Review on article of effects of tenofovir alafenamide and entecavir in chronic hepatitis B virus patients

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.

Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients

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.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir

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.

Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis

BACKGROUND Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir(TDF) and entecavir(ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.AIM To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.METHODS Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies(NRSs) using the keywords 'CHB', 'Tenofovir', and 'Entecavir', and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment,Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and24 mo.RESULTSNine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo[mean difference(MD) = 0.03 mg/dL;95%CI: 0.02-0.04;I2 = 0%], 12 mo(MD =0.05 mg/dL;95%CI: 0.02-0.08;I2 = 78%), and 24 mo(MD = 0.07 mg/dL;95%CI:0.01-0.13;I2 = 93%). The change in estimated glomerular filtration rate(eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo[standardized mean difference(SMD),-0.22;95%Cl:-0.36--0.08;I2 = 0%], 12 mo(SMD =-0.24;95%Cl:-0.43--0.05;I2 = 50%), and 24 mo(-0.35;95%Cl:-0.61--0.09;I2= 67%).CONCLUSION TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence.However, the differences are negligible.

Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir

Results from phase III clinical trials clearly demonstrate the efficacy and safety of entecavir and tenofovir in the controlled environment of randomized clinical studies. There are several studies with both drugs performed in clinical practice (also called &#x0201c;real life studies&#x0201d;). Despite the pros and cons, studies performed in real life conditions represent everyday practice and add important information about long term treatment effectiveness and safety in this clinical setting. This review shows that patients treated with first line nucleos(t)ide analogs at referral centres, with good clinical follow-up and adherence to international guidelines, can achieve high treatment response rates with a very low rate of adverse events.

Tenofovir is a more suitable treatment than entecavir for chronic hepatitis B patients carrying naturally occurring rtM204I mutations

BACKGROUND Hepatitis B virus(HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues(NAs), but they can occur spontaneously in treatment-na?ve chronic hepatitis B(CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs,leading to the generation of drug-resistant viral mutants and disease progression.The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear.AIM To investigate prevalence of the naturally occurring rtM204I mutations in treatment-na?ve CHB genotype C2 patients and their influence on antiviral therapy.METHODS A total of 410 treatment-na?ve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5.Complete viral response(CVR) during NAs was defined as undetectable serum HBV DNA(< 24 IU/m L). The rtM204I variants were analyzed by a newly developed locked nucleotide probe(LNA probe) based real-time PCR(LNA-RTPCR) method.RESULTS The LNA-RT-PCR could discriminate rtM204I mutant-type(17 patients, 4.2%)from rt M204 wild-type(386 patients, 95.8%) in 403 of 410 patients(98.3%sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [oddratio(OR) 3.397, 95% confidence-interval(CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment(OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations(CVR rates: patients with rtM204I, 100%;patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir(at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001).CONCLUSION The newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

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.

Factors Associated with Renal Impairment in Patients on Tenofovir for Chronic Hepatitis B in Yaoundé (Cameroon)

Background: Tenofovir (TFV) is widely used to treat patients with hepatitis B virus (HBV) infection. But kidney abnormalities are the main concern using this drug. Few studies have described the renal impairment due to the TFV in chronic hepatitis B (CHB) in Sub-Saharan Africa. The objective was to evaluate factors associated with renal impairment observed in patients on TFV for CHB. Method: It was a hospital based cross sectional prospective study carried out from June 2023 to July 2023 in Yaoundé (Cameroon) and included any patient treated with TFV for CHB during at least a period of 6 months. For each participant, we collected in the medical report socio-demographic data, clinical data, baseline creatinine, treatment information (type of TFV which was Disoproxil Fumarate (TDF) or Alafenamide (TAF), duration). Then, we collected blood samples to measure serum creatinine and phosphate levels and urine dipstick analysis. Factors associated with renal impairment were assessed with the Odds Ratio. A p value of Results: A total of 60 participants were included. The median age was 44 years [36-55] and median duration of TFV therapy was 17.5 months [11.7-25.7]. The prevalence of reduced eGFR (Conclusion: Kidney function was impaired in some patients receiving TFV for CHB. It should be monitored, particularly after 36 months and for those receiving TDF prodrug.

Chronic Hepatitis B Virus Infection: Biological Parameters in Patients Treated with Tenofovir Disoproxil Fumarate

Chronic hepatitis B causes a liver disease characterized by inflammation of the liver parenchyma. The aim of this study was to investigate the evolution of biological parameters in patients treated with Tenofovir for chronic B infection at the Commune V referral health center in Bamako. We obtained a prevalence of 14.15%. The most represented age group was 31 - 40 years, with 36.8%. The sex ratio was 1.44 in favour of men. Viral load was undetectable after 18 months of treatment in 25 patients (42.37%). Tenofovir, the 1st-line drug in Mali, is effective on the biological parameters monitored in patients.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Is tenofovir disoproxil fumarate superior to entecavir for prevention of hepatocellular carcinoma in patients with chronic hepatitis B?

Chronic hepatitis B(CHB)remains a major global health problem with approximately 258 million infected individuals(1).Hepatocellular carcinoma(HCC)is one of the major and most deadly consequences of CHB.Especially cirrhotic patients are at risk of HCC.All previous studies have also revealed a consistent association between higher hepatitis B virus(HBV)DNA levels and increased HCC risk.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Clinical Efficacy and Incidence of Adverse Reactions of Entecavir Combined with Long-Acting Interferon in Treating Hepatitis B

Objective:To explore and analyze the clinical efficacy and incidence of adverse reactions of entecavir combined with long-acting interferon in treating hepatitis B.Methods:The study was conducted from January 2020 to December 2022,and the research subjects were 69 hepatitis B patients admitted to our hospital.The patients were divided into a research group(n=35)and a control group(n=34).Patients in the control group were treated with entecavir,while patients in the study group were treated with entecavir combined with long-acting interferon.The antiviral efficacy,liver function indicators,clinical effectiveness,and incidence of adverse reactions were compared between the two groups.Results:The HBV-DNA negative conversion rate and HBeAg seroconversion rate of the patients in the study group were higher than those of the control group,and the virological breakthrough rate was lower than that of the control group(P<0.05);the alanine transaminase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)levels of the patients in the study group were all lower after treatment.In the control group,the albumin(ALB)level was higher than that in the control group(P<0.05).The clinical effective rate of patients in the study group was higher than that in the control group(P<0.05);there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The treatment effect of entecavir combined with long-acting interferon in patients with hepatitis B is significant.It can effectively antiviral and improve the liver function of patients.The incidence of adverse reactions is low and can be promoted and applied.

Network meta-analysis of the compensatory effect of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis

Objective:To evaluate the efficacy and safety of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis during the compensatory period by using mesh meta-analysis.Methods:PubMed,CNKI,Wanfang and VIP databases were searched by computer,and the retrieval time was from the establishment of each database to October 5,2022.According to inclusion and exclusion criteria,literature search was conducted independently by two researchers.RevMan5.4.1 software provided by Cochrane was used for evaluation,and Stata16.0 software was used for statistical analysis.Results:A total of 34 RCTs were included,involving 16 TCM compounds and 1543 patients.The results of network meta-analysis showed that ALT indexes of liver function were listed as Yiqi Jiedu Tongluo Method>Luoshugan Tablet>Anluo Huaxian Wan>Qishenrugan Capsule>Qingganhuaji Decoction>Ganshuang Granules>Compound Biejia Rugan Tablet>Rougan Sanjie Decoction>Shugan Jianpi Decoction>Shenqi Fuzheng Huayu Decoction>Peituhua Decoction>Shugan Jianpi Huoxu prescription>Rhubarb Zhezhan Capsule combined with Entecavir treatment respectively;The order of HA index of liver fibrosis was Heluo Shugan Tablet>Shugan Jianpi Huoxui prescription>Anluo Huaxian Wan>Compound Biejia Ruangan Tablet>Rougan Sanjie Decoction>Ganshuang Granules>Danji Huoxui Decoction>Yiqi Jiedu Tongluo Method>Rhubarb Zhezhe Capsule>Fuzheng Huayu Table>Shugan Jianpi Decoction>Rougan Huayu Decoction>Peitu Huayu Decoction>Qingganhuaji Prescription>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively;In order of adverse reactions from best to worst,Shuganjianpi Decoction,Qishenrugangan Capsule,Ganshuang Granules,Peituhuazhi Decoction,compound Biejiruganpian,and He Shugan Pian combined with entecavir,respectively;The effective rate of treatment was listed as Ganshuang Granules>Compound Biejia Ruangan Tablets>uoshugan Tablets>Rougansanjie Decoction>Rhubarb Zhezhe Capsules>Yiqi Jiedu Tongluo Method>Qingganhuaji prescription>Anluo Huaxia Wan>Shugan Jianpi Decoction>Fuzheng Huayu tablets>Peituhuazhi Decoction>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively.Conclusion:Entecavir combined with supplementing qi and detoxifying and dredging collages is the best method to recover ALT index of liver function during the compensation period for hepatitis B cirrhosis;Entecavir combination and Luoshugan tablet were the best treatment for HA index of hepatic fibrosis;Entecavir combined with Shuganjianpi Decoction was the best treatment for adverse reactions;The best treatment efficiency was Entecavir combined with Ganshuang granules.

Tenofovir Alafenamide Fumarate,Tenofovir Disoproxil Fumarate and Entecavir:Which is the Most Effective Drug for Chronic Hepatitis B?A Systematic Review and Meta-analysis

Background and Aims:The therapeutic effect of tenofovir alafenamide fumarate(TAF),tenofovir disoproxil fumarate(TDF)and entecavir(ETV)on chronic hepatitis B(CHB)patients remains inconsistent.The aim of this study was to explore the differences in virological responses to TAF,TDF and ETV in patients with CHB.Methods:Literature searches were conducted of the PubMed,EMBASE,and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21,2020.Statistical comparisons of virological response between TDF,ETV,and TAF were carried out with pooled odds ratio(OR)values.Results:The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks[OR=1.12,95%confidence interval(CI):0.89–1.41],24-weeks(OR=1.33,95%CI:1.11–1.61),48-weeks(OR=1.62,95%CI:1.16–2.25),72-weeks(OR=1.43,95%CI:0.78–2.62),and 96-weeks(OR=1.56,95%CI:0.87–2.81)treatment.No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF.The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks,48-weeks(OR=1.54,95%CI:1.17–2.02),96-weeks,and 144-weeks.Conclusions:The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients,but there was no significant difference between TAF and TDF.In addition,the therapeutic effect of TDF+ETV was superior to TDF alone.

Tenofovir disoproxil fumarate is not associated with a lower risk of hepatocellular carcinoma compared to entecavir in patients with chronic hepatitis B

A paper published several years ago suggested that tenofovir disoproxil fumarate(TDF)was superior to entecavir(ETV)for reducing the risk of hepatocellular carcinoma(HCC).Since then,many observational studies have been conducted comparing TDF and ETV.Many studies in Asia demonstrated similar HCC risks between ETV and TDF groups.Similarly,recent studies involving Caucasian and European did not observe any differences in HCC risk between these groups.In this article,we briefly review studies that compared the incidence rates of HCC between ETV and TDF and discuss potential reasons for the discrepant results.

Efficacy of tenofovir alafenamide in treatment of hepatitis B virus:A meta-analysis and non-inferiority evaluation

Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,Embase,ClinicalKey,Chinese Clinical Trial Registry and ClinicalTrials.gov from the date of inception to April 2020.The literature was screened according to the inclusion and exclusion criteria,and the efficacy evaluation index of the included RCT was set as the success rate of reaching the endpoint of viral suppression and achieving normalized ALT values at 48 weeks of treatment.Intentionality analysis was adopted and the analysis results were taken as the final conclusion.RevMan 5.3 software was used for this Meta-analysis.Meanwhile,VassarStats was used to evaluate the non-inferiority of TAF and calculate the difference of virus inhibition efficiency rate and 95%confidence interval between experimental group and the control group of each RCT.Results:After the literature search,411 potential articles were found,5 studies were finally included according to the criteria,and 2,120 patients were included.Intentionality analysis showed that TAF regimen and TDF regimen had similar viral suppression success rates(RR=0.97,95%CI:0.94~1.01,P=0.19).The ALT normalization rate in the TAF treatment group was higher than that in the TDF treatment group,and the difference was statistically significant(RR=1.35,95%CI:1.20-1.53,P<0.00001).The non-inferiority margin was set at 10%,and it was found that three RCT studies in the international multi-center all showed that TAF was not inferior to TDF in controlling HBV viral load,while two RCT studies in China's Mainland failed to achieve non-inferiority after calculation.Conclusions:At 48 weeks of treatment,TAF was similar to TDF in controlling HBV viral load.However,the efficacy of TAF in controlling HBV viral load may vary among different populations,which requires further confirmation by more clinical trial evidence.Based on AASLD criteria,the ALT normalization rate of the TAF group was higher than that of the TDF group at 48 weeks of treatment,showing an obvious advantage.

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.