Early on-treatment HBV RNA and HBcrAg profiles predict favourable HBsAg suppression or seroclearance upon long-term nucleos(t)ide analogue therapy in CHB

Abstract

Background: We investigated the dynamics of serum HBV RNA 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). Methods: 64 patients (19 received lamivudine, 8 received adefovir, 16 received entecavir, 5 received telbivudine, and 16 received clevudine) were included. Serum HBV RNA and HBcrAg 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 at EOFU. Results: Twenty-eight HBeAg-positive and 36 HBeAg-negative patients (median 38.2 years old, 71.9% male) were recruited and the median FU duration was 16.9 years. For the entire cohort, 22/64 (34.4%, of which 8 achieved HBsAg seroclearance) achieved FHR (hepatitis B e antigen [HBeAg]-positive: 6/28 [21.4%], HBeAg-negative: 16/36 [44.4%]). For HBeAg-positive patients, serum HBV RNA decline from baseline as early as week 4 was significantly greater for patients who achieved FHR compared to non-FHR patients (-5.46 vs -4.14 log copies/mL, respectively, p=0.012) (Figure 1). The AUROC for week 4 reduction of HBV RNA to predict FHR in HBeAg-positive patients was 0.833. Using the cut-off of ≥5.32 log copies/mL drop at week 4, 62.5% patients developed FHR compared to 5.3% remaining patients. For HBeAg-negative patients, HBV RNA decline at week 4 were not significantly different between patients with FHR and non-FHR (-3.39 vs -3.11 log copies/mL, respectively, p=0.863). For HBeAg-positive patients, serum HBcrAg decline from baseline was numerically greater for FHR compared to non-FHR patients although not statistically significant (-5.21 vs -3.54 log U/mL, respectively, p=0.395). For HBeAg-negative patients, instead of increase in serum HBcrAg from baseline at week 4 in non-FHR patients, the level remained static for FHR patients (+1.37 vs 0 log U/mL, respectively, p=0.028). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.717. Using the cut-off of ≤+0.44 log U/mL increase at week 4, 62.5% patients developed favourable HBsAg response compared to 8.3% remaining patients. Conclusion: Early on-treatment changes of serum HBV RNA and HBcrAg as early as 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in CHB patients put on NAs upon long term FU.