Effects of viral load on tenofovir vs. entecavir efficacy in recurrence prevention of hepatitis B virus-related hepatocellular carcinoma.
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SUBMITTER: Qi W
PROVIDER: S-EPMC10538913 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Effects of viral load on tenofovir vs. entecavir efficacy in recurrence prevention of hepatitis B virus-related hepatocellular carcinoma.
Qi Weili W Shen Junyi J Zhang Yu Y Gao Fengwei F Li Chuan C
Chinese medical journal 20231005 19
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Project description:IntroductionEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line therapies for chronic hepatitis B (CHB) infection. Although both drugs reduce hepatocellular carcinoma (HCC) risk, their comparative effectiveness remains controversial. We aimed to determine whether TDF is superior to ETV in preventing HCC.MethodsPubMed, Embase, and Cochrane Library from inception until June 9, 2020, were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Key terms included entecavir, tenofovir, and hepatocellular carcinoma. The adjusted hazard ratios (HRs) were pooled using a random effects model. Heterogeneity among studies was assessed by the Cochran Q test and I.ResultsThirteen observational studies (4 of which were conference abstracts) were included with 85,008 patients with CHB (ETV: 56,346; TDF: 28,662). TDF was associated with a lower HCC risk (adjusted HR [aHR]: 0.81; 95% confidence interval [CI]: 0.67-0.99). This beneficial effect was present in cirrhotic patients (aHR: 0.73; 95% CI: 0.62-0.85) and retrospective cohort studies using electronic data sets (aHR: 0.63; 95% CI: 0.51-0.78). However, this beneficial effect did not reach statistical significance for noncirrhotic patients (aHR: 0.83, 95% CI: 0.51-1.35) and retrospective/prospective cohort studies using clinical records (aHR: 0.97; 95% CI: 0.80-1.18).DiscussionTDF was associated with a lower HCC risk compared with ETV among patients with CHB, particularly cirrhotic patients. Further prospective large-scale studies with longer follow-up periods were required to identify specific subgroups that will benefit most from TDF.
| S-EPMC7544163 | biostudies-literature
Project description: Not available
| S-EPMC10727831 | biostudies-literature
Project description:BackgroundThe occurrence of hepatocellular carcinoma (HCC) is a major concern during antiviral therapy for chronic hepatitis B. There are conflicting opinions regarding the effects of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on HCC prevention. We assessed these two antiviral medications for preventing HCC in treatment-naïve patients with chronic hepatitis B.MethodsWe conducted a retrospective cohort study using nationwide claims data from the Korea Health Insurance Review and Assessment Service. We included 55,473 treatment-naïve adult cases where ETV or TDF treatment was started between 2013 and 2017 (cohort 1). The ETV and TDF groups were matched 1:2 based on age, sex, comorbidities, hospital type, and index date year. Patients were followed up until December 2018. The outcome was the development of HCC. Subgroup analyses were conducted according to sex, age, hospital type and the presence of cirrhosis. We also compared the outcomes of patients who had started antiviral therapy during the 2012-2014 period (cohort 2).ResultsThe matched participants (18,491 in the ETV and 36,982 in the TDF groups) were a part of the study for, on average, 41.2 months. The incidence of HCC did not differ significantly between the ETV (1.46 per 100 patient-years) and the TDF (1.36 per 100 patient-years) treatments (hazard ratio, 0.93; 95% confidence interval, 0.86-1.01; P = 0.081). By contrast, HCC incidence was significantly higher in the ETV group than tenofovir group of cohort 2.ConclusionIn patients with chronic hepatitis B, the ETV treatment did not result in a higher rate of HCC than the TDF treatment.
| S-EPMC8042481 | biostudies-literature
Project description:ImportanceEntecavir and tenofovir disoproxil fumarate have comparable efficacy in achieving surrogate end points, including virologic response, and are equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). However, it is unclear whether treatment with these drugs is associated with equivalent clinical outcomes, especially development of hepatocellular carcinoma (HCC).ObjectiveTo compare entecavir and tenofovir in terms of the risk of HCC and death or liver transplant in patients with CHB infection.Design, setting, and participantsA nationwide historical population cohort study involving treatment-naive adult patients with CHB who started treatment with entecavir (n = 11 464) or tenofovir disoproxil fumarate (n = 12 692) between January 1, 2012, and December 31, 2014, using data from the Korean National Health Insurance Service database. As validation, a hospital cohort of patients with CHB treated with entecavir (n = 1560) or tenofovir (n = 1141) in a tertiary referral center between January 1, 2010, and December 31, 2016, were analyzed. Nationwide cohort data were retrieved from January 1, 2010, to December 31, 2016, and hospital cohort data from January 1, 2010, to October 31, 2017.Main outcomes and measuresCumulative incidence rates of HCC and death and transplant rates.ResultsAmong the population cohort of 24 156, the mean (SD) age was 48.9 (9.8) years, and 15 120 patients (62.6%) were male. Among the hospital cohort of 2701, the mean (SD) age was 48.8 (10.5) years and 1657 patients (61.3%) were male. In the population cohort, the annual incidence rate of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years [PY]) than in the entecavir group (1.06 per 100 PY). By multivariable-adjusted analysis, tenofovir therapy was associated with a significantly lower risk of HCC (hazard ratio [HR], 0.61; 95% CI, 0.54-0.70) and all-cause mortality or transplant (HR, 0.77; 95% CI, 0.65-0.92) compared with entecavir. The tenofovir group also showed a significantly lower risk of HCC in the 10 923-pair propensity score-matched population cohort (HR, 0.62; 95% CI, 0.54-0.70) and 869-pair propensity score-matched hospital cohort (HR, 0.68; 95% CI, 0.46-0.99) compared with the entecavir group.Conclusions and relevanceThis study suggests that tenofovir treatment was associated with a significantly lower risk of HCC compared with entecavir treatment in a population-based cohort of adults with CHB; these findings were validated in a hospital cohort. Given the poor prognosis of patients with HCC, these findings may have considerable clinical implications in prevention of this cancer in patients with CHB infection.
| S-EPMC6439769 | biostudies-literature
Project description:ImportanceConventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results.ObjectiveTo perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir.Data sourcesMedline and Embase databases were searched from inception to October 6, 2021.Study selectionThe initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time.Main outcomes and measuresThe comparative risk of HCC with tenofovir vs entecavir treatment.ResultsFrom analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P < .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years.Conclusions and relevanceIn this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.
| S-EPMC9244612 | biostudies-literature
Project description:Background/aimsSuboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.MethodsThis prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.ResultsCompared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.ConclusionETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
| S-EPMC7364362 | biostudies-literature
Project description:Whether tenofovir disoproxil fumarate (TDF) is superior to entecavir in reducing hepatocellular carcinoma (HCC) risk among treatment-naïve chronic hepatitis B (CHB) patients remains controversial. We aimed to clarify this controversy. Several databases, including PubMed and Embase, were retrieved through November 2020. Cohort studies comparing the effectiveness of TDF and entecavir in reducing HCC incidence among treatment-naïve CHB patients were included if they reported multivariable-adjusted or propensity-score-matched risk estimates. A random-effects model was used to pool hazard ratios (HRs). Thirteen cohort studies, involving 4097 HCC cases and 80202 CHB patients, were included. Multivariable-adjusted meta-analysis revealed no significant difference in HCC incidence between TDF and entecavir groups (HR 0.86, 95% confidence interval 0.72-1.04), which was consistent with propensity-score-matched meta-analysis (HR 0.83, 95% confidence interval 0.66-1.03). Subgroup analysis showed that the observed similarity of TDF to entecavir for HCC prevention persisted in studies with follow-up length of ≥4 years but not in those with follow-up length of <4 years (Pinteraction<0.01). In conclusion, TDF is similar to entecavir in reducing HCC incidence among treatment-naïve CHB patients. Heterogeneous results of included studies may result from their disparity in follow-up length. Our findings should be treated with caution and need to be further confirmed.
| S-EPMC7993671 | biostudies-literature
Project description: Not available
| S-EPMC10727820 | biostudies-literature
Project description:BackgroundEntecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection.MethodsThis study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery.DiscussionThis study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study.Trial registrationClinicalTrials.gov NCT02650271. Registered on January 7, 2016.
| S-EPMC10768195 | biostudies-literature
Project description:The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.
| S-EPMC4249402 | biostudies-literature