Abstract: Objective To evaluate the long-term efficacy and safety of tenofovir alafenamide (TAF) for the real world treatment of chronic hepatitis B (CHB) patients. Methods Patients who received TAF treatment admitted to people's Hospital of Peking University from January to December 2019 were included in a single-center prospective study. The 114 patients were divided into two groups based on whether they had received treatment or not, 50 treatment-native and 94 treatment-experienced. They were followed up every 12 weeks for a total of 192 weeks. To analyze biochemical indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL); viral markers including hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA (HBV DNA); and renal function indicators including estimated glomerular filtration rate (eGFR), urinaryretinol binding protein (URBP), β2 microglobulin (β2-MG), NAG, to evaluate the therapeutic effect of TAF and its impact on kidneys and blood lipids. Results At baseline treatment-naive patients had higher levels of ALT (179.7 U/L vs 41.6 U/L, P=0.006) and AST (124.0 U/L vs 34.6 U/L, P=0.009), while those with treatment before had higher levels of albumin (45.1 g/L vs 43.5g/L, P=0.007), lower levels of HBsAg (3.37 lgIU/mL vs 3.46 lgIU/mL, P=0.029), APRI (0.60 vs 2.53, P=0.033) and eGFR [90.74 mL(min·1.73 m²) vs 98.78 mL(min·1.73 m²), P=0.010]. The virological response rates of newly treated patients at 48 weeks, 96 weeks, 144 weeks, and 192 weeks were 76%(38/50), 90%(45/50), 96%(48/50), and 100%, with the corresponding HBeAg conversion rates were 4.8%(1/21), 14.3%(3/21), 28.6%(6/21), and 33.3%(7/21), and the HBsAg negative conversion rates were 0, 0, 2%, and 2%, respectively. The virological response rates of treated patients at 48 weeks, 96 weeks, 144 weeks, and 192 weeks were 89%(84/94), 100%, 100%, and 100%, with corresponding HBeAg conversion rates of 6.7%(3/45), 17.8%(8/45), 31.1%(14/45), and 40.0%(18/45), respectively. At baseline, the HBsAg levels in treatment-naive patients were higher than those in treatment-experienced patients (4.31 lgIU/mL vs 3.97 lgIU/mL). At 96 weeks, the HBsAg levels in treatment-naive patients began to be lower compared to those in treatment-experienced patients (3.37 lgIU/mL vs 3.67 lgIU/mL). There was a significant statistical difference (P=0.01) in the degree to which the HBsAg levels in treatment-naive patients decreased from baseline between 144 and 192 weeks. Multivariate analysis showed that baseline BMI<25 kg/m²(P=0.02) and HBsAg<3.3 lgIU/mL(P=0.04) were favorable factors for a decrease of ≥0.5 log₁₀IU/mL in HBsAg at 48 weeks. The eGFR of treatment-experienced patients at all time points was lower than that of treatment-naive patients. Urinary URBP, β2MG and NAG showed no abnormal increase in the treatment-naive patients. There was no abnormal increase in URBP in treatment-experienced patients, but their β2MG and NAG increased at baseline and showed a decreasing trend with prolonged treatment time. All patients had an increase in TC from baseline at 144 weeks (4.66 mmol/L vs 4.95 mmol/L, P=0.01), and at 192 weeks (4.66 mmol/L vs 4.91mmol/L, P=0.03), but both did not exceed the upper limit of normal. Conclusion Extending the duration of TAF treatment can improve the virological response rate. TAF treatment showed a more significant decrease in HBsAg levels in treatment-naive patients, with high renal safety and no significant impact on blood lipids.

Key words: Tenofovir alafenemide, Virological response, HBsAg decrease, Kidney injury, Blood lipids