Editor's Note: According to the World Health Organization, there are currently about 257 million chronic hepatitis B (CHB) patients worldwide, with approximately 70 million HBV (hepatitis B virus) carriers in China, making it one of the countries with a high prevalence of chronic HBV infection. Due to factors such as viral characteristics, immune status, and environmental influences, domestic and international guidelines typically classify the natural history of chronic HBV infection into four phases: immune tolerance, immune active, immune control, and reactivation. Identifying these phases is crucial for predicting patient prognosis and guiding intervention strategies. However, recent studies have shown that a considerable number of chronic HBV infection patients cannot be categorized into any of these four phases based on existing guidelines or natural history criteria, leaving them in an indeterminate phase or gray zone, which is not covered by international and domestic clinical guidelines. Recently, at the 17th National Clinical Conference on Liver Diseases in 2024, Professor Peng Hu presented a report titled "Related Research on Indeterminate Phase of Chronic Hepatitis B." Hepatology Digest conducted an interview with Professor Peng Hu regarding CHB's indeterminate phase. Here is the summarized interview for our readers.Hepatology Digest: Could you please define the indeterminate phase of CHB? Is there a standardized definition currently? Where does it stand in the natural course of HBV infection, and what is its prevalence among chronic HBV-infected individuals?
Professor Peng Hu: The definition of the indeterminate phase is currently quite clear. The indeterminate phase of CHB is primarily defined based on the natural history of hepatitis B, which itself is based on HBV viral load and ALT levels. However, in clinical practice, we find that some patients do not strictly adhere to classifications based on HBV viral load and ALT levels, placing them in the indeterminate phase. Currently, the indeterminate phase accounts for 30% to 50% of all CHB patients.
Hepatology Digest: What changes typically occur in liver function, viral replication status, and immune status in patients with the indeterminate phase of CHB?
Professor Peng Hu: In patients in the indeterminate phase, liver biopsies of those traditionally considered to be in the immune tolerant or immune control phases show that over 50% have clear inflammation or fibrosis, indicating that they are actually in a defined phase and should receive active antiviral treatment.
Hepatology Digest: What treatment strategy do you recommend for patients in the indeterminate phase of CHB, and why?
Professor Peng Hu: In fact, our consensus and guidelines in China are already at the forefront globally. After the modification of the indeterminate phase standard, the proportion of indeterminate phase patients in China has decreased, allowing more suitable patients to receive treatment. According to international guidelines, the risk of liver fibrosis, cirrhosis, and liver cancer in indeterminate phase patients will increase yearly if left untreated. Therefore, active antiviral treatment is recommended for these patients. Recent studies have shown that for clearly defined indeterminate phase patients, antiviral treatment can reduce their risk of developing liver cancer by over 75% in the next 10 to 15 years, which is a significant benefit for patients. Conversely, if we neglect treatment for this patient group, their risk of liver fibrosis, cirrhosis, and liver cancer will increase dramatically. Therefore, timely and standard antiviral treatment for indeterminate phase patients can provide long-term benefits.
