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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 -
PloS One 2021Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite... (Meta-Analysis)
Meta-Analysis
Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite adequate. The aim of this study was to evaluate the efficacy and safety of Sofosbuvir-based therapy without Ribavirin for all hepatitis C virus genotypes among patients with advanced CKD. We conducted an updated systematic literature search from the beginning of 2013 up to June 2020. Sustained virologic response (SVR) rate at 12 and/or 24 weeks after the end of treatment, and adverse events in HCV-infected patients with advanced CKD were pooled using random effects models. We included 27 published articles in our meta-analyses, totaling 1,464 HCV-infected patients with advanced CKD. We found a substantial heterogeneity based on the I2 index (P = 0.00, I2 = 56.1%). The pooled SVR rates at 12 and 24 weeks after the end of Sofosbuvir-based treatment were 97% (95% Confidence Interval: 95-99) and 95% (89-99) respectively. The pooled SVR12 rates were 98% (96-100) and 94% (90-97) in patients under 60 and over 60 years old respectively. The pooled incidence of severe adverse events was 0.11 (0.04-0.19). The pooled SVR12 rate after completion of the half dose regimen was as high as the full dose treatment but it was associated with less adverse events (0.06 versus 0.14). The pooled SVR12 rate was 98% (91-100) in cirrhotic patients and 100% (98-100) in non-cirrhotic patients. The endorsement of Sofosbuvir-based regimen can improve the treatment of hepatitis C virus infection in patients with advanced CKD.
Topics: Antiviral Agents; Hepatitis C; Hepatitis C, Chronic; Humans; Renal Insufficiency, Chronic; Sofosbuvir; Treatment Outcome
PubMed: 33566846
DOI: 10.1371/journal.pone.0246594 -
Journal of Hepatology Sep 2019The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models.
RESULTS
We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66).
CONCLUSION
Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates.
LAY SUMMARY
There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
Topics: 2-Naphthylamine; Adolescent; Adult; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cyclopropanes; Female; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Isoquinolines; Lactams, Macrocyclic; Liver Neoplasms; Liver Transplantation; Macrocyclic Compounds; Male; Proline; Ritonavir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Uracil; Valine; Young Adult
PubMed: 31096005
DOI: 10.1016/j.jhep.2019.04.017 -
BioMed Research International 2019Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to... (Meta-Analysis)
Meta-Analysis
Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to 4. Therefore, the efficacy and safety of DAAs for genotypes 5 and 6 need to be analysed. Studies were identified from Medline, Scopus, and CENTRAL and a Chinese database CNKI, from inception until Dec 4, 2018. Clinical trials were included if they enrolled patients with genotypes 5 and/or 6 infection, any type of second-generation DAAs was studied, and sustained virological response was assessed at the 12 week after treatment (SVR12) as outcome measure. Meta-analysis using statistical program was applied for pooling proportions if data were sufficient (i.e., at least 2 studies). Thirteen studies were included in the analysis. Four studies assessed the efficacy of four DAA regimens in genotype 5 patients, which were mainly sofosbuvir (SOF) plus pegylated-interferon/ribavirin (PR) or other DAAs, with SVR12 ranging from 94.4% to 100%. Twelve studies assessed the efficacy of seven DAA regimens among genotype 6 patients, but only two DAA regimens (i.e., SOF + PR and SOF/ledipasvir) had sufficient data for pooling. The pooled SVR12 rates (95% CI) were 99.6% (92.2 to 100) for SOF + PR and 99.2% (96.5 to 100) for SOF/ledipasvir. No treatment-related serious adverse event was reported, while the nonserious adverse events were comparable to other genotypes. In conclusion, DAAs are effective and may be safe for the treatment of chronic hepatitis C genotypes 5 and 6. However, our evidence is based on noncomparative studies; hence, further larger-scale randomized controlled trials in these genotypes are still required.
Topics: Antiviral Agents; Benzimidazoles; Databases, Factual; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Ribavirin; Sofosbuvir; Uridine Monophosphate
PubMed: 31815126
DOI: 10.1155/2019/2301291 -
Frontiers in Public Health 2022This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the...
OBJECTIVE
This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results.
METHODS
A literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles.
RESULTS
Of 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19-23).
CONCLUSION
EBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.
Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cost-Benefit Analysis; Cyclopropanes; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides
PubMed: 35646774
DOI: 10.3389/fpubh.2022.836986 -
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 -
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 Anti-infective Therapy Apr 2022Several randomized trials have evaluated the effects of sofosbuvir-based direct-acting antivirals on the clinical outcomes in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several randomized trials have evaluated the effects of sofosbuvir-based direct-acting antivirals on the clinical outcomes in patients with COVID-19.
METHODS
A systematic literature search with no language restrictions was performed on electronic databases and preprint repositories to identify eligible randomized trials published up to 8 July 2021. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest with the use of sofosbuvir combined with direct-acting antiviral agents relative to the nonuse of sofosbuvir-based direct-acting antiviral agents at 95% confidence intervals (CI).
RESULTS
The meta-analysis of 11 trials (n = 2,161) revealed statistically significant reduction in the odds of mortality (pooled odds ratio = 0.59; 95% confidence interval 0.36 to 0.99) but no statistically significant difference in the odds of development of composite endpoint of severe illness (pooled odds ratio = 0.79; 95% confidence interval 0.43 to 1.44) with the administration of sofosbuvir-based direct-acting antiviral agents among patients with COVID-19, relative to non-administration of sofosbuvir-based direct-acting antiviral agents.Subgroup analysis with seven trials involving sofosbuvir-daclatasvir revealed no significant mortality benefit (pooled odds ratio = 0.77; 95% confidence interval 0.48 to 1.22).
CONCLUSION
Sofosbuvir-based direct-acting antiviral agents have no protective effects against the development of severe illness in patients with COVID-19 with the current dosing regimen. Whether sofosbuvir-based direct-acting antiviral agents could offer mortality benefits would require further investigations.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepatitis C, Chronic; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Sofosbuvir; COVID-19 Drug Treatment
PubMed: 34719324
DOI: 10.1080/14787210.2022.2000861 -
BMC Infectious Diseases Sep 2021Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients.
METHODS
A systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL.
RESULTS
Six studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL.
CONCLUSIONS
For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Lipoproteins, LDL; Ribavirin; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 34548026
DOI: 10.1186/s12879-021-06657-9 -
Annals of Hepatology 2021Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness... (Meta-Analysis)
Meta-Analysis
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Topics: Antiviral Agents; Benzimidazoles; Carbamates; Drug Combinations; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Macrocyclic Compounds; Pyrrolidines; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides; Valine
PubMed: 33059055
DOI: 10.1016/j.aohep.2020.09.012