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Liver International : Official Journal... Mar 2024We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS
We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS
A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS
All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
PROSPERO RECORD
CRD42020146752.
Topics: Adult; Child; Adolescent; Humans; Child, Preschool; Sofosbuvir; Hepatitis C, Chronic; Antiviral Agents; Hepatitis C; Sustained Virologic Response; Hepacivirus; Drug Therapy, Combination; Genotype; Treatment Outcome; Carbamates; Imidazoles; Pyrrolidines; Valine
PubMed: 38293756
DOI: 10.1111/liv.15827 -
PloS One 2023Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in...
PURPOSE
Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients.
METHODS
The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool.
RESULTS
Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude.
CONCLUSION
There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.
Topics: Humans; Middle Aged; Cytidine Diphosphate Choline; Glaucoma, Open-Angle; Intraocular Pressure; Glaucoma; Retinal Ganglion Cells; Blindness
PubMed: 37768938
DOI: 10.1371/journal.pone.0291836 -
Viruses Jun 2023About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment... (Meta-Analysis)
Meta-Analysis Review
About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions ( < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.
Topics: Humans; Antiviral Agents; Sofosbuvir; Hepacivirus; Hepatitis C, Chronic; Ribavirin; Carcinoma, Hepatocellular; Sustained Virologic Response; Liver Neoplasms; Treatment Outcome; Hepatitis C; Genotype; Drug Therapy, Combination
PubMed: 37515176
DOI: 10.3390/v15071489 -
Advances in Rheumatology (London,... Jul 2023Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate...
BACKGROUND
Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults.
METHODS
Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively.
RESULTS
Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11-1.33), while reducing the BUA (MD - 66.05 µmol/L, 95% CI - 81.26 to - 50.84), 24-h UTP (MD - 0.83 g/24 h, 95% CI - 0.96 to - 0.70), BUN (MD - 0.90 mmol/L, 95% CI - 1.60 to - 0.20), IL-6 (MD - 6.99 ng/L, 95% CI - 13.22 to - 0.75), IL-8 (MD - 12.17 ng/L, 95% CI - 18.07 to - 6.27), TNF-α (MD - 8.50 ng/L, 95% CI - 15.50 to - 1.51), and adverse effects (RR 0.21, 95% CI 0.04-0.95).
CONCLUSION
Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.
Topics: Adult; Humans; Uric Acid; Nonprescription Drugs; Tumor Necrosis Factor-alpha; Capsules; Interleukin-8; Uridine Triphosphate; Gout; Randomized Controlled Trials as Topic
PubMed: 37464372
DOI: 10.1186/s42358-023-00310-6 -
Postgraduate Medical Journal Jul 2022This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19.
METHODS
We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs).
RESULTS
There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000.
CONCLUSION
SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery.
PROTOCOL REGISTRATION
PROSPERO: CRD42021247510.
Topics: Humans; COVID-19; GRADE Approach; Imidazoles; Sofosbuvir; COVID-19 Drug Treatment; Controlled Clinical Trials as Topic
PubMed: 37066509
DOI: 10.1136/postgradmedj-2021-140287 -
Nutrients Jan 2023Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance.
METHODS
We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models.
RESULTS
We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor.
DISCUSSION
Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.
Topics: Humans; Cytidine Diphosphate Choline; Alzheimer Disease; Cognitive Dysfunction; Cognition Disorders; Cognition
PubMed: 36678257
DOI: 10.3390/nu15020386 -
Annals of Medicine Dec 2023The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.
AIM
To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection.
METHODS
We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109).
RESULTS
Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration.
CONCLUSION
Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.
Topics: Humans; Sofosbuvir; Hepacivirus; Sustained Virologic Response; Antiviral Agents; Hepatitis C; Drug Therapy, Combination; Hyperglycemia; Genotype; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36655629
DOI: 10.1080/07853890.2023.2168745 -
Nefrologia 2021Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4-5 CKD.
STUDY AIMS AND DESIGN
We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4-5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.
RESULTS
Thirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I=99.8%) and 0.09 (95% CI, 0.05; 0.13, I=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, -0.01; 0.04, I=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.
CONCLUSIONS
SOF-based regimens appear safe and effective in patients with stage 4-5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.
Topics: Antiviral Agents; Creatinine; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; RNA; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 36165141
DOI: 10.1016/j.nefroe.2021.11.011 -
Expert Review of Clinical Pharmacology Aug 2022This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19.
RESEARCH DESIGN AND METHODS
PubMed, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 6, 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of SOF-DCV (study group) with alternative treatments (control group) in patients with COVID-19 were included.
RESULTS
A total of 9 RCTs were included. The all-cause mortality rate in the study group was 10.7% (96/898), which was lower than that in the control group (12.3%, 108/871). However, this difference was not statistically significant (odds ratio [OR] = 0.83; 95% CI, 0.62-1.12; = 49%). The overall clinical recovery rate was significantly higher in the study group than in the control group (OR = 2.34; 95% CI, 1.47-3.72; = 20%). Furthermore, the average length of hospital stay was shorter in the study group than in the control group (mean deviation = -1.84; 95% CI, -3.42 to -0.26, = 68%).
CONCLUSIONS
Although SOF-DCV did not confer a survival benefit in patients with COVID-19, it may increase a patient's odds of clinical recovery, and shorten the length of their hospital stay.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Humans; Imidazoles; Pyrrolidines; Randomized Controlled Trials as Topic; Sofosbuvir; Treatment Outcome; Valine; COVID-19 Drug Treatment
PubMed: 35852099
DOI: 10.1080/17512433.2022.2103539 -
Journal of Clinical Pharmacy and... Aug 2022Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regimens in several clinical scenarios, despite its well-known toxicities. The aim of our study is to systematically review and analyse the impact of adding RBV to SOF-based medication regimens on clinical outcomes among HCV patients.
METHODS
Included studies were randomized trials comparing the same SOF-based medication regimens with and without RBV in HCV patients and measuring serious adverse events (SAEs) and/or sustained virologic response at 12 weeks post-treatment (SVR-12). Two investigators independently searched PubMed and Cochrane Library through September 2021. The Cochrane Risk of Bias tool was used to assess trials quality. Clinical outcomes were analysed as risk ratios (RR) using a random effects model using R version 4.1.2.
RESULTS AND DISCUSSION
Our study included a total of 26 trials with 5058 HCV patients. Quality assessment showed moderate risk of bias for most trials. Upon adding RBV, there was no significant difference in SAEs (RR 1.07, 95% CI: 0.77-1.48, I = 10%), nor an impact on SVR-12 (RR 1.00, 95% CI: 0.98-1.01, I = 41%). There was no evidence of publication bias for either outcome. Subgroup analysis consistently showed lack of benefit among HCV subgroups. Additionally, NCT01826981 was identified as the main source of heterogeneity in the SVR-12 outcome.
WHAT IS NEW AND CONCLUSION
Our findings suggest nonsignificant differences in safety and efficacy between SOF-based medication regimens with and without RBV which should be considered in clinical practice.
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Ribavirin; Sofosbuvir; Treatment Outcome
PubMed: 35678040
DOI: 10.1111/jcpt.13698