Renal and bone side effects of Entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate in patients with hepatitis B: a network meta- analysis

Abstract Background As the first-line treatment for chronic hepatitis B virus infection, the long-term effects of nucleoside analogues on kidney and bone tissue damage need to be further investigated. Methods Two investigators independently searched for relevant randomized controlled trials. We included all randomized controlled trials of nucleoside analogues in the treatment of patients with chronic hepatitis B through November 2021. A random effects model was constructed on our data using stata15 software, and the standardized mean difference (SMD) and 95% confidence interval (95% CI) and surface under the cumulative ranking (SUCRA) were reported for each outcome. The side effects of the three drugs were compared. Results This study eventually included 17 studies involving 4278 adults with chronic hepatitis B. Entecavir (ETV) and tenofovir alafenamide (TAF) had less effect on estimated glomerular filtration rate (eGFR) than tenofovir disoproxil fumarate (TDF) (SMD= 3.60, 95%Cl: 1.94~5.26) and (SMD=4.27, 95%Cl :2.62~5.93). ETV had less effect on creatinine rise than TAF and TDF, SMD=0.55(95%Cl:0.09~1.01), SMD=0.61(95% Cl:0.15~1.06). The effect of TAF on bone mineral density(BMD) was less than that of TDF, with SMD=0.02 (95%Cl: 0.01~0.02). The probability of three drugs reducing relevant indicators is, eGFR: TDF(100.0%)＞ETV(41.2%)＞TAF(8.8%); BMD:TDF (79.7%)＞ETV (50.6%)＞TAF(19.6%); blood phosphorus: TDF (90.6%)＞TAF(49.8%)＞ETV(9.7%). The probability of three drugs to increase creatinine in the order: TDF (94.7%)＞TAF (54.7%) ＞ETV (0.6%). Conclusions TDF has shown stronger side effects than TAF and ETV in both renal function and bone tissue.