Department of Gastroenterology, Faculty of Medicine, University of Yamanashi
Background: The dynamics and the clinical significance of serum HBV-RNA levels and their sequences during the emergence of antiviral resistance are yet to be elucidated.Methods: Using sera of HBV patients receiving NA therapy experiencing viral breakthrough, simultaneous deep sequencing of HBV-RNA /HBV-DNA was conducted (n = 4). The dynamics of serum HBV-RNA levels were investigated in patients experiencing had viral breakthrough (n = 7). Results: In patients experiencing viral breakthrough, no NA resistance mutation was detected in serum HBV-RNA immediately before the breakthrough. However, NA-resistant sequences appeared at the rates of 0%, 3%, 14%, and 100%, and the NA-resistant HBV-RNA sequence rate was correlated with the peak HBV-DNA titer multiplied by the HBV-DNA detection duration during the breakthrough (R2 = 0.978) observed before re-disappearance of HBV-DNA following the addition of new NA. In the analysis of serum HBV-RNA dynamics, HBV-RNAs of four patients without viral breakthrough all became undetectable after two years of therapy (4/4, 100%) while HBV-RNAs became undetectable in only one among seven patients in those with viral breakthrough (1/7, 14%, p < 0.05). Conclusion: The dynamic analysis of HBV-RNA sequence and serum HBV-RNA level is considered to be useful for understanding as well as for predicting the emergence of resistance.