Author information

¹Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

²Immunology Research Centre, Department of Medicine (St Vincent's Hospital), The University of Melbourne, Melbourne, Victoria, Australia.

³Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

⁴Department of Public Health, La Trobe University, Melbourne, Victoria, Australia.

⁵Gastroenterology & Hepatology Unit, Monash Health, Melbourne, Victoria, Australia.

⁶Monash University, Melbourne, Victoria, Australia.

⁷Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia.

⁸Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.

⁹Central Clinical School, Monash University, The Alfred Centre, Melbourne, Victoria, Australia.

¹⁰Gastroenterology Department of Eastern Health, Melbourne, Victoria, Australia.

¹¹AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.

¹²University of Sydney, Sydney, Australia.

¹³Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, Australia.

¹⁴Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Victoria, Australia.

¹⁵Department of Gastroenterology, Bankstown-Lidcombe Hospital, Sydney, Australia.

¹⁶Department of Infectious Disease, St Vincent's Hospital Sydney, Sydney, Australia.

¹⁷Roche Molecular Systems, Inc., Pleasanton, California, USA.

¹⁸Roche Diagnostics, Pty Ltd, North Ryde, Australia.

Abstract

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.