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Experimental and Therapeutic Medicine Nov 2019Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin...
Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: 'HCV', 'hepatitis C', 'interferon', 'antiviral', 'treatment response' and 'insulin resistance'. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613-1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=-0.485; 95%CI=-0.713 to -0.256; P<0.001) and HOMA-β (difference in means=-15.448; 95%CI=-23.326 to -7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.
PubMed: 31602234
DOI: 10.3892/etm.2019.7995 -
PloS One 2016In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/OBJECTIVES
In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET.
METHODS
Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling.
RESULTS
Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13), or OS (RR 1.03; CI 0.77-1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04-1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82) and lower overall renal toxicity (RR 3.61; CI 1.24-10.51).
CONCLUSION
Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Fluorouracil; Humans; Interferons; Neoplasm Metastasis; Neuroendocrine Tumors; Randomized Controlled Trials as Topic; Somatostatin; Streptozocin; Treatment Outcome
PubMed: 27362760
DOI: 10.1371/journal.pone.0158140 -
Cancer Cell International Oct 2021Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about... (Review)
Review
BACKGROUND
Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection.
METHODS
Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15.
RESULTS
There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients.
CONCLUSIONS
The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
PubMed: 34627251
DOI: 10.1186/s12935-021-02230-1 -
Risk Management and Healthcare Policy 2021Vitamin D status is related to risks of influenza and respiratory tract infections. Vitamin D has direct antiviral effects primarily against enveloped viruses, and... (Review)
Review
INTRODUCTION
Vitamin D status is related to risks of influenza and respiratory tract infections. Vitamin D has direct antiviral effects primarily against enveloped viruses, and coronavirus is an enveloped virus. The 2019 coronavirus disease had a high mortality rate and impacted the whole population of the planet, with severe acute respiratory syndrome the principal cause of death. Vitamin D can adequately modulate and regulate the immune and oxidative response to infection with COVID-19. The goal of this systematic review was thus to summarize and decide if there were a link between vitamin D status and COVID-19 infection and prognosis.
METHODS
The protocol of this study is documented in the Prospero database and can be accessed with the protocol number CRD42020201283. PubMed and Google Scholar were used for a literature search from August 2020 to September 2020. We restricted the year of publication of reviewed articles to 2019-2020, and the selected language was English. Studies that used secondary data, feedback, or analysis of reviews were removed. To assess the standard of studies included, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used.
RESULTS
Of the nine studies reviewed, seven (77.8%) showed that COVID-19 infection, prognosis, and mortality were correlated with vitamin D status.
CONCLUSION
Most of the articles reviewed showed that blood vitamin D status can determine the risk of being infected with COVID-19, seriousness of COVID-19, and mortality from COVID-19. Therefore, maintaining appropriate levels of Vitamin D through supplementation or natural methods, eg, sunlight on the skin, is recommended for the public to be able to cope with the pandemic.
PubMed: 33447107
DOI: 10.2147/RMHP.S291584 -
Viruses Dec 2022Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA... (Review)
Review
Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.
Topics: Humans; Antiviral Agents; Influenza Vaccines; Defective Interfering Viruses; Defective Viruses; COVID-19; SARS-CoV-2; Orthomyxoviridae; Virus Replication
PubMed: 36560777
DOI: 10.3390/v14122773 -
Scientific Reports Mar 2023
Author Correction: Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies.
PubMed: 36890205
DOI: 10.1038/s41598-023-31052-6 -
PloS One 2011Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.
METHODOLOGY/PRINCIPAL FINDINGS
Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified.
CONCLUSIONS/SIGNIFICANCE
Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.
Topics: Health Policy; Humans; Immunocompromised Host; Influenza Vaccines; Placebos; Public Health
PubMed: 22216224
DOI: 10.1371/journal.pone.0029249 -
PloS One 2015The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs.
AIM
Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1.
METHODS
Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using 'pmeta' command in STATA program.
RESULTS
Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value.
CONCLUSIONS
Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions.
Topics: Antiviral Agents; Drug Therapy, Combination; Fatigue; Genotype; Hepacivirus; Hepatitis C; Humans; Odds Ratio; Publication Bias; Time Factors; Treatment Outcome; Viral Load
PubMed: 26720298
DOI: 10.1371/journal.pone.0145953 -
Journal of Clinical Microbiology Feb 2022Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of... (Meta-Analysis)
Meta-Analysis
Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of the intensive phase of treatment. These methods either have suboptimal accuracy or a long turnaround time. There is a need to identify alternative biomarkers to monitor TB treatment response. We conducted a systematic review of active pulmonary TB treatment monitoring biomarkers. We screened 9,739 articles published between 1 January 2008 and 31 December 2020, of which 77 met the inclusion criteria. When studies quantitatively reported biomarker levels, we meta-analyzed the average fold change in biomarkers from pretreatment to week 8 of treatment. We also performed a meta-analysis pooling the fold change since the previous time point collected. A total of 81 biomarkers were identified from 77 studies. Overall, these studies exhibited extensive heterogeneity with regard to TB treatment monitoring study design and data reporting. Among the biomarkers identified, C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) had sufficient data to analyze fold changes. All four biomarker levels decreased during the first 8 weeks of treatment relative to baseline and relative to previous time points collected. Based on limited data available, CRP, IL-6, IP-10, and TNF-α have been identified as biomarkers that should be further explored in the context of TB treatment monitoring. The extensive heterogeneity in TB treatment monitoring study design and reporting is a major barrier to evaluating the performance of novel biomarkers and tools for this use case. Guidance for designing and reporting treatment monitoring studies is urgently needed.
Topics: Adult; Biomarkers; C-Reactive Protein; Humans; Interferon-gamma; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha
PubMed: 34911364
DOI: 10.1128/JCM.01859-21 -
Health Technology Assessment... May 2016Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.
OBJECTIVES
To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza.
METHODS
We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.
RESULTS
Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).
CONCLUSIONS
Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002245.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Antiviral Agents; Asthma; Child; Dose-Response Relationship, Drug; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Neuraminidase; Oseltamivir; Randomized Controlled Trials as Topic; Zanamivir
PubMed: 27246259
DOI: 10.3310/hta20420