Unresolved issues of immune tolerance in chronic hepatitis B

During the natural course of chronic hepatitis B virus infection, immune-tolerant phase is characterized by high viral replication, the presence of HBV e antigen (HBeAg), and normal or minimally elevated serum alanine aminotransferase. Immune-tolerant phase is usually regarded as a benign course of the disease. International guidelines recommend observation rather than treatment during immune-tolerant phase. In this article, we review unresolved issues related to the definition of true immune-tolerant phase and the benefit of antiviral treatment. Defining true immune-tolerant phase requires a careful approach and long-term follow-up. In previous studies, many patients were misclassified as being immune-tolerant phase. Noninvasive methods of assessing fibrosis are warranted for patients in the immune-tolerant phase. Yet, there has been controversy over the benefit and harm of antiviral treatment for immune-tolerant phase patients. Thus, further larger scale studies are needed to investigate the prognosis of patients in true immune-tolerant phase and their need for antiviral therapy.