From the Guidelines
Antiviral treatment is generally not recommended for patients with hepatitis B in the immune tolerant phase, as the risk of liver disease progression is low and treatment may not provide significant benefits, according to the most recent guidelines 1.
Key Characteristics of Immune Tolerant Phase
- High levels of HBV DNA (typically ≥10^7 IU/mL)
- Normal alanine aminotransferase (ALT) levels
- Minimal liver inflammation
- Little to no liver fibrosis
Monitoring and Treatment Considerations
- Regular monitoring every 3-6 months with liver function tests and HBV DNA levels to detect transition to the immune active phase
- Periodic assessment for hepatocellular carcinoma in appropriate patients
- Treatment may be considered if there is evidence of significant fibrosis or family history of hepatocellular carcinoma, despite being in the immune tolerant phase
Recent Studies and Guidelines
- A 2022 study published in Clinical and Molecular Hepatology suggests that the immune tolerant phase is characterized by a low risk of liver disease progression, and treatment may not be necessary 1
- A 2025 study published in Liver International highlights the potential oncogenic implications of clonal expansion in the immune tolerant phase, but does not provide conclusive evidence for treatment in this phase 1
- The guidelines from the Korean Association for the Study of the Liver (KASL) recommend monitoring rather than treatment for patients in the immune tolerant phase, unless there are signs of significant fibrosis or inflammation 1
From the Research
Hepatitis B Immune Tolerant Phase Treatment
- The hepatitis B immune tolerant phase is characterized by HBeAg positivity, high levels of HBV DNA, and normal alanine aminotransferase levels 2.
- According to international guidelines, patients in this phase are typically recommended for observation without antiviral treatment due to the low risk of disease progression and the lack of effective antiviral agents 2, 3.
- However, some studies suggest that progression to hepatic fibrosis and hepatocellular carcinoma may occur in patients who are in the immune tolerance phase, highlighting the need for close monitoring 2, 3.
Patient Evaluation and Treatment Consideration
- The decision to treat patients in the immune tolerant phase should be individualized based on factors such as age, liver fibrosis status, and family history of liver cancer 4, 3.
- Patients over 40 years old or those with advanced liver fibrosis may require treatment, while those under 30 years old can be monitored for ALT and HBV DNA levels 3.
- Certain subgroups of immunotolerant patients, such as those receiving immunosuppressive treatment or chemotherapy, pregnant women with high HBV DNA levels, and healthcare professionals with high viraemia levels, may also require treatment 3.
Treatment Response and Outcomes
- Studies have shown that immune-tolerant patients have a lower HBeAg seroconversion rate when receiving antiviral therapy, such as pegylated interferon or nucleos(t)ide analogue treatment 5.
- The latest clinical trial using tenofovir disoproxil fumarate-based therapy also reported low HBeAg seroconversion rates (<5% at 4 years of treatment) in immune-tolerant patients 5.
- Therefore, current antiviral therapy is not recommended for immune-tolerant patients unless they have advanced liver fibrosis, and novel agents targeting the HBV template are needed to improve treatment outcomes 5.