Abstract: Objective The aim of this study was to investigate the efficacy of switching from entecavir(ETV) or tenofovir(TDF) to other different antiviral therapy in ETV- or TDF-treated chronic hepatitis B (CHB) patients with low-level viraemia (LLV). Methods A total of 197 patients with CHB who had been treated with ETV or TDF were enrolled in this study and were divided into group A (n=74) continuing ETV or TDF treatment, group B( n=63) switching to TAF therapy and group C (n= 60) switching to ETV or TDF and peg-IFNα-2b combination therapy. The regimen lasted for (48±2) weeks. Results At the end of 48 week treatment, the complete virologic response and serum HBeAg negative rates in group C were 90.0% and 41.7%, significantly higher than 16.2% and 5.4%(P<0.05) in group A or 66.7% and 9.5%(P<0.05) in group B, and serum ALT normalization rates in group B and group C were 20.6% and 23.3%, significantly higher than 8.1%(P<0.05) in group A; serum HBsAg level in group C was 3.0(2.8, 3.4)lgIU/ml, significantly lower than [3.3(2.9, 3.9)lgIU/ml, P<0.05] in group A or [3.4(3.3, 3.8)lgIU/ml, P<0.05] in group B, serum HBeAg level was 0.1(-0.7, 0.0)lgIU/ml, significantly lower than [0.6(-0.6, 1.8) lgIU/ml, P<0.05] in group A or [0.6(-0.3, 1.8)lgIU/ml, P<0.05] in group B, and serum HBV DNA load was 1.3(1.3, 1.3)lgIU/ml, significantly lower than [1.7(1.3, 2.0)lgIU/ml, P<0.05] in group A or [1.6(1.3, 1.4)lgIU/ml, P<0.05] in group B; the LSMs in group B and group C were 6.4(4.3, 8.4) kPa and 6.2(4.2, 7.7) kPa, both significantly lower than [8.6(5.2, 10.7) kPa, P<0.05] in group A, and serum ALT levels in the three groups were not significantly different (P＞0.05). Conclusion The switch to TAF or combined with peg-IFNα-2b therapy in ETV- or TDF-treated patients with LLV might benefit for further virologic and even serologic response, and warrants clinical investigation.

Key words: Hepatitis B, Low-level viremia, Tenofovir disoproxil fumarate, Peg-interferon α-2b, Switching therapy