Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis
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SUBMITTER: Wang N
PROVIDER: S-EPMC10642028 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Background & aimsThere is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.MethodsPatients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.ResultsForty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.ConclusionsTAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.Trial registrationThis study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).
| S-EPMC8201741 | biostudies-literature
Project description:Background and aimsAntiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). No data are available on the long-term prognosis or safety of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), or entecavir (ETV) in treating HBV-ACLF globally. This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.MethodsIn this prospective, real-world cohort study, patients with HBV-ACLF were assigned to the TAF, TDF, and ETV groups. A total of 199 patients completed the 144-week follow-up. After propensity score matching (PSM), 44 patients remained in each group for further analysis of survival status, incidence of hepatocellular carcinoma (HCC), virological response, and liver and renal function indicators.ResultsIn the original cohort, HCC developed in one patient in each group. No serious drug-related adverse events were observed. In the PSM cohort, the 144-week survival rates were 56.82%, 75.00%, and 59.09% in the TAF, TDF, and ETV groups, respectively (P = 0.118). When stratified into noncirrhosis and cirrhosis subgroups at baseline, the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients (P = 0.338), and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients (P = 0.052), but the differences were not statistically significant. The long-term overall survival rates in the TAF, TDF, and ETV groups were comparable. After 144 weeks, no significant difference in the virological response rate or liver or renal function indicators was found among the three groups, except for the level of aspartate aminotransferase, which was significantly higher in the TDF group than in the ETV group at week 144 (P = 0.001).ConclusionsThere were no significant differences in the survival rate, incidence of HCC, efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registrationClinicalTrials.gov NCT03920618.
| S-EPMC11771274 | biostudies-literature
Project description:Tenofovir disoproxil fumarate (TDF) monotherapy has proven superior antiviral efficacy in chronic hepatitis B (CHB) patients; however, whether the combination of TDF and emtricitabine (FTC) exerts a significant advantage remains controversial. A meta-analysis was performed to comprehensively compare the therapeutic effects of FTC/TDF combination with TDF alone in CHB patients. Five studies involving 614 patients were identified, and subgroup analysis was performed based on the nucleos(t)ide treatment history. Our results revealed that in patients with nucleos(t)ide-naïve treatment, there were no significant differences between the treatment groups with TDF alone and FTC/TDF combination after 12 and 24 weeks; however, the FTC/TDF combination showed better viral suppression efficacy versus TDF alone after 48 (OR = 2.16, 95% CI = 1.06-4.41, P = 0.03), 96 (OR = 2.76, 95% CI = 1.29-5.92, P = 0.009) and 192 weeks (OR = 2.60, 95% CI = 1.21-5.56, P = 0.01). In patients with nucleos(t)ide treatment history, no differences were noted between the two treatment groups after 12, 24, 48 and 96 weeks. Our results indicated that FTC/TDF combination showed better viral suppression efficacy versus TDF alone in CHB patients with nucleos(t)ide-naïve treatment, while both treatments provided similar viral suppression efficacy in CHB patients with nucleos(t)ide treatment history.
| S-EPMC4499796 | biostudies-literature
Project description:Purpose Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet’s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB). Patients and Methods CHB patients with HBV-DNA <69 IU/mL after ≥24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities. Results Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was −2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; −0.8 ± 9.8 versus −2.4 ± 12.8 mL/min, respectively (P=0.017). Conclusion TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.
| S-EPMC9514787 | biostudies-literature
Project description:Background and aimsThe 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.MethodsLiterature 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.ResultsThe 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.ConclusionsThe 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.
| S-EPMC8237148 | biostudies-literature
Project description:Conflicting results have been reported regarding which of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) is associated with better outcomes. Chronic hepatitis B patients who started ETV or TDF between 2010 and 2015 were analysed. The primary outcomes were hepatocellular carcinoma and death and transplantation. The impact of the treatment on the primary outcomes was analysed using Cox proportional hazards models in the entire and propensity score-matched cohorts. A total of 404 patients (180 and 224 in the ETV and TDF groups, respectively) were analysed. The median duration of follow-up was significantly longer in the ETV group (64.0 vs. 49.1 months; P < 0.001). Virological response (79.4% vs. 68.4%; P = 0.018) and sustained virological suppression (59.7% vs. 45.2%; P = 0.005) were significantly higher in the TDF group. TDF was associated with lower hepatocellular carcinoma [hazard ratio (HR) 0.31, 95% confidence interval (95% CI), 0.12‒0.79; P = 0.014]; however, statistical significance was not reached after adjusting sustained virological suppression using propensity score matching (HR 0.36, 95% CI 0.12‒1.14; P = 0.08). Death and transplantation was comparable. In conclusion, the impact of TDF on the lower hepatocellular carcinoma was blunted after adjusting sustained virological suppression. Further comparison in a larger number of patients who show sustained virological suppression over a longer period of time is needed.
| S-EPMC7419516 | biostudies-literature
Project description:BackgroundLong-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks).AimWe assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients.MethodsPatients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks).ResultsOf 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine ≥ 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336).ConclusionsLong-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.
| S-EPMC4427621 | biostudies-literature
Project description:Background and aimsChronic hepatitis B (CHB) disproportionately affects the Asian-American population in the USA. Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity in clinical trials, but data in Asian-Americans from community studies are lacking.MethodsAdult Asian-American patients with CHB from private medical and community-based practices were prospectively enrolled and treated with open-label TDF 300 mg once daily in a single-arm study for 48 weeks. After Week 48, patients had the option to transition to commercially available CHB therapy. The primary efficacy endpoint was hepatitis B virus (HBV) DNA <400 copies/mL at Week 48. Secondary endpoints were safety and tolerability, serologic and biochemical responses, liver fibrosis by FibroTest, and the development of drug-resistant mutations.ResultsOf the 90 patients enrolled, 53 (58%) were hepatitis B e antigen (HBeAg)-positive at baseline. At Week 48, 74 patients (82% overall; 70% HBeAg-positive and 100% HBeAg-negative) had HBV DNA <400 copies/mL. Six (12%) HBeAg-positive patients achieved HBeAg loss/seroconversion. The percentage of patients with alanine aminotransferase in the normal range increased from 26% at baseline to 66% at Week 48. The percentage of patients with F0 (no or minimal) fibrosis by FibroTest increased from 48% to 51%, and those with F4 (severe) fibrosis decreased from 4% to 1%. No resistance to TDF developed. Treatment was well tolerated. Most adverse events were mild in severity and considered unrelated to study drug.ConclusionsTDF is effective and well tolerated in Asian-American CHB patients in community clinic-based settings, consistent with larger registration trials. Improvement in liver fibrosis was seen in a proportion of patients. No resistance to TDF developed through 48 weeks of treatment.Trial registrationClinicaltrial.gov identifier NCT00736190.
| S-EPMC3942404 | biostudies-literature
Project description:BackgroundTo date, a definite conclusion about efficiency and safety of tenofovir alafenamide for patients with HIV-1 is not available. The aim of the study was to investigate the efficacy and safety of TAF versus TDF in antiretroviral regimens for patients with HIV-1.MethodsPUBMED, MEDLINE, and EMBASE database were searched in March 2016, with no language restriction, for randomized controlled trials (RCTs).ResultsSix RCTs (n = 5888) met entry criteria. At week 48, viral suppression rates were similar between TAF and TDF group (90.2% vs 89.5%) for the naive patients. Interestingly, the rate was higher in patients who switched to TAF regimens compared with patients who continued previous TDF regimens (96.4% vs 93.1%). Both groups were generally well tolerated with high barrier to resistance. As compared to TDF, TAF had significantly smaller reductions in eGFR-CG, smaller changes in RBP/Cr and urineβ-2 M/Cr ratio, and less reduction in spine and hip BMD for the treatment-naive patients. Moreover, the switched group had significant efficacy advantages of improving renal function and BMD, including significant decreases in urine albumin/Cr, urine protein/Cr, urine RBP/Cr, and urine β-2 M/Cr ratios, and increases in hip and spine BMD by 1.47% and 1.56%,respectively, as compared with continued TDF regimens.ConclusionsTAF has a similar tolerability, safety, and effectiveness to TDF and probably less adverse events related to renal and bone density outcomes in the treatment of naive and experienced patients with HIV-1.
| S-EPMC5072973 | biostudies-literature
Project description: Not available
| S-EPMC10727831 | biostudies-literature