Chronic hepatitis B is a progressive disease caused by the hepatitis B virus (HBV). Without effective antiviral therapy, the disease can eventually lead to liver cirrhosis, liver failure, or hepatocellular carcinoma (HCC), posing a serious threat to life. For patients undergoing antiviral therapy, timely and accurate evaluation of treatment efficacy and drug discontinuation monitoring are crucial for optimizing clinical strategies and improving patient management.
The persistent existence of covalently closed circular DNA (cccDNA) is the primary reason for the chronic nature of HBV infection, the difficulty in curing chronic hepatitis B (CHB), and the high relapse rate after treatment cessation. Previous studies have shown that serum HBV DNA and HBsAg levels correlate positively with the activity of intrahepatic cccDNA, and they are widely used as indicators to assess virological response, monitor treatment efficacy, and guide drug discontinuation. However, the disappearance of serum HBV DNA does not necessarily indicate that cccDNA in liver tissue has been eliminated or is transcriptionally silent.
Serum HBV RNA accurately reflects cccDNA transcriptional activity, playing an important role in assessing cccDNA presence and antiviral drug efficacy.
HBV RNA testing can be used to evaluate the efficacy of nucleos(t)ide analogues (NAs) in antiviral therapy. Compared to serum HBV DNA, HBsAg, and ALT, the decline in HBV RNA levels is considered the most reliable serological marker for predicting HBeAg seroconversion. HBV RNA detection is thus highly effective for assessing treatment outcomes and contributes to both drug development and disease management.
In addition to NA therapy, interferon-based treatments are also commonly used for CHB. HBV RNA testing can help predict HBeAg seroconversion in patients receiving IFN-α2a therapy, serving as an early predictor of response to interferon treatment.
Therefore, HBV RNA test has significant clinical value in evaluating antiviral drug efficacy, assessing relapse risk after NA discontinuation, and early prediction of interferon treatment response.
Although strict clinical standards exist for discontinuing NA therapy, virological relapse remains common after treatment cessation. To address this challenge, researchers have focused on identifying new biomarkers and optimal timing for therapy withdrawal.
Studies indicate that patients who are double-negative for both HBV RNA and HBV DNA have a lower risk of relapse after stopping NAs, particularly among non-cirrhotic CHB patients who have already undergone treatment.
Multiple studies have shown that patients with higher levels of HBV RNA are at greater risk of developing HCC, have lower overall survival rates, and face higher recurrence risk following liver cancer surgery.
HBV RNA test not only reflects the transcriptional activity of intrahepatic HBV cccDNA—addressing the limitations of classic biomarkers like HBV DNA and HBsAg—but also complements these markers and others such as HBcrAg in providing a more comprehensive evaluation of chronic hepatitis B patients. This facilitates better monitoring and patient management, as well as clinical decision-making and prognosis assessment.
Moreover, as a serum-based biomarker, HBV RNA is easy to obtain, allows for repeat sampling, and is well-suited for dynamic observation in clinical settings—making it a highly valuable tool in precision hepatology.