Editor's Note: Antiviral therapy plays a crucial role in reducing the risk of liver cancer and delaying disease progression in patients with chronic hepatitis B (CHB). The survival rate and quality of life for CHB patients have been steadily improving. However, the treatment needs of "Small Three Yang" (HBsAg, anti-HBe, and anti-HBc positive) patients have often been overlooked. At the 17th National Clinical Conference on Liver Diseases held on May 25, 2024, Hepatology Digest interviewed the conference chairman, Professor Xiaoguang Dou from Shengjing Hospital of China Medical University, to discuss clinical cure strategies for "Small Three Yang" patients. Here is a summary of the interview for our readers.Hepatology Digest: As the chairman of this year’s National Clinical Conference on Liver Diseases, could you introduce the key topics and highlights of the conference?
Professor Xiaoguang Dou: This year marks the 17th consecutive National Clinical Conference on Liver Diseases. This influential conference was initially organized by Professor Ren Hong from the Second Hospital of Chongqing Medical University and the Chinese Journal of Hepatology. Eight years ago, the conference began to be jointly hosted by the Chinese Journal of Hepatology, Journal of Clinical Hepatology, and Hepatology Journal. This year’s conference is primarily planned by Professor Chengwei Chen’s team from the 905 Hospital of People’s Liberation Army Navy.
The National Clinical Conference on Liver Diseases attracts numerous experts in the liver disease field each year for several reasons.
First, the conference topics are highly targeted, focusing on clinical hotspots and challenges. Second, liver diseases encompass not only viral hepatitis but also autoimmune hepatitis, drug-induced liver injury, genetic metabolic liver diseases, and more. In addition to new clinical diagnostic advancements, there have been many new research developments from basic science to clinical practice. Third, this year’s conference invited over 60 renowned experts from both China and abroad to present on clinical issues. The conference also includes discussion sessions where other participants can pose questions or offer different perspectives on the experts’ presentations. Notably, we have invited Academician Zhuang Hui from Peking University Health Science Center to participate in the discussions.
These factors make the National Clinical Conference on Liver Diseases highly engaging for both basic research and clinical experts. I believe all participants will benefit greatly.
Hepatology Digest: Recently, your team discovered that pegylated interferon (Peg-IFN) has a high clinical cure rate for HBeAg-negative CHB patients with normal alanine aminotransferase (ALT). What significance does this research hold for CHB treatment?
Professor Xiaoguang Dou: Since the hepatitis B vaccine was included in the national immunization program, new CHB cases in China have become rare. However, with a population of 1.4 billion, there are still approximately 75 million existing CHB cases. Over time, the immune response in these individuals may clear the virus but not completely, resulting in HBeAg-negative CHB, commonly referred to as “Small Three Yang.”
“Small Three Yang” patients are often overlooked because they have low viral loads and mostly normal ALT levels, yet they face a high risk of disease progression. Antiviral therapy for CHB includes two types of medications: nucleos(t)ide analogues (NAs) and pegylated interferon.
Pegylated interferon treatment can achieve higher clinical cure rates, characterized by sustained undetectable HBV, HBeAg negativity, and non-progressive liver disease. In recent years, we have focused on these patients, typically older and HBeAg-negative. Regardless of their ALT levels, we treated them with interferon to observe if they could achieve higher clinical cure rates.
Initially, our team conducted a single-center retrospective study, which showed excellent treatment outcomes irrespective of ALT levels. Consequently, we initiated a nationwide multicenter clinical study involving HBeAg-negative, HBsAg-positive, ALT-normal CHB patients to observe clinical cure rates and contribute to the “Treat All” strategy for CHB.
The study results indicated an average clinical cure rate (HBsAg clearance) of 35% among these patients, with rates exceeding 50% for those with low baseline viral loads and HBsAg levels below 1500 IU/mL. In comparison, nucleos(t)ide analogues showed high baseline virus undetectable rates (over 90%) but low HBsAg clearance rates. Therefore, interferon is the preferred treatment for these patients.
Moreover, without antiviral treatment, “Small Three Yang” patients have high incidences of cirrhosis and liver cancer. Reducing HBV-related liver cancer is our ultimate goal, and this is one reason we prefer interferon treatment.
In the future, we hope clinical experts nationwide will adopt interferon therapy for “Small Three Yang” patients to improve clinical cure rates. We plan to include interferon treatment recommendations for this patient group in the next guideline revision.
