Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants

Hepatol Commun. 2023 Jul 17;7(8):e0188. doi: 10.1097/HC9.0000000000000188. eCollection 2023 Aug 1.


Background and aims: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes.

Approach results: HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare.

Conclusions: Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Nucleosides* / therapeutic use
  • Prospective Studies
  • RNA
  • Symptom Flare Up


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Hepatitis B Surface Antigens
  • Nucleosides
  • RNA