Dataset Information

The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis.

ABSTRACT:

Background

It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes.

Methods

Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis.

Results

Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P?=?0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P?=?0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P?=?0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P?=?0.37] between the two groups.

Conclusion

There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6542001 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis.

Zhang Zeyu Z Zhou Yufan Y Yang Jiajin J Hu Kuan K Huang Yun Y

BMC cancer 20190529 1

<h4>Background</h4>It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir mo ...[more]

PMID: 31142283

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Project description:Background & aimsPatients chronically infected with the hepatitis B virus (HBV) and receiving long-term treatment with nucleoside or nucleotide analogues are at risk of selecting HBV strains with complex mutational patterns. We herein report two cases of HBV-infected patients with insufficient viral suppression, despite dual antiviral therapy with entecavir (ETV) and tenofovir (TDF). One patient died from aggressive hepatocellular carcinoma (HCC).MethodsSerum samples from the two patients at different time points were analyzed using ultra-deep pyrosequencing analysis. HBV mutations were identified and transiently transfected into hepatoma cells in vitro using replication-competent HBV vectors, and functionally analyzed. We assessed replication efficacy, resistance to antivirals and potential impact on HBV secretion (viral particles, exosomes).ResultsSequencing analyses revealed the selection of the rtS78T HBV polymerase mutation in both cases that simultaneously creates a premature stop codon at sC69 and thereby deletes almost the entire small HBV surface protein. One of the patients had an additional 261bp deletion in the preS1/S2 region. Functional analyses of the mutations in vitro revealed that the rtS78T/sC69∗ mutation, but not the preS1/S2 deletion, significantly enhanced viral replication and conferred reduced susceptibility to ETV and TDF. The sC69∗ mutation caused truncation of HBs protein, leading to impaired detection by commercial HBsAg assay, without causing intracellular HBsAg retention or affecting HBV secretion.ConclusionsThe rtS78T/sC69∗ HBV mutation, associated with enhanced replication and insufficient response to antiviral treatment, may favor long-term persistence of these isolates. In addition to the increased production of HBV transcripts and the sustained secretion of viral particles in the absence of antigenic domains of S protein, this HBV mutation may predispose patients to carcinogenic effects.Lay summaryLong-term treatment with antiviral drugs carries the risk of selecting mutations in the hepatitis B virus (HBV). We herein report two cases of patients with insufficient response to dual tenofovir and entecavir therapy. Molecular analyses identified a distinct mutation, rtS78T/sC69∗, that abolishes HBsAg detection, enhances replication, sustains exosome-mediated virion secretion and decreases susceptibility to antivirals, thereby representing a potentially high-risk mutation for HBV-infected individuals.

Project description:Objective: We conducted a network meta-analysis to comprehensively compare various anticancer agents used in transarterial chemoembolization (TACE) based on the Bayesian theorem. Methods: Globally recognized electronic databases, including PubMed, EMBASE, and Cochrane Central, were searched to retrieve relevant randomized controlled trials (RCTs) comparing anticancer agents in TACE for hepatocellular carcinoma (HCC) patients. The therapeutic response, adverse events and overall survival rate were selected as parametric data to evaluate the clinical efficacy. Quantitative network meta-analysis and pair-wise analysis were conducted to compare the relative parameters. Results: Of the 4242 retrieved articles, 17 RCTs containing 2330 patients fulfilled the inclusion criteria. The network meta-analysis exhibited that the application of anthracycline and mitomycin plus pyrimidine presented the best clinical values regarding all parametric data (probability P=0.45, 0.32 and 0.35 regarding comparison of response rate, adverse event and overall survival, respectively). Accordingly, further investigation on specific anticancer agents indicated that the combination of doxorubicin and mitomycin plus gemcitabine was the best agent combination in TACE (probability P=0.49, 0.37 and 0.77 regarding comparison of response rate, adverse event and overall survival, respectively). Moreover, an additional study indicated that the single use of an anticancer agent prior to embolism brought no benefit compared with bland embolism without any agent (Test Z=0.15, 0.84, 1.22 and P=0.88, 0.40, 0.22 regarding comparison of response rate, adverse event and overall survival, respectively). However, the combined use of anticancer agents in TACE showed significantly better clinical efficacy than single use (Test Z=4.40, 3.94, 0.24 and P<0.001, <0.001, =0.81 regarding comparison of response rate, adverse event and overall survival, respectively); thus, combination utilization was recommended. Conclusions: The combined use of anticancer agents in TACE was recommended. Application of anthracycline and mitomycin plus pyrimidine seemed to be the best choice for clinical consideration. Additionally, the combination of doxorubicin and mitomycin plus gemcitabine may be the best specific anticancer agent combination in TACE currently, although additional RCTs are expected to support our conclusion.

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Project description:BackgroundA series of studies has investigated the prognostic role and clinical significance of programmed death ligand 1 (PD-L1) in hepatocellular carcinoma (HCC). However, the results were inconsistent. We aimed to clarify the prognostic role of PD-L1 and relationship between PD-L1 expression and several important clinicopathological features.MethodsPubMed, EMBASE and the Science Citation Index Expanded were systematically searched. All cohort or case-control studies comparing the prognosis and clinical features between the high PD-L1 and low PD-L1 groups were included. Publication bias was evaluated using funnel plots and Begg's test. Subgroup analysis, sensitivity analysis and meta-regression analysis were performed.ResultsSeventeen studies including 2979 patients were eligible. The overall survival (OS) was not significantly different between the high and low PD-L1 groups (hazard ratio [HR]: 1.27; 95% confidence interval [CI] 0.98-1.65: P = 0.07) with significant heterogeneity (P < 0.001; I2 = 81%). The recurrence-free survival (RFS) was not significantly different between the high and low PD-L1 groups (HR: 1.22; 95% CI 0.97-1.53; P = 0.09) with significant heterogeneity (P < 0.001; I2 = 78%). The expression of PD-L1 was found to be significantly correlated with alpha-fetoprotein, hepatitis history, and tumour-infiltrating lymphocytes. Begg's test found no significant publication bias for OS and RFS. Sensitivity analysis established the robustness of our results. Subgroup analysis and meta-regression analysis found the region of research as a significant contributor to inter-study heterogeneity in RFS, indicating some racial differences in the prognostic role of PD-L1.ConclusionsOur study found no significant prognostic role of PD-L1 in HCC patients after potential curative hepatectomy based on our included studies. The expression of PD-L1 was significantly correlated with AFP, hepatitis history, and TILs. The prognostic role of PD-L1 in HCC warrants further investigation.

Dataset Information

The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis.

Background

Methods

Results

Conclusion

Publications

The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis.

Similar Datasets

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