Detectability of hepatitis B virus DNA in peripheral blood mononuclear cells following long-term nucleos(t)ide analogue therapy-induced sustained viral suppression

OBJECTIVE: Hepatitis B virus (HBV) can persist in peripheral blood mononuclear cells (PBMCs) as an extrahepatic reservoir in treatment-naive patients; however, its persistence during long-term nucleos(t)ide analogue therapy with sustained serum viral suppression remains unclear. This study aimed to evaluate the frequency and predictors of HBV DNA detectability in PBMCs of chronic hepatitis B (CHB) patients following long-term nucleos(t)ide analogue therapy-induced sustained serum viral suppression. METHODS: Eighty-eight CHB patients, on long-term tenofovir disoproxil fumarate ( n = 44) or entecavir ( n = 44) with greater than 2 years of sustained viral suppression, were enrolled. PBMCs were tested for HBV DNA by quantitative PCR. Clinical and laboratory data were analyzed to identify predictors of PBMC HBV DNA detection. Receiver operating characteristic analysis assessed the performance of posttreatment serum quantitative hepatitis B surface antigen (qHBsAg). RESULTS: HBV DNA was detected in PBMCs of eight (9.1%) patients, equally distributed between treatment groups. Pretreatment hepatitis B e-antigen (HBeAg) positivity predicted PBMC HBV DNA detection ( P = 0.036). PBMC HBV DNA-positive patients were older males with worse baseline liver chemistry and advanced fibrosis. Posttreatment qHBsAg was higher in PBMC HBV DNA-positive patients (139.5 vs. 21.5 IU/ml; P < 0.001) and strongly correlated with PBMC viral load ( r = 0.905, P = 0.002); qHBsAg greater than 89 IU/ml predicted PBMC HBV DNA detection with high accuracy. CONCLUSION: HBV DNA may persist in PBMCs despite long-term nucleos(t)ide analogue therapy-induced sustained viral suppression. Pretreatment HBeAg positivity and elevated posttreatment qHBsAg can help identify patients at risk, highlighting the need to monitor extrahepatic reservoirs in CHB management.