Analysis Of Efficacy And Safety Of Tenofovir Amibufenamide In The Treatment Of Patients With Chronic Hepatitis B

Objective To evaluate the antiviral efficacy and safety of tenofovir amibufenamide(TMF)in treatment Na(?)ve and treatment experienced chronic hepatitis B(CHB)patients in a real-world setting,and meanwhile to compare the antiviral efficacy difference between TMF and tenofovir disoproxil fumarate(TDF)in treatment of CHB,and to provide guidance in the selection of antiviral drug treatment for CHB patients.Methods This study retrospectively collected 120 patients with CHB treated in The First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)from January 2020 to March 2022,and the diagnoses all met the diagnostic criteria of the guideline for prevention and treatment of chronic hepatitis B developed jointly by the infectious diseases branch and Hepatology branch of Chinese Medical Association in 2019,and were divided into three groups according to different treatment regimens:(1)TDF group:Initial CHB patients treated with TDF were given tenofovir dipivoxil fumarate(Chengdu Beite Pharmaceutical Co.,Ltd.,National Drug Approval Number H20163436)300 mg orally once a day.(2)TMF group:Initial CHB patients treated with TMF were given tenofovir amibufenamide(Changzhou Humon Pharmaceutical Co.,Ltd.,National Drug Approval Number H20210029)25 mg orally once a day.(3)Conversion medication group:For CHB patients who have been treated with TDF or entecavir(ETV)monotherapy,the original antiviral drug is discontinued and25 mg of amibufenamide(Changzhou Humon Pharmaceutical Co.,Ltd.,national drug approval number H20210029)is given orally once a day.The patients’general data,including gender,age,previous disease and medication history,were continuously collected until 48 weeks of follow-up,and the serum ALT levels,ALT recurrence rate,HBV DNA levels,HBV DNA negative conversion,HBs Ag,HBe Ag,serum creatinine,and e GFR were recorded for all patients at baseline,12,24,36,and 48 weeks of treatment.The changes of objective indexes before and after treatment and the effectiveness of treatment in three groups of patients were comparatively evaluated at different time nodes.Results 1.At 12,24,36,and 48 weeks of treatment,the serum ALT levels in the TMF group were 38.0(25.0,55.0)U/L,31.5(23.8,35.0)U/L,29.5(22.8,35.8,35.0)U/L,and26.0(21.8,34.8,34.0)U/L,respectively,at 12,24,24,36,and 48 weeks of treatment,compared with 38.5(25.0,60.0)U/L,30.0(22.0,44.0)U/L,31.0(22.8,44.5)U/L and28.0(19.8,44.0)U/L and(28.0,42.0)U/L ratio,none of which was statistically significant(P>0.05),and the serum HBVDNA loads in the TMF group were 0(0,3)lg IU/ml,0(0,0.5)lg IU/ml,0(0,0)lg IU/ml,and 0(0,0)lg IU/ml,respectively,compared with those in the TDF group at the 2(0,3)lg IU/ml,0(0,2)lg IU/ml,0(0,1.5)lg IU/ml,and 0(0,0)lg IU/ml ratios,which were not significantly different(P>0.05);HBs Ag levels in the TMF group were 3763.0(1960.5,10000.0)IU/m L,3682.0(2158.3,7080.3)IU/m L,3565.5(2186.8,5747.0)IU/m L,2950.0(1845.3,5760.5)IU/m L,3118.5(1645.3,5188.8)IU/m L,respectively,and there was no statistically significant difference compared to 3436.0(2085.3,5020.5)IU/m L,3262.0(1147.3,4576.8)IU/m L,2990.5(998.3,4888.8)IU/m L,2564.0(923.0,4356.3)IU/m L,2161.0(653.8,4311.3)IU/m L in TDF group(P>0.05);The seroprevalence of HBVDNA negativity in the TMF group was 58%,76%,78%and 88%,respectively,which was not significantly different from the 45%,65%,75%and 85%in the TDF group(P>0.05);At 12 weeks,24 weeks,and36 weeks of treatment,the recurrence rates of serum ALT in the TMF group were 56%,80%,and 92%,respectively,which were not significantly different from the 55%,70%,and 65%rates in the TDF group(P>0.05).At 48 weeks of treatment,the ALT recurrence rate was 100.0%in the TMF group,which was significantly higher than the rate of 72.5%in the TDF group(P<0.01);The baseline serum creatinine level of the 26 patients with complete data in the TMF group was(66.62±9.32)umol/L,which was significantly different from(63.73±11.22)umol/L at week 48(P<0.05).The baseline e GFR level was(117.00±10.76)ml/min/1.73m~2,which was not significantly different from(120.64±13.02)ml/min/1.73m~2)at 48 weeks of treatment(P>0.05).2.The ALT levels of patients in the conversion group at baseline,12,24,36,and 48 weeks of treatment were 44.50(40.00,61.25)U/L,29.00(22.75,36.50)U/L,26.50(19.00,32.25)U/L,24.50(17.30,31.00)U/L,20.00(13.75,29.75,29.25)U/L,and the median level of HBVDNA levels were 2.00(1.75,4.00)lg IU/ml,0.00(0.00,2.00)lg IU/ml,0.00(0.00,0.00)lg IU/ml,0.00(0.00,0.00)lg IU/ml and 0.00(0.00,0.00)lg IU/ml.The HBs Ag levels were 1688.00(809.00,3653.00)IU/ml,1503.00(695.50,2628.75)IU/ml,1290.00(655.25,2065.50)IU/ml,1204.00(504.50,1994.50)IU/ml,1068.50(304.50,1801.50)IU/ml,and the differences in ALT levels,HBVDNA levels,and HBs Ag levels among the above five time points were statistically significant(P<0.001).Patients in the switching medication group had 83.3%,93.3%,96.7%,100%ALT recurrences and 66.7%,86.7%,93.3%,96.7%HBVDNA negative conversion rates at 12 weeks,24 weeks,36 weeks and48 weeks of treatment,respectively(P<0.05).The baseline serum creatinine level in the switching medication group was(65.57±11.16)umol/L,which was significantly different(P<0.05)from(63.17±12.42)umol/L at 48 weeks of treatment.The baseline e GFR level of(115.18±14.98)ml/min/1.73m~2 was not significantly different from that of(115.61±13.05)ml/min/1.73m~2 at 48 weeks of treatment(P>0.05).Conclusion 1.Patients with CHB treated with TMF can achieve the same short-term efficacy as TDF,rapidly inhibiting viral replication,and improving liver function;2.Compared with TDF,TMF can achieve a higher rate of ALT normalization in newly treated patients;3.Switching to TMF for CHB patients treated with TDF and ETV can further improve the biochemical and virological response rates;TMF has shown good safety for CHB patients.