| Background:Hepatitis B virus(HBV)infection is a serious public health problem worldwide.Patients with chronic HBV infection may have serious complications such as liver cirrhosis(LC)and hepatocellular carcinoma(HCC).Starting antiviral therapy at the right time can not only suppress the replication of serum HBVDNA,but also delay the occurrence and development of HBV-related liver complications.Nucleoside/nucleotide analogue(NUC)is currently one of the major measures for the treatment of chronic hepatitis B(CHB).NUC can effectively suppress the replication of serum HBVDNA in CHB patients,but with the treating time prolongs,the serum HBVDNA in some patients will remain in a state of poor response and low-level viraemia(LLV)for a long time.Based on the current status of antiviral therapy for patients with chronic HBV infection,a new antiviral drug-Tenofovir alafenamide Fumarate(TAF)has been approved for the treatment of CHB patients.At the same time,the related guidelines have recommended that CHB patients with a state of poor response or LLV should switch to TAF for antiviral therapy.Therefore,this study aims to explore the efficacy and safety of switching TAF therapy in some CHB treated patients with poor NUC response or LLV status in western China.Objective:A single-center retrospective study was conducted to evaluate the efficacy and safety of switching TAF antiviral therapy in the real world in treated CHB patients with poor response or LLV status.Methods:This study retrospectively collected the data of 91 CHB treated patients who had received TAF antiviral therapy in the Outpatient Department of Hepatology Department of Lanzhou University Second Hospital from January 2019 to January 2020.All enrolled CHB treated patients were received other NUC antiviral therapy for≥48 weeks before switching TAF antiviral therapy and were in poor response or LLV status.Compare the changes in serum virological indexes,liver function indexes,kidney function indexes,complete virological response(CVR)rate,and adverse reactions at different time points(baseline,24±2w,48±2w)of the enrolled patients,who switched to TAF treatment.And then,according to the patient’s baseline serum HBVDNA load,the enrolled patients were divided into poor response group(baseline serum HBVDNA>2000IU/ml)and LLV group(20IU/ml<baseline serum HBVDNA≤2000IU/ml),and the above observation time of the two groups were compared.The difference of serum HB VDNA,serum HBsAg,serum HBeAg and CVR rates between the two groups was compared to further explore the efficacy and safety of TAF replacement therapy in CHB patients with poor response or LLV.Results:Primary endpoints:(1)Compared with the baseline,the serum HBVDNA of the enrolled patients at 24±2w and 48±2w was significantly dropped,and the difference was statistically significant in serum HBVDNA at baseline,24±2w and 48±2w(P<0.001);Compared with baseline,serum HBVDNA decreased by 44.0%and 51.8%at 24±2w and 48±2w,respectively;the CVR rates at 24±2w and 48±2w were 63.7%and 84.6%,respectively.The patients in the poor response group and the LLV group were switch to TAF for 24±2w and 48±2w serum HBVDNA decreased significantly compared with baseline.There were significant differences in serum HBVDNA between the two groups at baseline,24±2w and 48±2w(P<0.05);Compared with baseline,serum HBVDNA decreased by 64.8%and 72.0%in the poor response group at 24±2w and 48±2w,respectively;serum HBVDNA decreased by 22.6%and 30.0%in LLV group at 24±2w and 48±2w,respectively;At 24±2w and 48±2w,the CVR rates were 29.2%and 75.0%in the poor response group,respectively;and the CVR rates of the LLV group were 76.1%and 88.1%,respectively.(2)Serum HBeAg of the enrolled patients at 24±2w and 48±2w was lower than baseline,and the difference was statistically significant in serum HBVDNA between baseline,24±2w and 48±2w(P=0.013);the patients treated 22.2%and 26.7%drop range of serum HB eAg in 24±2w and 48±2w,respectively.Serum HBeAg of patients in the poor response group and LLV group was reduced compared to baseline at 24±2w and 48±2w of switching therapy,there were significant differences in serum HBeAg between two groups at baseline and 24±2w(P<0.05);the patients had treated 17.7%and 41.0%the drop range of serum HBeAg in the poor response group at 24±2w and 48±2w,respectively.The drop range of LLV group were 41.0%and 47.3%at 24±2w and 48±2w,respectively.Secondary endpoints:(1)Compared with the baseline,the serum HBsAg of the enrolled patients decreased at 24±2w and 48±2w,and there was a significant difference in serum HBsAg at baseline,24±2w and 48±2w(P<0.001).At baseline,24±2w and 48±2w,there was no significant difference in serum HB sAg between the poor response group and the LLV group(P>0.05).Compared with baseline,serum HBsAg decreased by 9.0%at 24±2w and only 5.0%at 48±2w in the poor response group,the drop range of serum HBsAg were 2.1%and 3.6%at 24±2w and 48±2w in the LLV group.(2)Compared with the baseline,the ALT and AST levels were significantly decreased at 24±2w and 48±2w,there were significant differences in ALT and AST at baseline,24±2w and 48±2w(P<0.05).Compared with baseline,the normalization rates of ALT increased by 24.2%at 48±2w,and the AST increased by 25.3.There was no statistically significant difference in the normalization rates between ALT and AST(P=0.792).(3)After switching TAF for 48±2w,the APRI score was decreased,and the difference was statistically significant(P<0.001).Safety endpoint:(1)At 48±2w,the SCr level was lower than the baseline,and the difference was statistically significant(P<0.001),the eGFR level was significantly higher than the baseline,and the difference was statistically significant(P<0.001).(2)In the process of switching TAF,the adverse reactions of the enrolled patients should mainly include fatigue,loss of appetite,facial erythema,and the incidence of adverse reactions was 3.3%.There were no serious adverse reactions or deaths due to adverse reactions.Conclusions:(1)Switching TAF for antiviral therapy in CHB treated patients with poor response or LLV status can further suppress the replication of serum HBVDNA,reduce serum HB sAg and HBeAg levels,and increase the CVR rate,(2)Switching TAF therapy in CHB treated patients with poor response or LLV status can further promote the normalization of serum transaminase and improve the patient’s renal function,(3)The safety of TAF replacement in CHB treated patients with poor response or LLV status was better,and the incidence of adverse reactions was lower. |
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