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Virology Journal Sep 2010Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as lamivudine and telbivudine, are recommended for treatment of patients... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as lamivudine and telbivudine, are recommended for treatment of patients with chronic hepatitis B. However, there are no conclusive results on the comparison of the efficacy of lamivudine (LAM) and telbivudine (LdT) in the treatment of chronic hepatitis B.
RESULTS
To evaluate the comparison of the efficacy of LAM and LdT in the treatment of chronic hepatitis B by a systematic review and meta-analysis of clinical trials, we searched PUBMED (from 1990 to April 2010), Web of Science (from 1990 to April 2010), EMBASE (from 1990 to April 2010), CNKI (National Knowledge Infrastructure) (from 1990 to April 2010), VIP database (from 1990 to April 2010), WANFANG database (from 1990 to April 2010), the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review. At the end of one-year treatment, LdT was better than LAM at the biochemical response, virological response, HBeAg loss, therapeutic response, while less than at the viral breakthrough and viral resistance, but there was no significant difference in the HBeAg seroconversion and HBsAg response. LdT was better than LAM at the HBeAg seroconversion with prolonged treatment to two years.
CONCLUSIONS
In summary, LdT was superior in inhibiting HBV replication and preventing drug resistance as compared to LAM for CHB patients. But LdT may cause more nonspecific adverse events and can lead to more CK elevation than LAM. It is thus recommended that the LdT could be used as an option for patients but adverse events, for example CK elevation, must be monitored.
Topics: Antiviral Agents; Clinical Trials as Topic; Databases, Factual; Hepatitis B, Chronic; Humans; Lamivudine; Nucleosides; Pyrimidinones; Telbivudine; Thymidine; Treatment Outcome
PubMed: 20815890
DOI: 10.1186/1743-422X-7-211 -
Efficacy of telbivudine on interruption of hepatitis B virus vertical transmission: a meta-analysis.Annals of Saudi Medicine 2013Hepatitis B virus (HBV) infection is one of the most common infections in the world. Vertical transmission is the main reason for the continued endemic infection rates,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Hepatitis B virus (HBV) infection is one of the most common infections in the world. Vertical transmission is the main reason for the continued endemic infection rates, at least in Asia. This study aimed to investigate the efficacy of telbivudine on mother-to-child transmission (MTCT) interruption.
METHODS
Studies up to April 2012 were collected by searching Pubmed, EMBASE, the Cochrane Library, EBM Review, WangFang Database and China National Knowledge Infrastructure. Serum hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants, maternal HBV DNA negative conversion and alanine trans.aminase (ALT) normalization and adverse events were analyzed.
RESULTS
Seven clinical trials involving 644 pregnant women were included in this meta-analysis. Telbivudine resulted in lower HBsAg and HBV DNA seroprevalence in newborns and infants. When maternal viral load prior to delivery was higher than 103copies/mL, HBsAg or HBV DNA positivity had no statistical difference.
CONCLUSIONS
Telbivudine treatment has efficacy and safety on MTCT interruption during late pregnancy. In addition, we demonstrated benefit of telbivudine for mothers in terms of HBV DNA negative conversion and ALT normalization. Telbivudine treatment at the end of pregnancy should be considered in women with high viral load.
Topics: Antiviral Agents; Female; Hepatitis B; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Models, Statistical; Pregnancy; Pregnancy Complications, Infectious; Telbivudine; Thymidine; Treatment Outcome
PubMed: 23563007
DOI: 10.5144/0256-4947.2013.169 -
Value in Health : the Journal of the... 2012To conduct a cost-effectiveness analysis of currently available nucleos(t)ide antiviral treatments (lamivudine, telbivudine, entecavir, and tenofovir) for chronic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a cost-effectiveness analysis of currently available nucleos(t)ide antiviral treatments (lamivudine, telbivudine, entecavir, and tenofovir) for chronic hepatitis B in Canada.
METHODS
Markov modeling was used to project the lifetime health benefits and costs associated with the antiviral treatments. The hypothetical patient population was hepatitis B e antigen-positive chronic hepatitis B-infected patients aged 34 years. Quality-adjusted life-years were used as a measure of effectiveness. Long-term cumulative incidence of liver complications was also projected. Treatment effectiveness data were derived from the literature; meta-analysis was conducted when there was a large variance in reported effectiveness data. Costs were obtained from a cost analysis of treating chronic hepatitis B-related complications in Canada. Stochastic parameter uncertainty was examined in probabilistic sensitivity analysis by using second-order Monte Carlo simulation. Alternative modeling assumptions were assessed in scenario analysis. One-way sensitivity analysis was used to explore each parameter's impact on the uncertainty of the results.
RESULTS
In the base-case analysis, telbivudine was dominated by entecavir and tenofovir. Tenofovir strictly dominated lamivudine, telbivudine, and entecavir. Over the 72-year period of the model, the expected life expectancy (undiscounted) of lamivudine, telbivudine, entecavir, and tenofovir was 35.71, 36.94, 37.65, and 37.99 years, respectively. Tenofovir had the highest expected quality-adjusted life-years at 11.86 (discounted) in all comparisons. Scenario and sensitivity analyses proved the robustness of the base-case results. The projected 10-year cumulative incidence of cirrhosis and hepatocellular carcinoma was 11.40% and 3.05%, respectively, for tenofovir, which is significantly lower than that for lamivudine.
CONCLUSION
Tenofovir generated the best results compared with all other therapies under evaluation.
Topics: Adult; Antiviral Agents; Canada; Cost-Benefit Analysis; Female; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Male; Markov Chains; Quality-Adjusted Life Years
PubMed: 22999140
DOI: 10.1016/j.jval.2012.06.005 -
Advances in Therapy Apr 2016A comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
A comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B (CHB). The aim of this NMA was to assess the efficacy of telbivudine versus adefovir, entecavir, lamivudine, and tenofovir in nucleos(t)ide-naïve hepatitis B e antigen (HBeAg)-positive patients with CHB.
METHODS
A systematic review was conducted to search Medline, Medline-In Process, EMBASE, and the Cochrane Central Register of Controlled Trials databases for publications of randomized controlled trials (RCTs). NMA was performed to compare the efficacy outcomes of telbivudine versus other approved NAs at 1- and 2-year time points.
RESULTS
A total of 75 RCTs were included in the systematic review. At the 1-year time point, telbivudine was associated with significantly higher rates of: (1) HBeAg seroconversion than adefovir [odds ratio (OR) 1.99 (95% credible interval (CrI): 1.05, 3.45)], entecavir [OR 2.00 (95% CrI: 1.44, 2.82)] and lamivudine [OR 1.49 (95% CrI: 1.10, 2.03)]; (2) HBeAg loss than entecavir [OR 1.85 (95% CrI: 1.28, 2.76)] and lamivudine [OR 1.62 (95% CrI: 1.20, 2.24)]; (3) alanine aminotransferase (ALT) normalization than lamivudine [OR 1.50 (95% CrI: 1.05, 2.21)]; and (4) hepatitis B virus (HBV) DNA suppression than adefovir [OR 2.77 (95% CrI: 1.28, 5.45)] and lamivudine [OR 2.97 (95% CrI: 1.99, 4.53)]. At the 2-year time point, the relative efficacy outcomes were not statistically significant.
CONCLUSION
At 1 year, telbivudine was superior to adefovir, entecavir and lamivudine in HBeAg seroconversion, and to entecavir and lamivudine in HBeAg loss. Telbivudine was also superior to lamivudine in ALT normalization and to adefovir and lamivudine in suppressing HBV DNA levels.
FUNDING
Novartis Pharma AG.
Topics: Antiviral Agents; Comparative Effectiveness Research; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Nucleic Acid Synthesis Inhibitors; Randomized Controlled Trials as Topic; Seroconversion; Telbivudine; Thymidine; Time; Treatment Outcome
PubMed: 26921204
DOI: 10.1007/s12325-016-0305-x -
Annals of Translational Medicine Sep 2016Persistent hepatitis B virus (HBV) infections affect about 240 million patients worldwide that are at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV... (Review)
Review
Persistent hepatitis B virus (HBV) infections affect about 240 million patients worldwide that are at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double stranded DNA virus with four overlapping genes and a unique life cycle, which involves the generation of an RNA template for replication via reverse transcription. Mutations occur frequently during chronic infection, and particular selection pressures select distinct mutants. Nucleoside and nucleotide analogues like lamivudine (LMV), entecavir (ETV), telbivudine (LdT), adefovir dipivoxil (ADV) and tenofovir (TDF) are used to achieve long-term suppression of viral replication. Importantly, these drugs have different barriers to resistance, explaining the higher incidence of treatment failure in the past due to drug resistant viral strains for the older compounds LMV, LdT and ADV. On a molecular level, drug resistant mutations usually affect the reverse transcriptase domain of the HBV polymerase protein. Secondary compensatory mutations restore the replication fitness of the mutant virus. From a clinical point of view, patients undergoing antiviral therapy require regular testing for HBV DNA (every 3-6 months). In case of insufficient viral suppression or viral breakthrough (>1 log increase in HBV DNA above nadir), strict adherence to therapy needs to be ensured. If drug resistance is suspected or even molecularly confirmed, rescue therapy strategies exist, usually switching to a noncross-resistant antiviral drug. LMV, LdT and ETV resistant HBV can be treated with TDF monotherapy, ADV resistance with ETV or TDF, and insufficient responses to TDF may require ETV either as mono- or combination therapy. Complex treatment histories with many antivirals may sometimes necessitate the combination of highly effective antivirals like ETV and TDF. Novel treatment targets such as core (capsid) inhibitors, siRNA targeting protein translation, entry inhibitors or immune modulators aim at improving the efficacy of antivirals in order to (functionally) cure hepatitis B.
PubMed: 27761438
DOI: 10.21037/atm.2016.09.19 -
Gut and Liver Sep 2017Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory.... (Review)
Review
Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral suppression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous "dual" strategy, sequential combination "add-on" strategy, and "switch" strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.
Topics: Adenine; Antiviral Agents; Drug Therapy, Combination; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Nucleic Acid Synthesis Inhibitors; Organophosphonates; Telbivudine; Tenofovir; Thymidine; Treatment Outcome; Viral Load
PubMed: 28494575
DOI: 10.5009/gnl16215 -
Journal of Medical Case Reports Nov 2017Telbivudine can cause severe side effects, including myositis, neuritis, rhabdomyolysis, and lactic acidosis. However, reported cases of telbivudine leading to multiple... (Review)
Review
BACKGROUND
Telbivudine can cause severe side effects, including myositis, neuritis, rhabdomyolysis, and lactic acidosis. However, reported cases of telbivudine leading to multiple organ failure are rare. Here, we report a case of telbivudine-induced severe polymyositis, lactic acidosis, and multiple organ failure.
CASE PRESENTATION
A 30-year-old Chinese man with hepatitis B virus infection received antiviral treatment with 600 mg of telbivudine daily for more than 11 months. He developed progressive weakness and myalgia, and subsequently experienced palpitations, chest tightness, lethargy, hypotension, and hypoxemia. Blood tests showed markedly elevated levels of alanine aminotransferase (955 U/L), aspartate aminotransferase (1375 U/L), blood urea nitrogen (14.9 mmol/L), creatine kinase (peak at 8050 U/L), and blood lactate (>20.0 mmol/L). His symptoms improved after continuous renal replacement therapy and short-term methylprednisolone treatment. Hyperbaric oxygen therapy, physical therapy, and rehabilitation for more than 2 months led to recovery of muscle strength to the normal range.
CONCLUSIONS
We conclude that continuous renal replacement and steroid therapies play key roles in stabilizing telbivudine-induced severe rhabdomyolysis, lactic acidosis, and multiple organ failure. Hyperbaric oxygen, physical therapy, and rehabilitation may aid in functional recovery after the acute phase of lactic acidosis and organ failure.
Topics: Acidosis, Lactic; Adult; Antiviral Agents; Asian People; Hepatitis B, Chronic; Humans; Male; Multiple Organ Failure; Physical Therapy Modalities; Renal Replacement Therapy; Rhabdomyolysis; Telbivudine; Thymidine; Treatment Outcome
PubMed: 29179767
DOI: 10.1186/s13256-017-1498-6 -
Infectious Agents and Cancer 2019Hepatitis B caused by HBV is a serious public health hazard prevalent worldwide including Bangladesh. Few scattered molecular studies of HBV have been reported in... (Review)
Review
BACKGROUND AND AIM
Hepatitis B caused by HBV is a serious public health hazard prevalent worldwide including Bangladesh. Few scattered molecular studies of HBV have been reported in Bangladesh. This study aimed to analyze the genetic variability of RT/HBsAg overlapping region of HBV isolates of Bangladesh and determination of correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations.
METHODS
A total of 97 complete HBsAg sequences of Bangladeshi HBV isolates from 2005 to 2017 from NCBI GenBank were extracted and analyzed using several HBV bioinformatics tools such as Geno2pheno-HBV, HBV Serotyper, HIV-Grade:HBV-Tool, and CLC sequence viewer.
RESULTS
The prevalence of genotypes A, C, and D are 18, 46 and 35% which correspond to serotype , , and respectively. The prevalence of HBsAg escape mutations is 51% and most of which (62%) are found in the genotype D followed by 32% in genotype C and 6% in genotype A. Interestingly most (24/36) of the sequences of HBsAg escape mutations contained 128 V mutant which all belongs to only serotype (Genotype D). Prevalence of drug-resistant mutations is ~ 11%, most of which are from genotype C (63.64%) and D (36.36%). Lamivudine resistant mutations were found in ~ 11% of sequences followed by Telbivudine 10% and Adefovir 3% where Tenofovir showed susceptibility to all 97 sequences. Moreover, 7 among of 97 sequences showed both HBsAg and drugs resistant mutations and none of them are found due to the same nucleotide substitutions.
CONCLUSION
There is a strong correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations. This meta-analytical review will be helpful for genotype-serotype prediction by PCR-based diagnosis and development of vaccine and/or diagnostic kits, and the treatment against HBV infection in the future.
PubMed: 31709005
DOI: 10.1186/s13027-019-0253-6 -
World Journal of Hepatology Nov 2018Perinatal transmission of hepatitis B virus (HBV) infection is major contributor to the growing burden of chronic hepatitis B worldwide. Administration of HBV...
Perinatal transmission of hepatitis B virus (HBV) infection is major contributor to the growing burden of chronic hepatitis B worldwide. Administration of HBV immunoglobulin and HBV vaccination as soon after pregnancy as possible are the mainstay of prevention of perinatal transmission of HBV infection. In women with high viral loads, antiviral prophylaxis also appears to be useful. Lamivudine, telbivudine and tenofovir have been shown to be both safe and effective in this setting but tenofovir is the first-line option due to its low potential for resistance and more favorable safety profile.
PubMed: 30533180
DOI: 10.4254/wjh.v10.i11.795 -
Acta Gastro-enterologica Belgica 2019The aim of this study was to enlighten the controversy about the renal safety of entecavir, tenofovir, and telbivudine treatments in chronic hepatitis B (CHB) patients... (Comparative Study)
Comparative Study
BACKGROUND AND STUDY AIMS
The aim of this study was to enlighten the controversy about the renal safety of entecavir, tenofovir, and telbivudine treatments in chronic hepatitis B (CHB) patients by comparing these treatments in real-world conditions.
PATIENTS AND METHODS
We retrospectively enrolled 104 treatment-naive patients with CHB monoinfection into our study. Patients were treated with entecavir monotherapy (n=38), tenofovir monotherapy (n=35), or telbivudine monotherapy (n=31). We then compared and statistically analyzed the effects of these drugs on the estimated glomerular filtration rate (eGFR) over a 24-month follow-up period.
RESULTS
In the entecavir group, time-dependent change in eGFR was not statistically significant (p = 0.357). There was a statistically significant increase in eGFR in the telbivudine group at 12 months (p<0.001) and at 24 months (p<0.001) and, in contrast, a statistically significant decrease in the tenofovir group at 12 months (p<0.001) and at 24 months (p<0.001). There was no significant relationship between entecavir and eGFR change (p = 0.763). We found that tenofovir and telbivudine were independent predictors of eGFR change (decrease in eGFR, p<0.001 and increase in eGFR, p = 0.001, respectively).
CONCLUSIONS
We recommend close follow-up of renal functions, especially for patients treated with tenofovir. Telbivudine was superior to the other drugs in terms of renal function. We conclude that an individualized therapy program considering treatment efficacy and side effects is the best option for patients.
Topics: Antiviral Agents; Drug-Related Side Effects and Adverse Reactions; Female; Glomerular Filtration Rate; Guanine; Hepatitis B, Chronic; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Male; Retrospective Studies; Telbivudine; Tenofovir; Thymidine; Treatment Outcome
PubMed: 31314188
DOI: No ID Found