effective antiviral therapy for slow hepatitis B with normal transaminases. Both alpha interferon and various nucleoside analogs have elevated transaminases as an indication for treatment, while asymptomatic “carriers” with normal serum transaminases have no significant effect with existing antiviral therapy and are therefore generally not targeted for antiviral treatment. However, normal transaminases do not necessarily mean normal liver tissue structure, and it is not uncommon for cirrhosis and hepatocellular carcinoma to occur in these cases, and those who have had cirrhosis and hepatocellular carcinoma do not necessarily have elevated transaminases in their medical history. It is currently believed that the best time for antiviral treatment of hepatitis B is when liver inflammation is present and aminotransferase levels are elevated, but for the many patients with current hepatitis B infection, few fit this profile. Contraindications to antiviral therapy are numerous and many patients do not tolerate it. On top of antiviral basis, emphasis on anti-fibrotic treatment liver fibrosis is a common pathway for the development of various chronic liver diseases including slow hepatitis B. It is also a necessary pathway to further development of irreversible liver cirrhosis. The development process of chronic hepatitis B is closely related to the proliferation of fibrous connective tissue. As the disease progresses, the ECM in the liver increases progressively, collagen tissue forms in large quantities, extends into the liver lobules, invades the liver parenchyma, closes in the confluent area, forms fibrous septum, liver blood circulation is destroyed, hepatocytes become degenerative and necrotic, regenerative liver nodules are formed, and reaches the degree of cirrhosis, so interrupting the formation and development of liver fibrosis is also the way to prevent Therefore, blocking the formation and development of liver fibrosis is also an inevitable part of preventing the development of liver cirrhosis. The activation of hepatic stellate cells (HSC) is the core event of liver fibrosis, and there are two pathways of HSC activation: one is the synthesis and secretion of a series of cytokines by hepatocytes, Kupffer cells and endothelial cells, which are stimulated by pathogenesis to synthesize extra cellular matrix (ECM). matrix (ECM), which is called the “paracrine pathway”; second, HSC activation synthesizes various cytokines and further activates itself, which is called the “autocrine pathway”, and once the autocrine pathway is open, even without further stimulation from the etiology, liver fibrosis can still Once the autocrine pathway is open, liver fibrosis can still progress actively even without further stimulation from the cause. Therefore, etiologic and primary treatment is not a complete substitute for anti-fibrotic therapy. The founder of modern hepatology, the late Professor Hans Popper, a leading authority on hepatology, clearly stated that “whoever can stop or delay liver fibrosis will be able to cure most chronic liver diseases.” The discovery of HSC activation provides an important network to identify the point of action of anti-fibrotic therapies. These therapies include: 1. treatment of the primary disease to prevent injury; 2. attenuation of inflammation or host response to avoid stimulation of hepatic stellate cell activation; 3. direct downregulation of stellate cell activation; 4. counteracting stellate cell proliferation, fibril formation, contraction, and/or response to inflammation; 5. stimulation of stellate cell apoptosis; 6. stimulation of metallo-matrix protease production by cells, downregulation of metallo-matrix protease inhibitors, or direct administration of metallosubstrate proteases to increase degradation of the extracellular matrix. The process of reversal of liver fibrosis involves the degradation and remodeling of collagen, a major component of the ECM, and the eventual return to a normal liver structure. The most central issue in this process is the significant reduction or elimination of excessive, activated HSC numbers. Apoptosis of activated HSC is central to the reversal of liver fibrosis, and none of the existing HBV antiviral drugs have this pharmacological effect. The hallmarks of successful reversal of liver fibrosis are: effective control of the inflammatory response and inhibition of mediator activation of hepatic stellate cells; regulation of hepatic stellate cells and reduction of extracellular matrix gene transcription; and improvement of collagenase activity and levels in liver tissues to promote lysis and absorption of collagen tissue. The completion of each of these therapeutic goals is a rather lengthy process, which predetermines that anti-liver fibrosis treatment cannot be achieved overnight. Anti-viral therapy and anti-fibrotic therapy are not substitutes for each other, but rather complementary and mutually reinforcing. Anti-fibrotic therapy can play a synergistic role with antiviral therapy, and the two complement each other, which is conducive to the suppression and clearance of the virus, as well as the improvement and repair of liver tissue pathological damage, delaying or preventing the formation of cirrhosis.