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Clinical Gastroenterology and... Jan 2018We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus infection who achieved a sustained virologic response (SVR).
METHODS
We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with hepatitis C virus infection who received antiviral therapy (either direct-acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR. We identified 24 studies, and estimated weighted mean difference (and 95% confidence interval) in liver stiffness in patients with versus without SVR using random-effects meta-analysis.
RESULTS
In patients who achieved SVR, liver stiffness decreased by 2.4 kPa at the end of therapy (95% CI, -1.7 to -3.0), by 3.1 kPa 1-6 months after therapy (95% CI, -1.6 to -4.7), by 3.2 kPa 6-12 months after therapy (90% CI, -2.6 to -3.9), and 4.1 kPa 12 months or more after therapy (95% CI, -3.3 to -4.9) (median decrease, 28.2%; interquartile range, 21.8-34.8). In contrast, there was no significant change in liver stiffness in patients who did not achieve an SVR (at 6-12 months after therapy, decrease of 0.6 kPa; 95% CI, -1.7 to 0.5). Decreases in liver stiffness were significantly greater in patients treated with direct-acting antiviral agents than with interferon-based therapy (decrease of 4.5 kPa vs decrease of 2.6 kPa; P = .03), cirrhosis at baseline (decrease of 5.1 kPa vs decrease of 2.8 kPa in patients with no cirrhosis; P = .02), or high pretreatment levels of alanine aminotransferase (P < .01). Among patients with baseline liver stiffness >9.5 kPa, 47% (95% CI, 27%-68%) achieved posttreatment liver stiffness of <9.5 kPa.
CONCLUSIONS
In a systematic review and meta-analysis, we associated eradication of hepatitis C virus infection (SVR) with significant decreases in liver stiffness, particularly in patients with high baseline level of inflammation or patients who received direct-acting antiviral agents. Almost half the patients considered to have advanced fibrosis, based on VCTE, before therapy achieved posttreatment liver stiffness levels <9.5 kPa. Clinical Trial Registration no: CRD42016051034.
Topics: Antiviral Agents; Elasticity Imaging Techniques; Hepatitis C, Chronic; Humans; Liver; Sustained Virologic Response; Time Factors; Treatment Outcome
PubMed: 28479504
DOI: 10.1016/j.cgh.2017.04.038 -
Dermatology Online Journal Mar 2020New treatment options for warts include intralesional wart injection with agents such as vitamin D, measles, mumps, and rubella (MMR) vaccine antigen, Bacillus...
BACKGROUND
New treatment options for warts include intralesional wart injection with agents such as vitamin D, measles, mumps, and rubella (MMR) vaccine antigen, Bacillus Calmette-Guerin (BCG) antigen, and candida antigen but there have been limited studies to compare their efficacies.
OBJECTIVE
The purpose of this systematic review is to compare the efficacy and safety of injectable agents used for the treatment of warts.
METHODS
A PubMed search included terms "intralesional wart therapy," "wart injection" and "verruca injection." Articles reviewed were published over 10 years.
RESULTS
A total of 43 articles were reviewed; 30 covered studies with more than 10 participants and 13 were case reports, case series, and reviews. In comparison studies intralesional agents have equal or superior efficacy (66%-94.9%) compared to first-line salicylic acid or cryotherapy (65.5-76.5%). One advantage of intralesional injections is the rate of complete resolution of distant warts.
LIMITATIONS
Each study varied in their agents, treatment interval, and treatment dose, making comparisons difficult.
CONCLUSIONS
Intralesional wart injections are safe, affordable, and efficacious treatments for warts. Physicians should consider intralesional injections for patients with refractory warts, multiple warts, or warts in sensitive areas.
Topics: Aminolevulinic Acid; Anti-Bacterial Agents; Antiviral Agents; BCG Vaccine; Bacterial Vaccines; Humans; Injections, Intralesional; Interferon-alpha; Mycobacterium; Tuberculin; Vitamin D; Warts
PubMed: 32609439
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2022With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory... (Review)
Review
BACKGROUND
With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID-19) is required.
OBJECTIVES
To assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in-hospital) with any severity of COVID-19, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID-19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid-19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials from this source until the first week of April 2022.
SELECTION CRITERIA
We included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID-19. We used the WHO definitions of illness severity for COVID-19.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all-cause mortality (up to day 28), all-cause mortality (up to day 60), improvement in clinical status: alive and without need for in-hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections.
MAIN RESULTS
We included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non-COVID-19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non-pharmaceutical procedures. At study entry, about 65% of participants required low-flow oxygen, about 23% required high-flow oxygen or non-invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending. Individuals with moderate to severe disease Four studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants). Systemic JAK inhibitors probably decrease all-cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate-certainty evidence), and decrease all-cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high-certainty evidence). Systemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate-certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate-certainty evidence). Systemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate-certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate-certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low-certainty evidence). Subgroup analysis by severity of COVID-19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors. Individuals with asymptomatic or mild disease We did not identify any trial for this population.
AUTHORS' CONCLUSIONS
In hospitalised individuals with moderate to severe COVID-19, moderate-certainty evidence shows that systemic JAK inhibitors probably decrease all-cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate-certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate-certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low-certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID-19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors. Currently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non-hospitalised individuals).
Topics: Antiviral Agents; Coinfection; Humans; Janus Kinase Inhibitors; Oxygen; Randomized Controlled Trials as Topic; SARS-CoV-2; United States; COVID-19 Drug Treatment
PubMed: 35695334
DOI: 10.1002/14651858.CD015209 -
Intervirology 2015We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6... (Meta-Analysis)
Meta-Analysis Review
Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis.
OBJECTIVES
We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).
METHODS
Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11.
RESULTS
Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates.
CONCLUSIONS
Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.
Topics: Antiviral Agents; Coinfection; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Immunologic Factors; Interferon-alpha; Polyethylene Glycols; Polymorphism, Genetic; Ribavirin; Treatment Outcome
PubMed: 27010195
DOI: 10.1159/000444366 -
BioMed Research International 2022A rare type of pneumonia later on referred to as COVID-19 was reported in China in December 2019. Investigations revealed that this disease is caused by a coronavirus... (Review)
Review
A rare type of pneumonia later on referred to as COVID-19 was reported in China in December 2019. Investigations revealed that this disease is caused by a coronavirus previously identified as SARS-CoV-2, and since then, it has become a global pandemic with new strains emerging rapidly as a result of genetic mutations. Various therapeutic options are being explored in order to eradicate this pandemic even though approved vaccine candidates are being currently rolled out globally. Most medicinal plant extracts have astonishing properties, and they can therefore be used in the biosynthesis of effective antiviral nanoparticles. In this systematic review, we aimed to highlight the specific attributes that make (neem plant) a suitable candidate for the biosynthesis of anti-SARS-CoV-2 nanoparticles. A systematic investigation was therefore carried out in PubMed, Scopus, Web of Science, and AJOL databases with the keywords "Nanoparticles," "Biosynthesis," "Antivirals," "SARS-CoV-2," and "." 1216 articles were retrieved by the 21 of February 2022, but we screened studies that reported data on biomedical and antimicrobial assessment of extracts. We also screened studies that were reporting nanoparticles possessing antiviral properties against SARS-C0V-2, narrowing our results to 98 reports. Herein, the SARS-CoV-2 viral structure is briefly discussed with nanoparticles of biomedical importance in the design of SARS-CoV-2 antivirals. Most importantly, we focused on the biomedical and antiviral properties of extracts that could be of importance in the design of potential anti-SARS-CoV-2 nanoformulations.
Topics: Antiviral Agents; Azadirachta; Nanoparticles; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36158879
DOI: 10.1155/2022/5714035 -
Frontiers in Endocrinology 2022To perform a systematic review and meta-analysis of interferon and endocrine side effects, including their incidence, evaluation, and management. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To perform a systematic review and meta-analysis of interferon and endocrine side effects, including their incidence, evaluation, and management.
METHODS
PubMed was searched through March 7th, 2021, by 2 authors independently (LH Wang and H Zhao). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. Stata 16.0 (StataCorp LLC, 16.0) was the main statistical software for meta-analysis. The weighted incidence and risk ratio were estimated for primary thyroid disease and diabetes mellitus.
RESULTS
A total of 108 studies involving 46265 patients were included. Hypothyroidism was the most common thyroid disorder, followed by hyperthyroidism. IFN α+RBV treated patients experienced hypothyroidism in 7.8% (95%CI, 5.9-9.9), which was higher than IFN α (5.2%; 95%CI, 3.7-6.8) and IFN β (7.0%; 95%CI, 0.06-23.92). IFN α+RBV treated patients experienced hyperthyroidism in 5.0% (95%CI, 3.6-6.5), which was higher than IFN α (3.5%; 95%CI, 2.5-4.8) and IFN β (3.4%; 95%CI, 0.9-7.5). The summary estimated incidence of painless thyroiditis was 5.8% (95%CI, 2.8-9.8) for IFN α, and 3.5% (95%CI,1.9-5.5) for IFN α+RBV. The summary estimated incidence of diabetes was 1.4% (95%CI, 0.3-3.1) for IFN, 0.55% (95%CI, 0.05-1.57) for IFN α, 3.3% (95%CI,1.1-6.6) for IFN α+RBV.
CONCLUSIONS
Our meta-analysis shows a high incidence of endocrine adverse events provoked by IFN, further reinforced by combined RBV treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022334131.
Topics: Antiviral Agents; Humans; Hyperthyroidism; Hypothyroidism; Interferon-alpha; Prospective Studies; Retrospective Studies; Thyroid Diseases
PubMed: 35992107
DOI: 10.3389/fendo.2022.949003 -
Journal of the International AIDS... 2016Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission.
METHODS
We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I(2) statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results.
RESULTS AND DISCUSSION
We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin.
CONCLUSIONS
This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control.
Topics: Antiviral Agents; Coinfection; HIV Infections; Hepacivirus; Hepatitis C; Humans; Viral Load
PubMed: 27649908
DOI: 10.7448/IAS.19.1.20944 -
BMJ (Clinical Research Ed.) Sep 2021To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).
STUDY SELECTION
Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.
METHODS
After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.
RESULTS
As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.
CONCLUSION
In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol established a priori is included as a data supplement.
FUNDING
This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antiviral Agents; Bayes Theorem; COVID-19; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Humans; Immunization, Passive; Network Meta-Analysis; SARS-CoV-2; Treatment Outcome; COVID-19 Serotherapy
PubMed: 34556486
DOI: 10.1136/bmj.n2231 -
Leukemia Jun 2021Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% [51.5%-66.1%]) and 76.7% (67.4-84.0%; CHR: 48.5% [37.8-59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
Topics: Antiviral Agents; Humans; Interferon-alpha; Polycythemia Vera; Thrombocythemia, Essential
PubMed: 32868875
DOI: 10.1038/s41375-020-01020-4 -
Medicine Mar 2016All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However,... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Network Meta-Analysis of Randomized Controlled Trials: Comparative Effectiveness and Safety of Direct-Acting Antiviral Agents for Treatment-Naive Hepatitis C Genotype 1.
All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However, the optimum regimen remains inconclusive. We aim to compare interventions in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks after the end of treatment and adverse effects (AEs) (fatigue, headache, nausea, insomnia). PubMed, Embase, and the Cochrane Library were searched for RCTs until July 31, 2015. We estimated odds ratios (ORs) between treatments on clinical outcomes. Twenty-two eligible RCTs were included. Compared with peginterferon-ribavirin (PR), daclatasvir plus PR (OR 8.90, P < 0.001), faldaprevir plus PR (OR 3.72, P < 0.001), simeprevir plus PR (OR 3.59, P < 0.001), sofosbuvir plus PR (OR 4.69, P < 0.001) yield a significant effect in improving SVR12. Consistently, simeprevir plus PR (OR 3.49, P < 0.001), sofosbuvir plus PR (OR 4.51, P < 0.001), daclatasvir plus PR (OR 4.77, P < 0.001) also improved the rates of SVR24 significantly compared with PR. With respect to AEs, compared with PR, ledipasvir plus sofosbuvir plus PR (OR 2.13, P < 0.001) confer a significant AE in nausea, whereas daclatasvir plus PR (OR 0.20, P < 0.001 and OR 0.18, P < 0.001, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR. Daclatasvir plus PR was the most effective in SVR12 and SVR24, but caused an increased AEs profile (headache and insomnia). Combined ledipasvir with sofosbuvir or combination of PR was associated with higher incidence of fatigue and nausea.
Topics: Antiviral Agents; Comparative Effectiveness Research; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26945424
DOI: 10.1097/MD.0000000000003004