This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We...This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.展开更多
BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alan...BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.展开更多
目的观察应用丙酚替诺福韦(TAF)继续治疗经恩替卡韦(ETV)治疗的低病毒血症(LLV)的慢性乙型肝炎(CHB)患者的疗效。方法2018年1月~2022年12月我院收治的CHB患者101例,纳入患者均接受ETV治疗至少48周,经检测符合LLV定义标准,被随机分为两组...目的观察应用丙酚替诺福韦(TAF)继续治疗经恩替卡韦(ETV)治疗的低病毒血症(LLV)的慢性乙型肝炎(CHB)患者的疗效。方法2018年1月~2022年12月我院收治的CHB患者101例,纳入患者均接受ETV治疗至少48周,经检测符合LLV定义标准,被随机分为两组,其中50例继续应用ETV治疗48周,另51例换用TAF治疗48周。常规检测血清肌酐(sCr)、β_(2)微球蛋白(β_(2)-MG)和估算的肾小球滤过率(eGFR),完全病毒学应答率(CVR)定义为血清HBV DNA载量<20 IU/mL。使用瞬时弹性成像探测仪行肝脏硬度检测(LSM)。结果在治疗48周末,TAF治疗组CVR为98.0%,显著高于ETV治疗组的24.0%(P<0.05),而两组血清HBeAg转阴率(17.7%对4.0%,P>0.05)和ALT复常率(96.1%对98.0,P>0.05)无显著性差异;TAF治疗组血清ALT、AST水平和LSM分别为(37.7±5.3)U/L、(34.8±5.7)U/L和(7.1±1.0)kPa,与ETV治疗组【分别为(36.2±4.8)U/L、(35.2±5.3)U/L和(7.8±1.1)kPa,P>0.05】比,无显著性差异;TAF组sCr和血清β_(2)-MG水平分别为(70.4±6.5)μmol/L和(1.3±0.3)mg/L,显著低于ETV治疗组【分别为(78.5±6.9)μmol/L和(1.6±0.2)mg/L,P<0.05】,而eGFR为(105.9±17.3)mL/min/1.73 m 2,显著高于ETV治疗组【(98.0±16.7)mL/min/1.73 m 2,P<0.05】。结论对于ETV经治后出现LLV的CHB患者转换为TAF继续治疗可提高病毒学应答率,安全性高,值得继续扩大验证。展开更多
Rose(Rosa chinensis),which is an economically valuable floral species worldwide,has three types,namely once-flowering(OF),occasional or re-blooming(OR),and recurrent or continuous flowering(CF).However,the mechanism u...Rose(Rosa chinensis),which is an economically valuable floral species worldwide,has three types,namely once-flowering(OF),occasional or re-blooming(OR),and recurrent or continuous flowering(CF).However,the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown.In this study,we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants.Additionally,accumulation of RcSPL1 protein was controlled by rch-miR156.The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering.Furthermore,the transient overexpression of RcSPL1 in rose plants accelerated flowering,whereas silencing of RcSPL1 had the opposite phenotype.Accordingly,the transcription levels of floral meristem identity genes(APETALA1,FRUITFULL,and LEAFY)were significantly affected by the changes in RcSPL1 expression.RcTAF15b protein,which is an autonomous pathway protein,was revealed to interact with RcSPL1.The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering,respectively.Collectively,the study findings imply that RcSPL1–RcTAF15b modulates the flowering time of rose plants.展开更多
BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is...BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is unclear.AIM To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with CHB.METHODS In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed.We used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received ETV.Compared with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV group.Body mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis.However,1-year TAF treatment did not increase the incidence of NAFLD.CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV.However,TAF-induced dyslipidemia did not increase the incidence of NAFLD.展开更多
BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel ...BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.展开更多
目的:探究富马酸丙酚替诺福韦对恩替卡韦治疗后低病毒血症慢性乙型肝炎患者的效果。方法:于2019年1月—2022年12月选取惠州市中心人民医院收治的106例低病毒血症慢性乙型肝炎患者作为研究对象,采用随机数字表法分为两组,各53例。所有患...目的:探究富马酸丙酚替诺福韦对恩替卡韦治疗后低病毒血症慢性乙型肝炎患者的效果。方法:于2019年1月—2022年12月选取惠州市中心人民医院收治的106例低病毒血症慢性乙型肝炎患者作为研究对象,采用随机数字表法分为两组,各53例。所有患者均已接受恩替卡韦抗病毒治疗,对照组继续接受恩替卡韦治疗,观察组换用富马酸丙酚替诺福韦治疗,均持续治疗24周。对比两组血清乙型肝炎病毒DNA(hepatitis B virus DNA,HBV-DNA)转阴率、乙型肝炎e抗原(hepatitis B e antigen,HBeAg)阴转率、肝功能、HBV载量、不良反应发生率。结果:治疗24周后,观察组HBV-DNA转阴率为96.23%,HBeAg转阴率为33.96%,均高于对照组的16.98%、13.21%,差异均有统计学意义(P<0.05)。两组治疗前天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、HBV载量对比,差异均无统计学意义(P>0.05);观察组治疗后AST、TBIL、ALT、HBV载量均低于对照组,差异均有统计学意义(P<0.05)。观察组不良反应发生率为7.55%,与对照组的5.66%比较,差异无统计学意义(P>0.05)。结论:富马酸丙酚替诺福韦替换恩替卡韦治疗低病毒血症慢性乙型肝炎患者可提高HBV-DNA、HBeAg阴转率,改善肝功能,降低HBV载量,安全性高。展开更多
文摘This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.
文摘BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.
文摘目的观察应用丙酚替诺福韦(TAF)继续治疗经恩替卡韦(ETV)治疗的低病毒血症(LLV)的慢性乙型肝炎(CHB)患者的疗效。方法2018年1月~2022年12月我院收治的CHB患者101例,纳入患者均接受ETV治疗至少48周,经检测符合LLV定义标准,被随机分为两组,其中50例继续应用ETV治疗48周,另51例换用TAF治疗48周。常规检测血清肌酐(sCr)、β_(2)微球蛋白(β_(2)-MG)和估算的肾小球滤过率(eGFR),完全病毒学应答率(CVR)定义为血清HBV DNA载量<20 IU/mL。使用瞬时弹性成像探测仪行肝脏硬度检测(LSM)。结果在治疗48周末,TAF治疗组CVR为98.0%,显著高于ETV治疗组的24.0%(P<0.05),而两组血清HBeAg转阴率(17.7%对4.0%,P>0.05)和ALT复常率(96.1%对98.0,P>0.05)无显著性差异;TAF治疗组血清ALT、AST水平和LSM分别为(37.7±5.3)U/L、(34.8±5.7)U/L和(7.1±1.0)kPa,与ETV治疗组【分别为(36.2±4.8)U/L、(35.2±5.3)U/L和(7.8±1.1)kPa,P>0.05】比,无显著性差异;TAF组sCr和血清β_(2)-MG水平分别为(70.4±6.5)μmol/L和(1.3±0.3)mg/L,显著低于ETV治疗组【分别为(78.5±6.9)μmol/L和(1.6±0.2)mg/L,P<0.05】,而eGFR为(105.9±17.3)mL/min/1.73 m 2,显著高于ETV治疗组【(98.0±16.7)mL/min/1.73 m 2,P<0.05】。结论对于ETV经治后出现LLV的CHB患者转换为TAF继续治疗可提高病毒学应答率,安全性高,值得继续扩大验证。
基金This work was funded by Guest Investigator Grant of the State Key Laboratory of Plant Genomics,Institute of Microbiology,Chinese Academy of Science(SKLPG2016A-29)。
文摘Rose(Rosa chinensis),which is an economically valuable floral species worldwide,has three types,namely once-flowering(OF),occasional or re-blooming(OR),and recurrent or continuous flowering(CF).However,the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown.In this study,we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants.Additionally,accumulation of RcSPL1 protein was controlled by rch-miR156.The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering.Furthermore,the transient overexpression of RcSPL1 in rose plants accelerated flowering,whereas silencing of RcSPL1 had the opposite phenotype.Accordingly,the transcription levels of floral meristem identity genes(APETALA1,FRUITFULL,and LEAFY)were significantly affected by the changes in RcSPL1 expression.RcTAF15b protein,which is an autonomous pathway protein,was revealed to interact with RcSPL1.The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering,respectively.Collectively,the study findings imply that RcSPL1–RcTAF15b modulates the flowering time of rose plants.
基金Supported by Natural Science Foundation of Fujian Province,No.2021J01123300.
文摘BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is unclear.AIM To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with CHB.METHODS In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed.We used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received ETV.Compared with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV group.Body mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis.However,1-year TAF treatment did not increase the incidence of NAFLD.CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV.However,TAF-induced dyslipidemia did not increase the incidence of NAFLD.
基金Study on the efficacy and safety of tenofovir alafenamide in treating chronic hepatitis B patients with poor entecavir response,No.SKJP22020201008.
文摘BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
文摘目的:探究富马酸丙酚替诺福韦对恩替卡韦治疗后低病毒血症慢性乙型肝炎患者的效果。方法:于2019年1月—2022年12月选取惠州市中心人民医院收治的106例低病毒血症慢性乙型肝炎患者作为研究对象,采用随机数字表法分为两组,各53例。所有患者均已接受恩替卡韦抗病毒治疗,对照组继续接受恩替卡韦治疗,观察组换用富马酸丙酚替诺福韦治疗,均持续治疗24周。对比两组血清乙型肝炎病毒DNA(hepatitis B virus DNA,HBV-DNA)转阴率、乙型肝炎e抗原(hepatitis B e antigen,HBeAg)阴转率、肝功能、HBV载量、不良反应发生率。结果:治疗24周后,观察组HBV-DNA转阴率为96.23%,HBeAg转阴率为33.96%,均高于对照组的16.98%、13.21%,差异均有统计学意义(P<0.05)。两组治疗前天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、HBV载量对比,差异均无统计学意义(P>0.05);观察组治疗后AST、TBIL、ALT、HBV载量均低于对照组,差异均有统计学意义(P<0.05)。观察组不良反应发生率为7.55%,与对照组的5.66%比较,差异无统计学意义(P>0.05)。结论:富马酸丙酚替诺福韦替换恩替卡韦治疗低病毒血症慢性乙型肝炎患者可提高HBV-DNA、HBeAg阴转率,改善肝功能,降低HBV载量,安全性高。
