No immediate need for nucleos(t)ide analogues treatment in untreated patients with low-level viremia: evidence from hepatitis B virus RNA levels

Introduction: Uncertainty persists regarding viral replication activity in untreated low-level viremia (LLV) patients and the need for antiviral therapy. This study compared serum HBV RNA levels in untreated LLV patients, those developing LLV post-nucleos(t)ide analogues (NAs), and patients achieving maintained virological response (MVR). Methods: A cross-sectional study enrolled untreated LLV, treated LLV, and MVR patients. Propensity score matching (PSM) minimized confounding variables. Results: Among 364 patients (61 untreated LLV, 60 treated LLV, 243 MVR), PSM analysis of 38 untreated-treated LLV pairs demonstrated significantly lower HBV RNA in untreated LLV (p < 0.001). Similarly, 1:2 PSM of untreated LLV vs. MVR (58 vs. 93 cases) revealed reduced HBV RNA in untreated LLV (p = 0.03). Conclusions: Untreated LLV patients exhibited lower HBV RNA levels than both treated LLV and MVR patients, reflecting reduced viral transcription and replication. This suggests that antiviral treatment may not be immediately necessary for this subpopulation.