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RMD Open Apr 2020To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised,... (Comparative Study)
Comparative Study
Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a...
OBJECTIVE
To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs).
METHODS
Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0-100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher's method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure.
RESULTS
With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher's method, respectively, were -12, -12 and -12 for baricitinib versus adalimumab and -7, -7 and -9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was -0.28, -0.28 and -0.30 for adalimumab and -0.23, -0.23 and -0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI.
CONCLUSIONS
Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Azetidines; Biological Products; Clinical Trials, Phase III as Topic; Disability Evaluation; Humans; Methotrexate; Network Meta-Analysis; Pain; Pain Measurement; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 32371431
DOI: 10.1136/rmdopen-2019-001131 -
The Cochrane Database of Systematic... Apr 2020This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology...
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs).
OBJECTIVES
To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective.
SEARCH METHODS
For the latest update we searched the following databases on 29 September 2019: Cochrane Epilepsy Group Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions.
SELECTION CRITERIA
We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group.
DATA COLLECTION AND ANALYSIS
Three review authors (JW, JG, YD) independently selected trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots.
MAIN RESULTS
We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One, three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Only five trials reported incidences of death. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low certainty for all reported outcomes due to methodological issues and variability of comparisons made in the trials.
AUTHORS' CONCLUSIONS
There is limited, low-certainly evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.
Topics: Anticonvulsants; Carbamazepine; Craniotomy; Humans; Isoxazoles; Levetiracetam; Phenobarbital; Phenytoin; Piracetam; Postoperative Complications; Randomized Controlled Trials as Topic; Seizures; Valproic Acid; Zonisamide
PubMed: 32343399
DOI: 10.1002/14651858.CD007286.pub5 -
Expert Review of Anti-infective Therapy Aug 2020Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and liver cancer. However, CHB can be treated with nucleos(t)ide analogues. We aimed to evaluate the effectiveness and safety of nucleos(t)ide analogues for the treatment of CHB patients.
METHODS
A systematic literature search was performed. Direct comparison meta-analyses and network meta-analysis (NMA) were carried out.
RESULTS
Thirty-six randomized controlled trials (RCTs) met inclusion criteria. Compared with placebo, the nucleos(t)ide analogues were all effective in HBeAg seroconversion, HBeAg loss, and achieving undetectable HBV DNA. Telbivudine was associated with higher HBeAg seroconversion compared with entecavir. For HBeAg loss rate and proportion of achieving undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent in the normalization of alanine aminotransferase (ALT). The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo.
CONCLUSION
The nucleos(t)ide analogues are all effective for HBeAg seroconversion, HBeAg loss, undetectable HBV DNA, and most are effective for ALT normalization in adults with CHB. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed.
Topics: Adult; Antiviral Agents; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Telbivudine; Tenofovir; Treatment Outcome
PubMed: 32329638
DOI: 10.1080/14787210.2020.1760843 -
Expert Review of Hematology May 2020: The traditional therapeutic modalities to manage SR-acute GVHD have focused on the inhibition of the alloreactive T-cell response, while in the setting of SR-chronic...
: The traditional therapeutic modalities to manage SR-acute GVHD have focused on the inhibition of the alloreactive T-cell response, while in the setting of SR-chronic GVHD the focus has been on a combination of T-cell and B-cell targeting strategies. However, new therapeutic modalities have shown promise. The purpose of this review is to summarize the current treatment landscape of SR-acute and chronic GVHD.: A systematic search of MEDLINE, EMBASE, and clinicaltrials.gov databases for published articles, abstracts, and clinical trials pertaining to available therapeutic modalities for SR-acute and SR-chronic GVHD was conducted. Also highlighted is a number of ongoing clinical trials in both SR-acute and SR-chronic GVHD with strategies targeting the JAK-1/2 pathway, the Treg:Tcon ratio, the immunomodulation mediated by mesenchymal stem cells, and the gut microbiome, among others. : Ruxolitinib has emerged as the preferred therapeutic modality for SR-acute GVHD, with alpha-1-antitrypsin and extracorporeal photophoresis (ECP) being reasonable alternatives. Ruxolitinib and Ibrutinib are among the preferred options for SR-chronic GVHD, with ECP being a viable alternative particularly if the skin is involved. A number of novel therapeutic modalities, including those enhancing the activity of regulatory T-cells have shown great promise in early phase trials of SR-chronic GVHD.
Topics: Acute Disease; Adenine; B-Lymphocytes; Chronic Disease; Graft vs Host Disease; Humans; Immunomodulation; Janus Kinase 1; Janus Kinase 2; Nitriles; Photopheresis; Piperidines; Pyrazoles; Pyrimidines; T-Lymphocytes, Regulatory; alpha 1-Antitrypsin
PubMed: 32249631
DOI: 10.1080/17474086.2020.1752175 -
Cancer May 2020The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy... (Comparative Study)
Comparative Study Meta-Analysis
Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis.
BACKGROUND
The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS.
METHODS
A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome.
RESULTS
A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant.
CONCLUSION
These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed.
Topics: Chemoradiotherapy; Deoxycytidine; Dose Fractionation, Radiation; Female; Humans; Kaplan-Meier Estimate; Male; Pancreatic Neoplasms; Prospective Studies; Radiosurgery; Retrospective Studies; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 32125712
DOI: 10.1002/cncr.32756 -
Expert Opinion on Pharmacotherapy May 2020In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the...
INTRODUCTION
In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)-signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).
AREAS COVERED
The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA.
EXPERT OPINION
In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.
Topics: Administration, Oral; Antirheumatic Agents; Arthritis, Psoriatic; Azetidines; Humans; Janus Kinases; Molecular Targeted Therapy; Phosphodiesterase 4 Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Thalidomide; Treatment Outcome
PubMed: 32057269
DOI: 10.1080/14656566.2020.1726317 -
Acta Diabetologica Jun 2020Observational studies and meta-analyses of randomized trials on dipeptidyl peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of malignancies with... (Meta-Analysis)
Meta-Analysis
AIMS
Observational studies and meta-analyses of randomized trials on dipeptidyl peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of malignancies with this class of drugs. Aim of the present meta-analysis is the assessment of the effect of DPP4i treatment on the incidence of different types of cancer, collecting all available evidence from randomized controlled trials.
METHODS
An extensive MEDLINE, EMBASE, and Cochrane database search for sitagliptin or vildagliptin or omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥ 24 weeks, and comparing of DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel-Haenszel odds ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes.
RESULTS
A total of 157 eligible trials were identified. DPP-4i were not associated with an increased risk of overall cancer (MH-OR 0.93 [0.86, 1.00]; p = 0.07), with no significant differences across individual molecules of the class. When compared with placebo/none, a lower risk of cancer with DPP-4i was observed in placebo-controlled trials (MH-OR 0.90 [0.82, 0.99], p = 0.030), whereas no significant differences have been detected with any other comparators. DPP-4i was associated with a significant reduction in colorectal cancer (MH-OR 0.70 [0.53, 0.94], p = 0.020).
CONCLUSIONS
Available data do not support the hypothesis of an association of DPP4i treatment with malignancies, with a possible beneficial effect for colon-rectal cancer.
Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Humans; Incidence; Neoplasms; Piperidines; Randomized Controlled Trials as Topic; Risk Factors; Sitagliptin Phosphate; Uracil; Vildagliptin
PubMed: 31955260
DOI: 10.1007/s00592-020-01479-8 -
International Journal of Colorectal... Feb 2020Direct randomized comparisons of regorafenib, TAS-102, and fruquintinib for treating metastatic colorectal cancer (mCRC) are lacking. Here, we evaluated the efficacy and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Direct randomized comparisons of regorafenib, TAS-102, and fruquintinib for treating metastatic colorectal cancer (mCRC) are lacking. Here, we evaluated the efficacy and safety of three agents by a systematic review and a network meta-analysis.
METHODS
We included phase III randomized controlled trials in the PubMed, Embase, and Scopus Cochrane databases and ClinicalTrials.gov registry from initiation until January 2019. Data from randomized controlled trials including overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were extracted. Direct meta-analysis and indirect meta-analysis using network meta-analysis were assessed.
RESULTS
Five trials comprising a total of 2586 patients were included. For efficacy analysis of OS, no statistically significant differences were observed between regorafenib and TAS-102 (HR 0.945, 95% CI [0.677, 1.320], P = 0.753), regorafenib and fruquintinib (HR 1.056, 95% CI [0.690, 1.621], P = 0.814), or TAS-102 and fruquintinib (HR 1.117, 95% CI [0.740, 1.685], P = 0.610). However, fruquintinib was superior in PFS compared with TAS-102 (HR 1.756, 95% CI [1.079, 2.857], P = 0.023). Regorafenib and TAS-102 appeared to have a similar effect on PFS (HR 0.907, 95% CI [0.611, 1.346], P = 0.641), as did regorafenib and fruquintinib (HR 1.592, 95% CI [0.968, 2.618], P = 0.067). None of the three agents were better in terms of all grade AEs or any grade of 3-5 AEs. However, subgroup analysis of AEs exhibited different toxicity profiles between the three drugs.
CONCLUSIONS
Indirect comparison suggested that the three agents had similar OS but that fruquintinib was superior in terms of PFS compared with that of TAS-102. These three agents had different toxicity profiles.
Topics: Antineoplastic Agents; Benzofurans; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Network Meta-Analysis; Phenylurea Compounds; Progression-Free Survival; Pyridines; Pyrrolidines; Quinazolines; Randomized Controlled Trials as Topic; Thymine; Time Factors; Trifluridine; Uracil
PubMed: 31848739
DOI: 10.1007/s00384-019-03477-x -
Microbial Pathogenesis Feb 2020Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND AIMS
Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients.
METHODS
All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I <50% for the test for heterogeneity. Publication bias was measured using Egger's test.
RESULTS
Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF).
CONCLUSION
Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.
Topics: Antibodies, Viral; Antiviral Agents; Drug Therapy, Combination; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Nucleosides; Randomized Controlled Trials as Topic; Seroconversion; Tenofovir; Treatment Outcome
PubMed: 31816402
DOI: 10.1016/j.micpath.2019.103912 -
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