Clin Mol Hepatol > Accepted Articles
HBV pgRNA and HBcrAg reductions at week 4 predict favourable HBsAg response upon long-term nucleos(t)ide analogue in CHB
Lung-Yi Mak1,2, Danny Wong1,2, Alison Kuchta3, Martina Hilfiker4, Aaron Hamilton3, Ning Chow1, XianHua Mao1, Wai Kay Seto1,2, Man-Fung Yuen1,2
1Department of Medicine, The University of Hong Kong, Hong Kong
2State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
3Roche Molecular Systems, Inc., Pleasanton CA, USA
4Roche Diagnostics Int. AG, Rotkreuz, Switzerland
Correspondence :  Wai Kay Seto ,
Tel: (852) 22556979, Email:
Man-Fung Yuen ,
Tel: (852) 22553984, Email:
Received: June 14, 2022  Revised: July 27, 2022   Accepted: August 12, 2022
Background & Aim
s: We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).
Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36 and 48 of treatment. Patients were followed up thereafter and the serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.
Twenty-eight HBeAg-positive and 36 HBeAg-negative patients (median 38.2 years old, 71.9% male) were recruited with median follow-up duration of 17.1 (IQR 12.8-18.2) years. For the entire cohort, 22/64 (34.4%, of which 8 achieved HBsAg seroclearance) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR patients (5.49 vs 4.32 log copies/mL, respectively, p=0.016). The AUROC for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% CI 0.661-0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg from baseline in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs reduction of 2.98 log U/mL; p=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI 0.596-0.982).
Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.
KeyWords: hepatitis B virus; serum HBV pgRNA; hepatitis B core-related antigen, anti-viral treatment; functional cure
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