-
The Lancet. Infectious Diseases Jan 2021To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614.
FINDINGS
Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis.
INTERPRETATION
Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT.
FUNDING
World Health Organization.
Topics: Adult; Antiviral Agents; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Infectious Disease Transmission, Vertical; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Tenofovir
PubMed: 32805200
DOI: 10.1016/S1473-3099(20)30586-7 -
Virology Journal Mar 2011Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as tenofovir and adefovir, are recommended for treatment of patients... (Comparative Study)
Comparative Study Meta-Analysis Review
Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as tenofovir and adefovir, are recommended for treatment of patients with chronic hepatitis B. tenofovir is a nucleoside analog with selective activity against hepatitis b virus and has been shown to be more potent in vitro than adefovir. But the results of trials comparing tenofovir and adefovir in the treatment of chronic hepatitis B were inconsistent. However, there was no systematic review on the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B. To evaluate the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B we conducted a systematic review and meta-analysis of clinical trials. We searched PUBMED, Web of Science, EMBASE, CNKI, VIP database, WANFANG database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review. Finally six studies were left for analysis which involved 910 patients in total, of whom 576 were included in tenofovir groups and 334 were included in adefovir groups. At the end of 48-week treatment, tenofovir was superior to adefovir at the HBV-DNA suppression in patients[RR = 2.59; 95%CI(1.01-6.67), P = 0.05]. While there was no significant difference in the ALT normalization[RR = 1.15; 95%CI(0.96-1.37), P = 0.14], HBeAg seroconversion[RR = 1.32; 95%CI(1.00-1.75), P = 0.05] and HBsAg loss rate[RR = 1.19; 95%CI(0.74-1.91), P = 0.48]. More high-quality, well-designed, randomized controlled, multi-center trails are clearly needed to guide evolving standards of care for chronic hepatitis B.
Topics: Adenine; Antiviral Agents; Controlled Clinical Trials as Topic; Hepatitis B virus; Hepatitis B, Chronic; Humans; Organophosphonates; Tenofovir; Treatment Outcome
PubMed: 21388525
DOI: 10.1186/1743-422X-8-111 -
Annals of Translational Medicine Sep 2022Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV)....
Comparing the efficacy and safety of tenofovir and adefovir or combined drug treatment for the treatment of chronic hepatitis B infection: a systematic review and meta-analysis.
BACKGROUND
Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV). However, the efficacy of monotherapy drug treatment is inconclusive, the safety and efficacy of TDF remain unclear, more data are needed to be included and combined drug treatment is considered to exhibit higher efficacy. To explore this issue, we performed a current literature review and meta-analysis to compare the efficacy and safety of ADV TDF, TDF ADV + lamivudine (LAM); TDF ADV + entecavir (ETV).
METHODS
We systematically searched China National Knowledge Infrastructure, the Cochrane Library, Embase, PubMed, Chinese VIP, and Wanfang Data, for relevant clinical trials since July 2015, all included studies were based on PICOS principles and evaluated independently by the reviewers in accordance with the Cochrane Handbook (Rob2.0). A meta-analysis was performed by using Review Manager 5.4.
RESULTS
We included a total of 32 studies, including 31 randomized controlled trials and one retrospective study involving 2,473 patients. The results revealed a low risk of bias in included studies, that the virologic response of TDF was superior to ADV (P<0.05). And TDF was also superior to ADV in Serum creatinine levels, Immunologic function, and safety profile. However, when ADV was combined with other medications, it was superior to TDF in alanine aminotransferase (ALT) level and Tbil level and adverse reactions, but on other indicators, TDF was superior to drug combination therapy.
CONCLUSIONS
Results showed that TDF was superior to ADV in the parameters of ALT, hepatitis B virus (HBV)-DNA reduction, HBeAg-negative conversion rate, safety, and total bilirubin levels in patients with CHB. However, when ADV was combined with LAM or ETV, they often showed the same therapeutic effect as TDF in parameters such as ALT level and Tbil level and combined therapy can effectively reduce the occurrence of adverse reactions. In this study, because the sample source countries were limited, a greater number of global studies are needed in the future to verify the current findings.
PubMed: 36267714
DOI: 10.21037/atm-22-3747 -
Health Technology Assessment... Jul 2009To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) for the... (Review)
Review
OBJECTIVE
To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) for the treatment of chronic hepatitis B (CHB).
DATA SOURCES
Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007.
REVIEW METHODS
For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs.
RESULTS
Of the 82 papers retrieved for detailed screening, eight RCTs were included. Three evaluated ADV, four evaluated PEG-alpha-2b and one (from the original literature search) compared PEG-alpha-2b plus LAM with PEG-alpha-2b monotherapy. No RCTs of PEG-alpha-2a were identified. One ADV trial showed a statistically significant difference between ADV and placebo in terms of ALT response and HBV DNA levels, favouring ADV. Following withdrawal of ADV, levels were similar to those in placebo patients. In the ADV versus ADV plus LAM trial, there was a statistically significant difference in favour of the combination treatment. In the PEG-alpha trials, there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-alpha-2b and IFN-alpha and the comparison between different staggered regimens of the commencement of PEG-alpha-2b and LAM, there were no statistically significant differences between groups. Four full economic evaluations were identified, in addition to one identified in the original report. Two assessed PEG-alpha-2a; the remainder assessed ADV. PEG-alpha-2a was associated with increased treatment costs and gains in quality-adjusted life expectancy. In a UK study, the incremental cost-effectiveness ratio (ICER) for PEG-alpha-2a was 10,444 pounds per QALY gained compared with LAM. Evaluations of ADV found that LAM monotherapy was dominated; the ICER for ADV monotherapy compared with 'doing nothing' was $19,731. The results of the updated analysis were generally robust to changes in deterministic sensitivity analysis. In a probabilistic sensitivity analysis, the same sequence of treatments was identified as optimal. In a probabilistic sensitivity analysis, PEG-alpha-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of 20,000 pounds per QALY, and 86% at a willingness-to-pay threshold of 30,000 pounds per QALY.
CONCLUSIONS
Both ADV and PEG-alpha are beneficial for patients with CHB in terms of suppressing viral load, reducing liver damage-associated biochemical activity, inducing HBeAg seroconversion, and reducing liver fibrosis and necroinflammation. The effects of long-term treatment with ADV are generally durable, with relatively low rates of resistance. In most cases, cost-effectiveness estimates were within acceptable ranges. Further research should assess the clinical effectiveness and cost-effectiveness of newer antiviral agents in relation to existing drugs, including the role of initiating treatment with combination therapy.
Topics: Adenine; Adult; Aged; Antiviral Agents; Female; Hepatitis B, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Organophosphonates
PubMed: 19607759
DOI: 10.3310/hta13350 -
Infection and Drug Resistance 2022To investigate the efficacy and safety of antiviral drugs in the treatment of coronavirus disease 2019 (COVID-19). (Review)
Review
OBJECTIVE
To investigate the efficacy and safety of antiviral drugs in the treatment of coronavirus disease 2019 (COVID-19).
METHODS
All clinical trials of antiviral drug treatment for COVID-19 from December 2019 to December 2021 in CNKI, PubMed, Embase, Wanfang and VIP databases were searched by computer, and the results were systematically reviewed.
RESULTS
A total of 21 studies were included, including 5 randomized controlled studies, 5 non-randomized controlled studies, 3 retrospective cohort studies, 6 retrospective case series studies, and 2 observational studies, with a total of 2118 patients. The evaluated drugs included Ridzevir, Lopinavir/Ritonavir, Jingluwa, Fapiravi, Abidor, Danorivir, and interferon α. The evaluated antiviral drugs did not show superior efficacy for COVID-19 in clinical trials. In terms of safety, particular attention needs to be paid to the gastrointestinal side effects of lopinavir/ritonavir and the serious side effects of redsivir.
CONCLUSION
There is no specific drug. Antiviral drugs have a greater therapeutic benefit for mild and usual patients, and in severe patients, lopinavir/ritonavir may not be effective. For critically ill patients, adefovir or more than two antiviral drugs can be used early. Antiviral drugs combined with traditional Chinese medicine treatment is effective. In view of the safety of the drug, it is necessary to consider the increase of serum uric acid caused by fapravi, the increase of bilirubin caused by abidol, and the gastrointestinal reactions of pitavir. In addition, other adverse reactions should also be noted.
PubMed: 35983302
DOI: 10.2147/IDR.S362946 -
Revista Espanola de Enfermedades... May 2016Seroclearance or seroconversion of hepatitis B surface antigen (HBsAg) is generally considered as the clinical endpoint. The purpose of the present meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
HBsAg seroclearance or seroconversion induced by peg-interferon alpha and lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a meta-analysis and systematic review.
BACKGROUND AND AIMS
Seroclearance or seroconversion of hepatitis B surface antigen (HBsAg) is generally considered as the clinical endpoint. The purpose of the present meta-analysis was to evaluate pegylated interferon alpha (PEG-IFNα) with or without lamivudine (LAM) or adefovir (ADV) combination treatment in HBsAg seroclearance or seroconversion with CHB.
METHODS
Randomized controlled trials of adults with CHB prior to May 30th 2015, with 48-52 weeks of PEG-IFNα and LAM or ADV combination therapy or monotherapy, were included. Review Manager Software 5.2.0 was used for meta-analysis.
RESULTS
No statistical difference was noticed in HBsAg seroclearance (9.9% vs 7.1%, OR = 1.47, 95% CI 0.75, 2.90; p = 0.26) or observed in HBsAg seroconversion (4.2% vs 3.7%, OR = 1.17, 95% CI 0.57, 2.37; p = 0.67) between PEG-IFNα + LAM and PEG-IFNα + placebo for 24-26 weeks follow-up after treatment on hepatitis B e antigen (HBeAg)-positive CHB. Statistical difference was not showed in HBsAg disappearance (10.5% vs 6.4%, OR = 1.68, 95% CI 0.75, 3.76; p = 0.21) but was demonstrated in HBsAg seroconversion (6.3% vs 0%, OR = 7.22, 95% CI 1.23, 42.40; p = 0.03) between PEG-IFNα + ADV and PEG-IFNα for 48-52 weeks treatment on HBeAg-positive CHB By systematical evaluation, there were no differences in HBsAg disappearance and seroconversion between PEG-IFNα + placebo and PEG-IFNα + LAM for 48-52 weeks treatment on HBeAg-positive CHB. There were no differences in HBsAg disappearance and seroconversion between PEG-IFNα + placebo and PEG-IFNα + LAM during 24 weeks to 3 years follow-up after treatment on HBeAg-negative CHB by systematical evaluation.
CONCLUSION
The combination between PEG-IFNα and LAM or ADV was not superior to monotherapy of PEG-IFNα in terms of HBsAg seroclearance or seroconversion.
Topics: Adenine; Antiviral Agents; Drug Therapy, Combination; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Organophosphonates; Reverse Transcriptase Inhibitors; Seroconversion
PubMed: 27023755
DOI: 10.17235/reed.2016.3995/2015 -
The Brazilian Journal of Infectious... 2013The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic... (Review)
Review
The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.
Topics: Adenine; Antiviral Agents; Brazil; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Male; Markov Chains; Organophosphonates; Polyethylene Glycols; Recombinant Proteins; Tenofovir
PubMed: 23849851
DOI: 10.1016/j.bjid.2012.12.005 -
Health Technology Assessment... Aug 2006To assess the clinical effectiveness and cost-effectiveness of adefovirdipivoxil (ADV) and pegylated interferon alfa-2a (PEG) for the treatment of adults with chronic... (Comparative Study)
Comparative Study Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of adefovirdipivoxil (ADV) and pegylated interferon alfa-2a (PEG) for the treatment of adults with chronic hepatitis B infection (CHB).
DATA SOURCES
Electronic databases for the period from 1995-6 to April 2005. Websites of the relevant organisations.
REVIEW METHODS
Searches were made for studies of clinical effectiveness, cost-effectiveness, quality of life, resource use/costs and epidemiology/natural history. Randomised controlled trials (RCTs) were included that compared PEG and ADV with currently licensed treatments for CHB, including non-pegylated ('standard') interferon alfa (IFN), lamivudine (LAM), and best supportive care. The trials were reviewed in a narrative synthesis but meta-analysis was not undertaken owing to heterogeneity in the interventions and comparators evaluated. A model was developed to estimate the cost-effectiveness (cost-utility) of PEG and of ADV compared with IFN, LAM and best supportive care in a UK cohort of adults with CHB. The perspective of the cost-effectiveness analysis was that of the NHS and personal social services. A Markov state transition model was constructed, informed by a systematic search of the literature to identify source material on the natural history, epidemiology and treatment of CHB. Interventions were evaluated against their closest comparator (for PEG this is IFN, and for ADV this is LAM). In addition, the cost-effectiveness of sequential treatment scenarios was modelled.
RESULTS
A total of 1086 references to clinical effectiveness studies were identified, of which seven fully published RCTs and one systematic review met the inclusion criteria. Four of the RCTs evaluated the effectiveness of ADV and three reported results for PEG. In addition, a conference abstract was included reporting interim results from an on-going Phase II RCT of ADV in combination with LAM. The published trials were of good quality, although details of randomisation and allocation of concealment were poorly reported. ADV was significantly more effective than placebo. Response rates were in the range 21-51% compared with 0%, respectively. For patients resistant to LAM, response rates were significantly higher for those treated with ADV in addition to on-going LAM (35-85%) than those who continued on LAM with placebo (0-11%). Significant alanine aminotransferase (ALT) reductions to normal levels were observed in all studies. For treatment-naive patients, seroconversion rates were 12-14% for ADV compared with 6% for placebo (statistically significant), rates were higher for LAM-resistant patients who received ADV in addition to on-going LAM (8%) than those who continued on LAM with placebo (2%) (no significance value was reported), and rates were higher for LAM-resistant patients who switched to ADV than those who continued on LAM with placebo (11 versus 0%, respectively; not statistically significant). HBsAg loss or seroconversion was observed in less than 5% of patients taking ADV. Two ADV studies reported changes in liver histology. In general, histological improvement and necroinflammatory activity/fibrosis scores were significantly better in ADV groups than in placebo groups. Dose discontinuations for safety reasons were low for patients receiving ADV. With the exception of headache, the most commonly reported adverse events were often seen in the placebo groups in similar proportions to the ADV groups, with different trials reporting conflicting results. PEG/LAM dual therapy and PEG monotherapy were similar in effect on HBV DNA and ALT levels, and both were significantly superior to LAM monotherapy. Response rates were higher for HBeAg-negative patients than for HBeAg-positive patients. HBeAg seroconversion rates at follow-up were significantly higher for PEG monotherapy patients than for those receiving either a combination of PEG and LAM or LAM monotherapy (32, 27 and 19%, respectively). For the comparison between PEG and IFN-2a, there was a significant difference in the combined outcome of ALT normalisation, HBV DNA response and HBeAg seroconversion at follow-up (24 versus 12%, respectively). Changes in liver histology were reported by two studies. There was no statistically significant difference in histological improvement between the PEG monotherapy groups, the LAM monotherapy groups and the dual therapy groups. Two PEG trials reported small percentages (up to 5%) of HBsAg loss or seroconversion among patients receiving PEG either as monotherapy or in combination with LAM, but no HBsAg loss or seroconversion was reported in those receiving LAM monotherapy. Health-related quality of life (HRQoL) scores, as measured by the Short Form with 36 Items, decreased during treatment, but returned to at least baseline levels at follow-up (based on unpublished data). For HBeAg-positive patients, there were no significant differences in scores between treatment groups. Dose discontinuations for safety reasons were significantly higher for patients receiving PEG than for patients receiving LAM monotherapy. The most commonly reported adverse events in the PEG studies were headache, pyrexia, fatigue, myalgia and alopecia. Only one fully published economic evaluation was identified, reporting a US cost-effectiveness study of ADV as salvage therapy for chronic hepatitis B with LAM resistance. A Markov model was used to estimate cost-effectiveness of interferon alfa (6-12 months), LAM and LAM followed by ADV when resistance occurs. ADV generated the most (undiscounted) life-years, but at highest costs, with an incremental cost-effectiveness ratio (ICER) of US$14,204 per life-year gained. Using our model, incremental cost per QALY estimates (baseline cohort of all patients) were: 5994 pounds for IFN compared with best supportive care, 6119 pounds for PEG compared with IFN, 3685 pounds for LAM compared with best supportive care, and 16,569 pounds for ADV compared with LAM. Incremental cost per QALY estimates (HBeAg-positive patients only) were: 7936 pounds for IFN (24 weeks) compared with best supportive care, 16,166 pounds for PEG (48 weeks) compared with IFN (24 weeks), 3489 pounds for LAM compared with best supportive care, and 15,289 pounds for ADV compared with LAM. Incremental cost per QALY estimates (HBeAg-negative patients only) were: 3922 pounds for IFN (48 weeks) compared with best supportive care, 2162 pounds for PEG (48 weeks) compared with IFN (24 weeks), 4131 pounds for LAM compared with best supportive care, and 18,620 pounds for ADV compared with LAM. For the sequential treatment strategies, incremental cost per QALY estimates ranged from 3604 pounds (IFN followed by LAM versus IFN alone) to 11,402 pounds (IFN followed by LAM with adefovir salvage versus IFN followed by LAM). In all of these cases, the ICERs are well within the range that would conventionally be regarded as being cost-effective. The probabilistic sensitivity analysis found that LAM is a cost-effective option at lower willingness-to-pay thresholds for health outcomes, but as the threshold is increased adefovir is increasingly likely to be the optimal intervention. Where a willingness-to-pay threshold of above 10,000 pounds per QALY is employed, PEG is highly likely to be the optimal intervention compared with IFN (based on a cohort of HBeAg-positive and -negative patients). Interferon alfa (non-pegylated or pegylated) followed by LAM would be the optimal strategy at lower willingness-to-pay thresholds. As the threshold increases, the sequential treatment strategy of PEG followed by LAM with adefovir added as salvage therapy is increasingly likely to be the optimal intervention.
CONCLUSIONS
ADV and PEG are associated with significant improvements in a number of biochemical, virological and histological outcomes in both HBeAg-positive and -negative patients. For a small proportion of patients this is associated with resolution of infection. For another proportion it leads to remission and a reduced risk of progressing to cirrhosis, hepatocellular carcinoma, liver transplant and death. For others who do not respond or who relapse, retreatment with another agent is necessary. The results of our cost-effectiveness analysis demonstrate that incremental costs per QALY for a range of comparisons were between 5994 pounds and 16,569 pounds and within the range considered by NHS decision-makers to represent good value for money. When subjected to sensitivity analysis, most costs per QALY estimates remained under 30,000 pounds. Further RCT evidence of the effectiveness of anti-viral treatment is required, particularly for subgroups of patients with different genotypes, patients with cirrhosis, patients from different ethnic groups, patients with co-infections (e.g. HIV, HCV) and co-morbidities, liver transplant patients and children and adolescents.
Topics: Adenine; Antiviral Agents; Cost-Benefit Analysis; Drug Carriers; Drug Therapy, Combination; Health Services; Hepatitis B, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Organophosphonates; Patient Selection; Polyethylene Glycols; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 16904047
DOI: 10.3310/hta10280 -
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 -
Virology Journal Aug 2011Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance.
METHODS
We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed.
RESULTS
Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated.
CONCLUSIONS
LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.
Topics: Adenine; Antiviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; Guanine; Hepatitis B, Chronic; Humans; Lamivudine; Liver Function Tests; Organophosphonates; Salvage Therapy; Time Factors; Treatment Outcome; Viral Load
PubMed: 21824397
DOI: 10.1186/1743-422X-8-393