Background Treatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment cessation suitability has not been well-investigated.
Methods Nucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.
Results 114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.
Conclusion Serum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.
Trial registration number NCT02738554
- nucleoside analogue
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Correction notice Thsi article has been corrected since it published Online First. Figure 2D and supplementary figure 3A have been amended.
Contributors W-KS was involved in involved in study concept and design, securing research funding, acquisition of data, analysis and interpretation of data and drafting of manuscript. KL was involved in study concept and design and acquisition of data. LYM, FY-FL, K-SC, K-LK and W-PT were involved in acquisition of data. GC and JG were involved in acquisition of data and analysis and interpretation of data. DK-HW and NC were involved in acquisition of laboratory measurements. JF was involved in securing research funding and critical revision of manuscript. M-FY was involved in study concept and design, analysis and interpretation of data, critical revision of manuscript and overall study supervision.
Funding This study was conducted in collaboration with Abbott Diagnostics with two coauthors being Abbott Diagnostics employees. This study was also supported by the Innovative Research Fund of the State Key Laboratory of Liver Research, The University of Hong Kong (ref. no.: SKLLR/IRF/2018/07) and the S. K. Yee Medical Foundation Grant (ref. no.: 2141213). Serum HBcrAg measurements were supported by Fujirebio Incorporation.
Competing interests GC and JG are Abbott Diagnostics employees and hold Abbott stocks. W-KS received speaker’s fees from Mylan, is an advisory board member and received speaker’s fees from AbbVie, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. JF is an advisory board member of Gilead Sciences. M-FY is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol-Myers Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation. The remaining authors have no conflict of interests.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The present study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster. Informed written consent was obtained from all participants.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. Bona fide biomedical researchers from recognised research institutions can request deidentified data sets by emailing the corresponding author.
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