HBeAg-positive patients with HBsAg  < 100 IU/mL and negative HBV RNA have lower risk of virological relapse after nucleos(t)ide analogues cessation

Abstract

Background Nucleos(t)ide analogues (NAs) cessation is not widely practiced and remains a controversial, but highly relevant subject in patients infected with hepatitis B virus (HBV). We aimed to explore the related factors for safe NAs cessation. Methods This is a multicenter prospective cohort study. Overall, 139 initially HBV e antigen (HBeAg)-positive patients meeting the stopping criteria were included in 12 hospitals in China. Enrolled patients ceased NAs and were followed up every 3 months for 24 months or until clinical relapse (CR). Results The 24 month cumulative rates of virological relapse (VR), CR, HBeAg reversion and HBV surface antigen (HBsAg) loss were 50.4, 24.5, 11.5 and 9.4%, respectively. Patients with end of treatment (EOT) HBsAg &lt; 100 IU/mL plus negative HBV RNA had the lowest 24 month cumulative VR rate (5 vs 58%, p &lt; 0.001). EOT HBsAg ≥ 2 log10 IU/mL [odds ratio (OR) = 6.686, p = 0.006], EOT positive HBV RNA (OR = 3.453, p = 0.008) and EOT hepatitis B core-related antigen (HBcrAg) ≥ 4log U/mL (OR = 3.702, p = 0.002) were found to independently predict the risk of VR. To predict VR, the area under the receiver-operating characteristic (AUROC) value of the EOT HBsAg &lt; 100 IU/mL plus EOT HBV RNA negative was 0.698 (p &lt; 0.001), which was higher than other parameters alone or combinations. Conclusions NAs cessation is suitable only for a small and selected patients. An EOT HBsAg &lt; 100 IU/mL and EOT negative HBV RNA identified a patient with low risk of off-treatment VR.

Serum Pregenomic RNA Combined With Hepatitis B Core-Related Antigen Helps Predict the Risk of Virological Relapse After Discontinuation of Nucleos(t)ide Analogs in Patients With Chronic Hepatitis B

“…Serum HBsAg levels correlate with hepatic cccDNA activity and the loss of serum HBsAg is an ideal indicator to evaluate safety discontinuation. Previous studies have shown that EOT serum HBsAg levels are an independent risk factor for VR, but predominantly at low levels, with EOT HBsAg >100 or >40 IU/L ( Hsu et al, 2019 ; Fan et al, 2020 ; Tseng et al, 2020 ; Xie et al, 2021 ). In our study, although EOT HBsAg was not significantly associated with VR, patients with EOT HBsAg ≤100 IU/mL had a lower rate of VR than those with EOT HBsAg >100 IU/mL [28.6% (2/7) vs. 54.4% (31/57), p = 0.197], which is consistent with the results of previous studies.…”

Review article: novel biomarkers in hepatitis B infection

“…6.686, 95% CI 1.703-26.255), or detectable HBV RNA (OR 3.453, 95% CI 1.387-8.597, p = 0.008). 106 In a similar study comprising HBeAg-negative individuals, virological relapse occurred in 54.4% of individuals within 1 year of stopping nucleoside analogues, and an end-of-treatment HBcrAg level >3.7 log 10 IU/ml was strongly associated with this risk (OR 3.751, 95% CI 1.187-11.856, p = 0.024). 107 Combining HBcrAg with other viral biomarkers may allow a more accurate prediction of relapse; in an analysis of 185…”

Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued

“…Circulating viral markers including HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA, are proposed as markers for possible treatment cessation because of their close association with active transcription and cccDNA replication. 6 , 7 However, an understanding of the immunological factors that contribute to a sustained off-treatment response is limited.…”