Editor’s Note:At the 2025 World Hepatitis Day Campaign Conference and the 7th Academic Conference on Clinical Cure of Chronic Hepatitis B, hosted by the China Foundation for Hepatitis Prevention and Control, Professor George Lau, Chairman of Hong Kong’s Humanity Medical Group and Chief Physician at Zhongshan Hospital affiliated with Fudan University, shared insights on the most cost-effective strategies for HBV antiviral therapy from an economic perspective. Hepatology Digest invited Prof. George Lau for an in-depth interview on the current status of hepatitis B prevention and treatment as well as economic evaluation. 

Hepatology Digest: As we approach the WHO’s 2030 goal to eliminate hepatitis B, what is the current state of chronic hepatitis B prevention and treatment in China? Could you also discuss the main challenges from an economic standpoint?

Prof. Lau: In terms of hepatitis B surface antigen (HBsAg) positivity rates, China has made remarkable progress in hepatitis B control. Thanks to widespread vaccination, the HBsAg positivity rate in China has dropped to 5%–6%, compared with around 15% when I first arrived in China. However, liver cancer related to hepatitis B remains a serious problem. We had hoped to reduce liver cancer incidence by more than 35% by 2030, but the reality is that, as of 2025, liver cancer incidence has not decreased — in fact, it is rising.

China sees about 380,000 new cases of hepatitis B–related liver cancer annually. Notably, member countries of the Asian-Pacific Association for the Study of the Liver (APASL) account for 70% of global liver cancer cases. This raises an important question: Why, despite having advanced diagnostic tools, effective vaccines, and antiviral therapies, is liver cancer incidence still increasing? The key issue lies in how to better apply these technologies in population-level prevention. As Chair of the APASL Guidelines Group for Hepatitis B, I am working with over 40 experts from 28 member countries to explore ways to optimize clinical use of existing technologies so as to effectively lower liver cancer incidence. Early screening and treatment options for liver cancer are continuously improving; theoretically, incidence should be declining rather than rising.

Hepatology Digest:Your team conducted research comparing different antiviral strategies in achieving functional cure. Are there differences among these strategies in terms of functional cure rates? What advantages do they offer in reducing liver cancer and HBV-related mortality?

Prof. Lau: Functional cure means HBsAg seroclearance. Studies over the past two to three decades have confirmed that HBsAg clearance significantly reduces liver cancer risk. Emerging small-molecule drugs such as antisense oligonucleotides (ASOs) can lower HBsAg levels or achieve seroclearance, but overall success rates remain low and they are mainly suitable for patients whose HBsAg levels are already low. These patients tend to be older, so the benefit of HBsAg clearance is relatively limited because HBsAg levels naturally decline with age.

In internal discussions within APASL, we proposed three recommendations: First, newly developed functional cure drugs should achieve an HBsAg clearance rate of at least 30%. Second, the optimal target population should be patients under 40 years old; those aged 60–70 gain limited benefit. Third, considering the accessibility of nucleos(t)ide analogues in public health settings (domestically produced drugs cost about 100 RMB per year, imported ones several thousand RMB), the annual cost of new drugs should not exceed 3,000–4,000 RMB to be widely adoptable. Based on these criteria, we aim to deepen our understanding of immune mechanisms and small-molecule drug properties to optimize existing treatment regimens, helping more HBV carriers achieve early HBsAg clearance and thereby reduce liver cancer risk.

Hepatology Digest:Your study also examined the incremental cost-effectiveness ratios (ICERs) of various treatment strategies. In your view, which strategy offers the best ICER in the Asia-Pacific region, particularly in China?

Prof. Lau: Currently, the most cost-effective strategy is combination therapy using long-acting interferon plus nucleos(t)ide analogues. Long-acting interferon has been used for 20 years, and a 48-week course yields an HBsAg clearance rate of 3%–7%, with long-term follow-up up to 15 years. Professor Wen-hong Zhang’s “Oasis project” on chronic hepatitis B also demonstrated that patients treated with interferon have a significantly lower incidence of liver cancer than untreated patients. For patients who cannot tolerate interferon or fail to achieve HBsAg clearance — especially those who are HBeAg-positive with e-antigen loss or HBeAg-negative but abnormal liver function and detectable HBV DNA — nucleos(t)ide analogues remain necessary.

For patients on long-term nucleos(t)ide analogue therapy with HBsAg levels below 3,000 IU/mL, adding long-acting interferon can raise the HBsAg clearance rate to 25%–30%. From a practical standpoint, the combination of long-acting interferon and nucleos(t)ide analogues is both clinically effective and reasonably priced, affordable for most patients and reimbursable by insurance. It is worth noting that domestic technological platforms have improved dramatically; we can now easily perform quantitative HBsAg testing — something even difficult to access in places like Hong Kong — providing an important basis for individualized treatment planning. By monitoring quantitative HBsAg (not just HBV DNA), we can better tailor each patient’s regimen and add interferon at the right time, ultimately enabling safe discontinuation of therapy. With these strategies, we believe we can significantly reduce liver cancer incidence and mortality.