With significant progress in hepatitis B treatment, particularly in the pursuit of a functional cure, the quantification of hepatitis B surface antigen (HBsAg) has emerged as a critical factor in treatment planning. At the 2024 Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Hepatology Digest interviewed Dr. Grace Lai-Hung Wong from The Chinese University of Hong Kong. She provided in-depth insights into the relationship between HBsAg levels, the natural course of hepatitis B, and prognosis, and discussed the latest advancements in the application of HBsAg quantification in hepatitis B management.Understanding the Significance of Quantitative HBsAg
Hepatology Digest: In your presentation, you discussed the quantification of HBsAg. How does it contribute to understanding HBV infection and disease progression?
Dr. Grace Lai-Hung Wong: HBsAg levels are closely tied to the natural history and prognosis of hepatitis B. Regarding the natural history, the significance of HBsAg levels differs in HBeAg-positive and HBeAg-negative patients.
For HBeAg-positive patients, higher HBsAg levels are often desirable as they typically indicate an active immune clearance phase, a relatively stable condition, normal ALT levels, and minimal liver fibrosis. Conversely, low HBsAg levels in HBeAg-positive patients may suggest immune-related symptoms and more severe fibrosis.
In HBeAg-negative patients, lower HBsAg levels are preferable, as they generally reflect better immune control and reduced HBV activity.
From a prognostic perspective, studies have shown that when HBsAg levels drop to a specific threshold, discontinuation of oral antiviral therapy becomes feasible with a lower risk of relapse. For instance, in Asian populations, HBsAg levels below 100 IU/mL are associated with approximately 90% non-relapse rates after treatment cessation. However, some experts are cautious, noting that while 90% avoid relapse, the remaining 10% may experience significant disease activity. As such, many believe that lowering HBsAg to thresholds like 50 IU/mL or even 10 IU/mL provides greater safety when stopping treatment.
Advancements in HBsAg Quantification for Personalized Hepatitis B Management
Hepatology Digest: What recent advancements have emerged in the application of HBsAg quantification for managing hepatitis B? How does it help tailor treatment plans?
Dr. Grace Lai-Hung Wong: The field of hepatitis B treatment has seen remarkable progress, particularly in the pursuit of a functional cure. Phase I, II, and III clinical trials are underway, focusing on tailoring treatment strategies to individual patients. A key finding from these studies is that HBsAg levels play a pivotal role in treatment selection.
Current treatment protocols often set an HBsAg threshold as a criterion for inclusion in specific treatment regimens. These thresholds vary depending on the study or treatment plan, ranging from 3000 IU/mL to as low as 500 IU/mL or even 200 IU/mL. By evaluating HBsAg levels, clinicians can better match patients to the most appropriate therapeutic strategies.
HBsAg levels also offer insights into the stage of disease progression. For patients with high HBsAg levels, combination therapies may be necessary to clear HBsAg effectively. In contrast, patients with low HBsAg levels often demonstrate better immune control and may require fewer interventions to achieve successful clearance.
HBsAg Decline and Treatment Response
Hepatology Digest: Research suggests that changes in HBsAg levels may correlate with treatment responses. Could you elaborate on this and share any recent findings?
Dr. Grace Lai-Hung Wong: Patients with low baseline HBsAg levels and rapid declines during the first three to six months of treatment generally have higher chances of treatment success.
However, treatment responses vary between therapies. For example, with small interfering RNA (siRNA) therapies, many patients experience dramatic reductions in HBsAg—sometimes to 1/100 or even 1/1000 of their baseline levels—within the first two to three months. While these reductions are encouraging, maintaining these lowered levels and preventing rebounds require additional measures.
Key factors include the patient’s immune system. If their immune response is strong enough to control the virus, HBsAg levels are more likely to remain stable. Furthermore, treatment regimens incorporating agents that enhance immune clearance improve the likelihood of sustained low HBsAg levels after treatment ends. These approaches collectively increase the chances of a durable response.
Reflections and Highlights from AASLD 2024
Hepatology Digest: What are your reflections on this year’s AASLD meeting? Could you share any notable research highlights?
Dr. Grace Lai-Hung Wong: This year’s meeting featured numerous impactful presentations on hepatitis B, emphasizing significant strides in cure strategies. While siRNA monotherapy has demonstrated rapid reductions in HBsAg levels, maintaining these reductions remains a challenge. Successful cases often rely on combination therapy.
Immune-based therapies are becoming increasingly diverse. Some approaches use specific antibodies to directly lower HBsAg levels, while others stimulate the patient’s immune system, such as therapeutic vaccines or agents that activate immune control. These methods are instrumental in maintaining stable, low HBsAg levels.
In summary, a clear message from this year’s conference is that functional cure strategies for hepatitis B will depend on combination therapies. However, the optimal combinations, timing, and duration of these treatments require further investigation and data analysis.
