Virological Markers Enhance Prediction of Hepatitis B Treatment Outcomes

A recent systematic review has identified specific virological markers as significant predictors for treatment outcomes in individuals with chronic hepatitis B receiving pegylated interferon (PEG-IFN) therapy. The study aimed to enhance the prediction of functional cure, defined as hepatitis B surface antigen (HBsAg) loss, and hepatitis B e antigen (HBeAg) loss, addressing the critical need for improved predictive tools in a condition where current cure rates remain notably low.

Methodology

Researchers conducted a comprehensive systematic review and meta-analysis of 38 studies, encompassing a substantial cohort of 6,179 patients. Data was meticulously gathered from leading scientific databases including PubMed, Embase, the Cochrane Library, and Web of Science, with searches extended up to November 2023. The predictive efficacy of various virological markers was rigorously assessed using the summary receiver operating characteristic curve (AUROC) to determine their discriminative ability.

Key Findings

The analysis revealed distinct markers demonstrating strong predictive capabilities for different treatment outcomes:

For predicting functional cure, specific HBsAg markers stood out:

• HBsAg decline at week 24: This marker exhibited the highest discriminative ability (AUROC 0.89) and impressive sensitivity (0.88) for forecasting functional cure.
• Baseline HBsAg levels: These levels showed comparable discriminative ability (AUROC 0.86) and the highest specificity (0.79) among the markers assessed.

Both HBsAg decline at week 24 and baseline HBsAg levels were found to be significantly more effective predictors than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (P < 0.001 for all comparisons).

For the prediction of HBeAg loss or seroconversion, several markers demonstrated comparable predictive values, with AUROC ranging from 0.75 to 0.78. These included:

• HBV RNA levels
• HBV DNA levels
• HBeAg levels
• HBeAg decline at week 12
• HBV DNA decline at week 24
• HBeAg decline at week 24

Specifically, HBV RNA and HBeAg levels at week 24 provided optimal sensitivity (0.87). Meanwhile, HBeAg decline at week 12 showed the highest specificity (0.83) in this category.

Conclusion

The systematic review concluded that HBsAg decline at week 24 and baseline HBsAg levels are superior indicators for predicting functional cure in chronic hepatitis B patients undergoing PEG-IFN treatment. For the prediction of HBeAg loss, on-treatment HBV RNA and HBeAg levels, along with their dynamic changes, were identified as reliable predictive indicators. These findings offer valuable insights for improving treatment strategies and patient management.