Antiviral therapy for hepatitis B virus-related liver failure Hepatic failure is a type of liver disease with a high mortality rate and a serious threat to people’s health, and hepatitis B virus (HBV) infection is still the main cause of liver failure in China. The role of adding antiviral therapy to traditional combination therapy is gaining attention, and a series of issues such as indications for antiviral therapy for HBV-related liver failure, how to select antiviral drugs and the timing of antiviral therapy are still hot spots and difficulties in the field of antiviral therapy. The pathogenesis of HBV-related liver failure is still not clear, but it is now recognized that both immunological and non-immunological factors play an important role; nowadays, special emphasis is placed on viral factors, and it is believed that the hyperactive immune response induced by the continuous replication of HBV in the body is the main pathogenic factor leading to massive hepatocyte necrosis. Antiviral therapy at an early stage of the disease is the first and crucial link to suspend the intense cellular and humoral immunity. Therefore, antiviral therapy has become a proven treatment for severe hepatitis B, as evidenced by the satisfactory efficacy of antiviral therapy with nucleoside analogs. HBV-related liver failure, as a special population, should be carefully selected when choosing the type of antiviral drug. Interferon has certain side effects and aggravates hepatic necrosis due to enhanced immune response and should be contraindicated in liver failure. With the continuous development of oral antiviral drugs and the large amount of evidence-based medical evidence and clinical practice experience they have accumulated in the antiviral treatment of chronic hepatitis B in the last decade, the use of antivirals for HBV-related liver failure has become an essential therapeutic measure in its treatment. Currently, the main antiviral drugs used for HBV-related liver failure are nucleoside (acid) analogues, including lamivudine (LVD), adefovir (ADV), telbivudine (LDT) and entecavir (ETV). LVD is the first anti-HBV nucleoside (acid) analogue used in clinical practice, and its antiviral characteristics are: strong antiviral effect, rapid onset of action, few adverse effects, but high resistance to long-term use. However, the resistance rate is high with long-term use. Meta-analysis of the efficacy of lamivudine in the treatment of HBV-associated liver failure by Zhang Yao et al. showed that the addition of lamivudine significantly reduced the morbidity and mortality rate and improved the total bilirubin and prothrombin activity levels in patients with liver failure compared with the conventional medical therapy group. Nowadays, in the era of antiviral optimization, it has become a direction of concern for clinicians whether the initial combination of LVD and ADV produces more benefits for the long-term outcome of this special population, including sustained suppression of the virus, control and stabilization of liver function, occurrence of disease complications, long-term survival and reduction of drug resistance, etc. ADV has a significant inhibitory effect on both HBV wild-type and LVD-induced viral variants Since ADV has no cross-resistance sites with other nucleosides, it is often used clinically as one of the drugs of choice for the salvage treatment of liver failure caused by resistance to other nucleosides such as LVD, ETV and LDT. However, given the low antiviral activity and slow onset of action of ADV, it is recommended to combine with other nucleoside analogues to exert their effects. ETV is the most potent anti-HBV analogue among existing nucleoside (acid) analogues, which not only has significant inhibitory effects on wild strains and mutant strains, but also remains sensitive to increased doses of drug-resistant strains of LVD. Several studies at home and abroad have shown that, on the basis of comprehensive medical treatment, the addition of ETV can rapidly and effectively inhibit viral replication in patients with HBV-related liver failure, reduce hepatocellular inflammation, halt disease progression, improve survival and reduce morbidity and mortality, and no significant adverse effects of entecavir have been found in the study, which is well tolerated by patients. ETV is one of the most powerful anti-HBV drugs, with a rapid onset of action and significant inhibition of HBV replication in the early stages, allowing patients to achieve a high HBeAg seroconversion rate. Recent studies have found that LDT can better control the virus, improve liver function, and increase the survival rate of these patients, and the incidence of adverse events is similar to that of LVD over a two-year period in patients with hepatitis B cirrhosis. LDT has not been used for the treatment of severe hepatitis B. While the efficacy of LDT in the treatment of severe hepatitis B has been initially confirmed, adverse effects such as fluctuations in liver function and elevated creatine kinase (CK) have been observed in some cases, so its long-term safety and efficacy need to be further studied. In recent years, adverse events such as renal function impairment and lactic acidosis have been reported during the clinical use of nucleoside (acid) analogs against viruses, which makes the safety of the drugs more and more important. Therefore, in view of the characteristics of HBV-related liver failure patients with rapid disease progression and high morbidity and mortality rates, the clinical antiviral treatment drugs for this special population are mostly nucleoside (acid) analogues with strong viral inhibitory effects, rapid efficacy and high safety. The effectiveness of antiviral therapy for HBV-related liver failure is also closely related to the timing of antiviral therapy. It is generally recommended that those with HBeAg(+) and HBV DNA >105copies/mL or HBeAg(I) and HBV DNA >104copies/mL should be treated with long-term antiviral therapy as early as possible. Since liver failure is often accompanied by significant viral clearance due to massive hepatocyte necrosis caused by an overly strong immune response, or low viral load due to reduced residual hepatocytes in liver fibrosis and cirrhosis, most scholars currently advocate antiviral therapy for patients with HBV DNA-positive liver failure. As long as HBV DNA is detected, even if the level of HBV DNA is low, antiviral therapy should be considered, with emphasis on rapid and potent inhibition of viral replication and prevention of drug resistance or timely management of drug resistance. Such patients should be treated with long-term antiviral therapy, and long-term effective suppression of viral replication can stabilize or even reverse the disease in some patients and save them from liver transplantation. However, it should be noted that since various complications can occur in liver failure, some patients may still die due to complications in the presence of antiviral therapy, therefore, it should be emphasized that antiviral therapy under close supervision should be accompanied by comprehensive supportive therapy and prevention of complications. For those who cannot effectively stop the progression of the disease by applying antiviral therapy, liver transplantation is required, and antiviral therapy itself can reduce the recurrence of hepatitis B after liver transplantation. In addition to the above mentioned patients with chronic severe hepatitis or decompensated cirrhosis caused by HBV requiring antiviral, European and American guidelines also suggest that: most adults with acute hepatitis B exhibit a self-limiting process and do not require routine administration of antiviral therapy; however, some patients can develop acute or subacute severe hepatitis and become life-threatening, therefore, antiviral therapy should be given to patients with a tendency to severe hepatitis and It is recommended to continue treatment for at least 3 months after the appearance of HBsAg seroconversion, or for at least 6 months if only HBeAg seroconversion without HBsAg disappearance occurs. In summary, there is sufficient evidence that early application of nucleoside (acid) analogs for HBV-associated liver failure is effective, suppressing HBV-induced liver inflammation and necrosis in the short term; indications for antiviral therapy can be extended to the acute course, viral load can be more flexible, and the duration of therapy may be indefinite (except in acute infections). However, questions such as the place of antiviral therapy for hepatitis B virus-associated liver failure in a comprehensive treatment regimen and the long-term safety of nucleoside (acid) analogs in treating this population still depend on more large-scale clinical trials in the future to better guide clinical and scientific work.