Recently, the American Association for the Study of Liver Diseases (AASLD 2024) was held in San Diego, USA. The prestigious event brought together leading experts and scholars in the field of hepatology from around the globe. The conference featured a series of captivating presentations, discussing cutting-edge liver disease treatments and the future of global liver health.At the conference, Dr. Jiajie Liao from Zhongshan Hospital, led a research team that presented a study evaluating the impact of various antiviral treatment strategies on achieving functional cure for hepatitis B. The study earned the Poster of Distinction award. As we approach the 2030 goal set by the World Health Organization (WHO) to eliminate hepatitis B, what is the current state of chronic hepatitis B (CHB) prevention and treatment in China? What lies ahead? Hepatology Digest invited Dr. Liao and Dr. Jing Chen from the School of Public Health at the Chinese University of Hong Kong to share their insights on these pressing questions.
Hepatology Digest: At this year’s AASLD conference, your team presented a study evaluating different antiviral strategies for achieving functional cure for CHB, which was recognized as a Poster of Distinction. Could you provide an overview of the current state of CHB treatment?
Dr. Jiajie Liao: According to the latest WHO data, as of 2022, 254 million people worldwide are living with chronic hepatitis B, with 1.2 million new infections and approximately 1.3 million deaths due to viral hepatitis that year alone. While significant progress has been made in infection prevention, the rising number of deaths underscores the unmet need for timely diagnosis and treatment.
With the 2030 WHO hepatitis B elimination target fast approaching, significant challenges remain:
Challenge 1: Low Diagnosis and Treatment Rates
As of 2022, only 13.4% of hepatitis B-infected individuals worldwide had been diagnosed, and just 19.5% of those diagnosed (or 2.6% of all infected individuals) were receiving treatment. In Hong Kong, these rates were 36% and 10%, respectively. Even in regions with higher diagnostic rates, treatment rates remain alarmingly low.
Challenge 2: Restricted Eligibility for Initial Treatment
The limited eligibility criteria for treatment also contribute to low treatment rates. Currently, international hepatitis B treatment guidelines recommend therapy for fewer than 30% of infected individuals. Although the updated WHO guidelines have expanded treatment eligibility to nearly 64%, this is still insufficient. Ideally, all HBV-positive patients should receive timely treatment.
Challenge 3: Delayed Diagnosis of Liver Cancer
Many patients are diagnosed with hepatocellular carcinoma (HCC) at advanced stages due to delays in treatment and monitoring. In Australia, over 82% of patients, and in South Korea, over 65%, were diagnosed outside of regular screening programs. Although early diagnosis significantly improves survival rates, the current early diagnosis rate for HCC is below 30%, with a five-year survival rate of just 14.1%. This highlights the urgent need for proactive screening and treatment to slow disease progression.
In the field of hepatitis B treatment, despite advances in antiviral therapies, achieving a functional cure—defined as sustained clearance of HBsAg, with or without seroconversion to anti-HBs—remains challenging. From a public health perspective, there’s growing debate about whether traditional diagnostic and treatment strategies for hepatitis B are truly effective. It’s clear that adhering strictly to existing guidelines will not suffice. We must significantly increase treatment rates among HBsAg-positive patients.
Hepatology Digest: Based on your study, do different antiviral strategies vary in achieving functional cure? Additionally, how do they compare in reducing the risk of liver cancer and HBV-related mortality?
Dr. Jiajie Liao: Currently, the cornerstone of CHB treatment involves nucleos(t)ide analogues (NAs), such as tenofovir and entecavir, which effectively suppress HBV replication and reduce the risk of liver disease progression, including cirrhosis and liver cancer. However, these therapies often require lifelong administration and rarely lead to HBsAg clearance.
Pegylated interferon (PegIFN), although associated with a shorter treatment duration and a higher HBsAg clearance rate than NAs, is limited in clinical use due to adverse effects and inconsistent efficacy. In recent years, combination therapy with NAs and PegIFN has garnered increasing attention. Compared to NAs monotherapy, NAs + PegIFN combination therapy has shown a 15-fold increase in HBsAg clearance rates (hazard ratio: 15.59, 95% CI: 3.22-75.49).
Overall, monotherapies with NAs or PegIFN, as well as their combination, seldom achieve functional cure. However, when achieved, the cure is usually durable, with sustained benefits even after treatment discontinuation. On the other hand, innovative therapies may demonstrate higher functional cure rates at the end of treatment (typically 24 weeks). Unfortunately, these therapies often face significant HBsAg rebound after discontinuation, diminishing their long-term impact.
Our study evaluated the efficacy and cost of combination therapy (NAs + IFN) and innovative therapies (New therapies + IFN) compared to long-term NAs monotherapy [2]. Using a Markov model, we simulated the natural progression of CHB and assessed different strategies in HBV-endemic regions like the Asia-Pacific. The model incorporated data from the latest literature and prior regional studies, covering parameters for disease progression and treatment costs at various stages.
Key findings include:
- Combination therapy (NAs + IFN) significantly reduced HCC incidence by over one-third and HBV-related mortality by nearly 25% over 30 years, compared to standard long-term NAs monotherapy.
- Innovative therapies, while promising in achieving functional cure, had a minimal long-term impact on HCC incidence and HBV-related mortality, with reductions of just 1.2% and 0.7%, respectively.
These results emphasize the importance of balancing short-term cure rates with long-term disease burden reduction when considering antiviral strategies. Future CHB treatment approaches should not solely focus on novel therapies but also explore the potential of existing treatments, such as combination therapy, to enhance efficacy and improve disease control.
Hepatology Digest: Your study also evaluated the incremental cost-effectiveness ratio (ICER) of various strategies. Could you explain this concept and, based on your findings, which strategy offers the best cost-effectiveness in the Asia-Pacific region?
Dr. Jiajie Liao: The incremental cost-effectiveness ratio (ICER) is a critical metric in health economics, used to assess the cost-effectiveness of different strategies. It represents the additional cost required to achieve an additional unit of health benefit, typically measured in quality-adjusted life years (QALYs).
Simply put, ICER compares the costs and outcomes of two strategies. The formula divides the cost difference by the effect difference (in QALYs) and compares this ratio to a willingness-to-pay (WTP) threshold, often defined by the per capita GDP. According to WHO guidelines:
- ICERs below one GDP per capita indicate high cost-effectiveness.
- ICERs below three times GDP per capita are considered cost-effective.
- Strategies exceeding this threshold are generally deemed not cost-effective.
Our research compared the ICER of various CHB treatment strategies in the Asia-Pacific. The findings revealed that combination therapy (NAs + IFN) offered the best cost-effectiveness. It improved health outcomes in terms of life years and QALYs while demonstrating ICERs below the GDP per capita across Asia-Pacific countries, indicating efficient use of healthcare resources.
In contrast, while innovative therapies showed potential for functional cure, they were not cost-effective in low- and middle-income countries, being viable only in high-income regions. This highlights the balance achieved by combination therapy between cost and effectiveness, making it a more practical choice for the Asia-Pacific.
In summary, combination therapy (NAs + IFN) currently stands out as the most cost-effective strategy for CHB treatment in the region, offering an optimal balance between health benefits and costs. We are now conducting further economic evaluations comparing combination therapy to treatment cessation strategies, aiming to provide stronger evidence for the most cost-effective approach to CHB management.
