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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 Apr 2016To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of the relevant data available on these agents to evaluate their effects on the estimated glomerular filtration rate (eGFR) during treatment.
METHODS
The PubMed, EMBASE, Scopus, CNKI (China National Knowledge Infrastructure), Cochrane Library, and WanFang databases were searched for relevant articles appearing in the literature up to July 1, 2015. A total of 6 studies (1960 CHB patients) with 1-year eGFR outcomes were retrieved and analyzed.
RESULTS
Generally, the results of the 6 studies analyzed showed that eGFR was improved after LdT treatment, but was decreased after ETV treatment. Using a fixed-effects approach, the change in eGFR was found to be significantly different between LdT and ETV treatment (Z = 3.64; P = 0.0003). Whereas the eGFR was slightly decreased with ETV compared with baseline (-1.45 mL/min/1.73 m(2)), the eGFR was improved with LdT (2.99 mL/min/1.73 m(2)) after 1 year of treatment. An overall test of effect in the meta-analysis showed that the eGFR in LdT-treated patients was significantly improved after 1-year of treatment (Z = 3.71; P = 0.0002).
CONCLUSION
This meta-analysis has confirmed that LdT has a renal protective effect whereas ETV does not. However, whether the benefit on renal function outweighs the occurrence of resistance in specific clinical situations is not yet clear.
Topics: Antiviral Agents; China; Guanine; Hepatitis B, Chronic; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Telbivudine; Thymidine
PubMed: 27062520
DOI: 10.1186/s12985-016-0522-6 -
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 -
Hepatology (Baltimore, Md.) Jan 2016Perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta-analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.5) at 6-12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4-8 weeks' postpartum follow-up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates.
CONCLUSIONS
Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome.
Topics: Antiviral Agents; Female; Hepatitis B, Chronic; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome
PubMed: 26565396
DOI: 10.1002/hep.28302 -
Virology Journal Sep 2012Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis,... (Meta-Analysis)
Meta-Analysis Review
Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis, approximately 10-15% of newborns from HBV carrier mothers suffer from HBV infection through intrauterine transmission. One of the risk factors is the level of maternal viraemia. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV. A few studies have evaluated the efficacy of telbivudine in preventing intrauterine HBV infection during late pregnancy. So we conducted this meta-analysis to arrive at an evidence-based conclusion. We searched Medline/PubMed, EMBASE, Cochrane Library, Web of Knowledge and China Biological Medicine Database from January 1990 to December 2011. Relative risks (RR) of the seropositivity rates for hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants were studied. Mean differences (MD) in maternal HBV DNA levels were reviewed. Finally two randomised controlled trials (RCTs) and four non-randomised controlled trials (NRCTs) were left for analysis which included 576 mothers in total, of whom 306 received telbivudine treatment and 270 did not receive any drug. All newborns received hepatitis B vaccine (HBVac) and hepatitis B immunoglobulin (HBIG) after birth. The seropositivity rate for HBsAg or HBV DNA was significantly lower in the telbivudine group, both at birth and at 6-12 months follow up. Meanwhile, maternal HBV DNA levels prior to delivery were significantly lower in the telbivudine group. In addition, the frequency of serum creatine kinase (CK) elevation was similar in the two groups. Our meta-analysis provides preliminary evidence that telbivudine application in late pregnancy is effective in the interruption of intrauterine HBV infection, with no significant adverse effects or complications. More high quality, well-designed, double-blinded, randomised controlled and large size clinical trials are needed for further investigation and more convincing results in the future.
Topics: Antiviral Agents; Female; Hepatitis B Antibodies; Hepatitis B, Chronic; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Telbivudine; Thymidine; Treatment Outcome
PubMed: 22947333
DOI: 10.1186/1743-422X-9-185 -
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 -
American Journal of Obstetrics and... Aug 2022This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.
OBJECTIVE
This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus.
DATA SOURCES
Medline, Cochrane, and Scopus databases were searched up to October 28, 2020.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included.
METHODS
Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status.
RESULTS
Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance.
CONCLUSION
A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.
Topics: Antiviral Agents; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Immunoglobulins; Infant; Infectious Disease Transmission, Vertical; Network Meta-Analysis; Pregnancy; Pregnancy Complications, Infectious; Tenofovir; Viral Load
PubMed: 35263648
DOI: 10.1016/j.ajog.2022.02.042 -
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 -
PloS One 2017HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.
METHODS
Network meta-analysis of NA treatment-induced HBeAg seroconversion after 1-2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3-5 years of treatment was systematically evaluated.
RESULTS
A total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68-23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70-16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92-2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72-1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion.
CONCLUSION
Long-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.
Topics: Antiviral Agents; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Telbivudine; Thymidine
PubMed: 28107377
DOI: 10.1371/journal.pone.0169444 -
Alimentary Pharmacology & Therapeutics Jul 2008The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of... (Review)
Review
BACKGROUND
The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.
AIM
To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses.
METHODS
A systematic review of the literature, with a focus on recent guidelines, was undertaken.
RESULTS
Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication.
CONCLUSIONS
Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.
Topics: Adenine; Antiviral Agents; Carcinoma, Hepatocellular; Deoxycytidine; Drug Resistance, Viral; Emtricitabine; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Lamivudine; Liver Cirrhosis; Nucleosides; Organophosphonates; Polyethylene Glycols; Pyrimidinones; Recombinant Proteins; Reverse Transcriptase Inhibitors; Telbivudine; Tenofovir; Thymidine; Virus Replication
PubMed: 18466358
DOI: 10.1111/j.1365-2036.2008.03731.x