[Switching to TMF rescue therapy in patients developing low-level viremia with ETV or TAF treatment]

Objective: Some patients receiving entecavir (ETV) or tenofovir alafenamide fumarate (TAF) monotherapy may develop low-level viremia. Therefore, this study aims to observe whether switching to tenofovir alafenamide fumarate (TMF) monotherapy can further improve the efficacy of antiviral therapy in patients with chronic hepatitis B with low-level viremia. Methods: Patients with chronic hepatitis B who received ETV or TAF monotherapy for over one year were chosen. The serum HBV DNA of all patients from initiation to end fluctuated between 20-2 000 IU/ml were observed. All patients who voluntarily switched to TMF to continue antiviral treatment and completed a comprehensive examination at least once every six months were selected. The primary outcome measure was the undetectable rate of HBV DNA following six and twelve months of TMF treatment, and the secondary outcome measures were the incidence of renal tubular injury and dyslipidemia. Two independent sample t-tests or U-tests were used to compare the intergroup measurement data. The intergroup comparison of count data was performed using the χ² test or Fisher's exact probability method. Results: A total of 73 patients were included, of which 47 received ETV and 26 received TAF treatment. Among them, 33 cases were hepatitis B e antigen (HBeAg)-positive and 40 were HBeAg-negative. 69.9% (51/73) and 74.0% (54/73) of patients had HBV DNA<20 IU/ml following switching to TMF treatment for six and twelve months, respectively. Compared with HBeAg-positive patients, HBeAg-negative patients who switched to TMF treatment had a higher proportion of complete virological response (19/33 vs. 32/40, P=0.038; 18/33 vs. 36/40, P<0.001). The abnormal rate of urinary β2-microglobulin was 16.4% (12/73) after twelve months of treatment, and the proportion of patients with urinary 2-microglobulin that exceeded three times the upper limit of normal was 6.8%. The proportion of blood phosphate below the normal lower limit was 19.2% (14/73). The total cholesterol and low-density lipoprotein cholesterol levels rose compared to before therapy; however, the difference was not statistically significant. Conclusion: CHB patients receiving treatment with ETV or TAF develop low-level viremia. Therefore, switching to TMF can help most patients achieve a complete virological response and possesses good patient tolerance.