Management of immune-tolerant chronic hepatitis B

The immune-tolerant (IT) phase of chronic hepatitis B is a distinct stage of infection, characterized by high HBV replication, normal ALT levels, and minimal liver inflammation. Despite its classification as a benign phase, growing evidence challenges this notion, revealing immune activation, HBV DNA integration, and potential oncogenic processes even in the absence of elevated ALT. The IT phase’s prolonged high viral replication raises concerns about its implications for HCC risk. Histological studies show that significant inflammation and fibrosis may exist in patients meeting IT criteria, suggesting that the current definitions may underestimate disease activity. Treatment during the IT phase remains controversial, with international guidelines largely recommending against antiviral therapy due to its limited efficacy and potential risks. However, subsets of IT patients may benefit from early intervention. The risks and benefits of therapy in IT chronic hepatitis B are not fully understood, and the lack of consensus regarding treatment thresholds further complicates clinical decision-making. This review highlights the importance of redefining IT chronic hepatitis B to include virological and histological parameters and calls for long-term studies to clarify the role of therapy in reducing fibrosis progression and HCC risk. A more precise understanding of the IT phase is essential to balance the risks of treatment against its potential benefits and to inform future therapeutic strategies.