From the Guidelines
Patients with hepatitis B e antigen (HBeAg) negative and hepatitis B e antibody (anti-HBe) positive should be treated with antiviral medications if they have high viral loads (typically >2000 IU/mL) and elevated liver enzymes or evidence of significant liver fibrosis. This serological profile suggests that the virus has undergone a mutation in the precore or core promoter region, resulting in reduced or absent HBeAg production despite ongoing viral replication, a phase often called HBeAg-negative chronic hepatitis B 1. Key factors to consider in treatment decisions include:
- HBV DNA levels
- ALT levels
- Evidence of liver damage Recommended antiviral medications for these patients include entecavir (0.5mg daily), tenofovir disoproxil fumarate (300mg daily), or tenofovir alafenamide (25mg daily) 1. These medications are typically long-term or indefinite treatments as they suppress viral replication but rarely eliminate the virus completely. Regular monitoring of liver function, viral load, and periodic assessment for complications like hepatocellular carcinoma is essential for these patients 1. It is also important to distinguish between true inactive HBV carriers and patients with active HBeAg-negative CHB, as the former have a good prognosis with a very low risk of complications, while the latter have active liver disease with a high risk of progression to advanced hepatic fibrosis, cirrhosis, and subsequent complications such as decompensated cirrhosis and HCC 1.
From the Research
Hepatitis B e Antigen Negative and Hepatitis B e Antibody Positive
- Hepatitis B e antigen (HBeAg) negative and hepatitis B e antibody (anti-HBe) positive patients are those who have developed antibodies against the HBeAg, indicating a response to treatment or a natural immune response 2, 3.
- The presence of anti-HBe antibodies is often associated with a lower viral load and a reduced risk of liver damage 4, 5.
- Studies have shown that patients with HBeAg negative and anti-HBe positive status can still have detectable hepatitis B virus (HBV) DNA and HBV RNA, indicating ongoing viral replication 3, 5.
Treatment and Outcomes
- Nucleos(t)ide analogues (NAs) are effective in suppressing HBV DNA and inducing HBeAg seroconversion in patients with chronic hepatitis B (CHB) 2, 4.
- The combination of entecavir and tenofovir has been shown to be effective in achieving virologic suppression in patients with previous NA treatment failure 4.
- Long-term treatment with NAs can lead to a significant decline in liver stiffness values and a reduced risk of hepatic decompensation 5.
- However, the development of drug resistance and the risk of hepatocellular carcinoma (HCC) remain concerns in patients with CHB, even those with HBeAg negative and anti-HBe positive status 4, 5.
Biomarkers and Predictors
- HBV RNA and hepatitis B core-related antigen (HBcrAg) have been identified as potential biomarkers for predicting outcomes in HBeAg negative patients with CHB 3.
- The measurement of these biomarkers can help identify patients who are at risk of severe alanine transaminase flares and HBV DNA reactivation after treatment withdrawal 3.
- Quantitative HBV surface antigen (qHBsAg) levels have also been shown to be a predictor of treatment outcomes and potential candidates for treatment discontinuation 5.