Breakthroughs Have Been Made in Functional Cure of Hepatitis B

Source: Life Times

Interviewed Experts: Chen Yu, Chief Physician, the Fourth Department of Hepatology Center, Beijing YouAn Hospital Affiliated to Capital Medical University; Dong Jinling, Chief Physician

Reporter of This Newspaper: Zhang Bingyu

There are approximately 75 million patients with chronic hepatitis B (hereinafter referred to as hepatitis B) in China, accounting for about 1/3 of the global total. If treatment is not timely or the disease is poorly controlled, the hepatitis B virus will continuously damage liver cells. Some patients will progress to liver cirrhosis or liver cancer, and a few will even develop liver failure, which seriously threatens the life and health of patients. For a long time, the treatment of hepatitis B has faced the dilemmas of lifelong medication and low cure rate. Recently, breakthroughs in the research and development of new drugs have brought new dawn for the functional cure of hepatitis B.

Dong Jinling, Chief Physician of the Fourth Department of Hepatology Center, Beijing YouAn Hospital Affiliated to Capital Medical University, introduced that at present, the conventional treatment regimens for hepatitis B include long-term oral nucleos(t)ide analogs (NAs) antiviral drugs, monotherapy with long-acting interferon or short-acting interferon, or the combination of interferon and NAs. However, all these regimens have certain limitations. First, the course of treatment is generally very long. Oral NAs mainly inhibit the replication of hepatitis B virus, but cannot completely eliminate the virus. It is difficult for patients to achieve sustained immunological control, with a high recurrence rate after drug withdrawal, so long-term medication is required. Interferon-based treatment regimens require specialists to balance efficacy and side effects under guidance, and the treatment course for patients pursuing functional cure is mostly 48 to 96 weeks. Second, the clearance rate of hepatitis B surface antigen is limited. The hepatitis B surface antigen seroconversion rate of patients using NAs alone is less than 3%, and even if the NAs combined with interferon regimen is adopted, the clearance rate can only be increased to about 30% in specific populations.

At present, "functional cure of hepatitis B" is regarded as the ideal therapeutic target in clinical practice. It refers to that 24 weeks after stopping antiviral treatment, the patient's serum hepatitis B surface antigen continues to show negative conversion (less than 0.05 IU/mL) and hepatitis B virus DNA is lower than the lower limit of quantification (10 IU/mL), with or without the emergence of hepatitis B surface antibody; at the same time, it is necessary to meet the requirements of continuous negative conversion of serum hepatitis B e-antigen, alanine aminotransferase returning to normal, finally obtaining the improvement of liver histology and reducing the risk of hepatocellular carcinoma. However, covalently closed circular DNA and integrated hepatitis B virus DNA can still remain in the liver.

It is extremely difficult to achieve functional cure of hepatitis B. Chen Yu, Chief Physician of the Fourth Department of Hepatology Center, Beijing YouAn Hospital Affiliated to Capital Medical University, explained that the existing treatments cannot eliminate the covalently closed circular DNA and integrated hepatitis B virus DNA of hepatitis B virus in liver cells, which is the root cause of virus recurrence; drugs are difficult to reverse the related T cell exhaustion, so the immune system cannot effectively monitor the virus; even if functional cure is achieved, some patients may still face virus reactivation and recurrence risks due to changes in their own immune function (such as immunosuppression).

Nevertheless, breakthrough progress has been made in the research and development of new-target drugs. Among many new drugs, the first one to enter phase 3 clinical trials is the antisense oligonucleotide (ASO) Bepirovirsen (GSK836). Not long ago, this drug achieved positive results in two phase 3 clinical trials, and it is planned to apply for marketing in the first quarter of 2026, which is expected to become one of the first new drugs to promote the functional cure of hepatitis B. Chen Yu said that this drug exerts anti-hepatitis B virus effects mainly through three mechanisms: first, it specifically degrades hepatitis B virus RNA to reduce the expression of viral proteins; second, it reduces the overall viral DNA level and inhibits virus replication; third, it stimulates the immune system to restore the specific immune function against hepatitis B virus. In general, this drug has obvious advantages in promoting the functional cure of hepatitis B.

‌Shorter treatment course‌: It breaks the dilemma of "lifelong medication" in traditional NAs treatment. After patients treated with NAs receive Bepirovirsen for 24 weeks and then stop the drug, followed by 24 weeks of consolidation treatment with NAs, some of them can achieve functional cure.

‌Wide applicable population‌: The baseline hepatitis B surface antigen level of patients included in its phase 3 clinical study ranges from 100 to 3000 IU/mL. The 2025 Expert Consensus on Clinical Practice for Functional (Clinical) Cure of Chronic Hepatitis B in China mentions that the population who are easy to achieve functional cure have a hepatitis B surface antigen level below 500 IU/mL, and the "Chinese Chronic Hepatitis B Clinical Cure (Everest) Project" recommends that the advantageous population have a level below 1500 IU/mL. In contrast, this drug expands the range of surface antigen titer applicable to hepatitis B patients.

‌Good safety‌: Data shows that most of the adverse reactions of this drug are concentrated at the injection site, with a low incidence of severe adverse reactions and higher patient tolerance.

Dong Jinling said that if this drug is successfully launched on the market, it will lead the diagnosis and treatment of hepatitis B into a new stage of functional cure, bringing far-reaching multi-dimensional impacts. For patients, it is expected to help more patients get rid of the "hepatitis B" label, not only achieving negative conversion of hepatitis B surface antigen and reducing the risk of liver cirrhosis and liver cancer, but also relieving psychological pressure and improving the quality of life in aspects such as employment and social interaction. For clinicians, with this new therapeutic weapon, the functional cure rate of hepatitis B can be significantly improved, providing more accurate treatment options for patients with different baseline levels, and helping to achieve the global public health goal of "eliminating hepatitis B by 2030".

Disclaimer: The information in this article is for popular science reference only and does not constitute medical diagnosis advice.