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Measles is a highly contagious but vaccine-preventable airborne-transmitted viral infection of which there has been a recent resurgence of cases worldwide over the past year, including in countries such as the UK, which had previously successfully achieved endemic measles elimination through vaccination programmes. Measles is typically a self-limiting illness, but can rarely cause severe, life-threatening disease, particularly when complicated by respiratory or neurological involvement. These severe complications are not typically seen in the absence of immunosuppression. We describe a rare case of severe measles with pneumonitis in an immunocompetent adult necessitating admission to an intensive care unit (ICU).

Reproductive toxicity is one of the major concerns in drug development. Thus, we have developed its screening system using Caenorhabditis elegans, which has a life cycle of three days and similar coding genes as humans. Antiviral nucleoside analogs used for acute infections are known to cause reproductive toxicity, contraindicated for pregnant women, and are used for comparing their reproductive toxicity in C. elegans and experimental animals. None of the drug treatments affected the number of offspring and the concentrations without toxicity to nematodes were consistent with no cytotoxicity or toxicity in experimental animals or humans. Favipiravir, ribavirin, molnupiravir (NHC), acyclovir, ganciclovir, zidovudine, and thalidomide significantly increased the incidence of arrested embryos but amenamevir, letermovir, and guanosine did not. RNA-dependent RNA polymerase (RdRp) inhibitors, in the order of favipiravir, ribavirin, and NHC increased the incidence of arrested embryos, possibly due to the specificity of favipiravir for RdRp and less cytotoxicity. RdRp inhibitors would impair RNA interference through RdRp expressed by telomerase reverse transcriptase during embryogenesis and cause embryo-fetal toxicity. The incidence of arrested embryos may be affected by differences in the substrate specificity of DNA polymerases and metabolism between C. elegans, animals, and humans. The concordance between the results of the screening system for reproductive toxicity of antivirals in C. elegans and those in experimental animals based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, reproductive toxicology confirms its appropriateness as a screening system for reproductive toxicity. Favipiravir and zidovudine were the least toxic to C. elegans among the antiviral drugs examined.

Background: Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. Rationale: In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. Results: The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. Conclusion: This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

During the COVID-19 pandemic, the extensive use of ribavirin (RBV) raised concerns about its environmental residues and associated risks, necessitating remedial actions. This study investigates the degradation efficiency, mechanism, and biotoxicity of RBV using ferrous (Fe2+) activated persulfate (PS) advanced oxidation technology (Fe2+/PS oxidation). Experiments conducted under various conditions revealed that at pH = 3, PS concentration of 4 mM, PS/Fe2+ molar ratio of 2:1, and citric acid of 0.5 mM with Fe2+ added twice, the degradation rate of RBV reached 98.70 %. The degradation process of RBV by Fe2+/PS from 0 to 5 mins followed a first-order reaction kinetics model. The presence of halide ions (Cl-, Br-, I-) was found to inhibit the degradation efficiency. The active species involved were identified as SO4-·, ·OH, 1O2, and FeO2+, with SO4-· and ·OH being the most significant. Moreover, the products of ribavirin were determined and their degradation pathways were proposed. Dehydration, deamidation, C-N bond breaking and hydroxylation were the major pathways. Additionally, toxicity assessment showed that Fe2+/PS oxidation reduced the inhibition rate of bioluminescence in Vibrio fischeri from 31.58 % to 3.88 %, effectively controlling RBV toxicity during the reaction. This study provides insights into managing water environmental risks associated with pharmaceutical residues in the post-pandemic era.

Objectives: Liberia is endemic to Lassa fever (LF) and has the largest reported per capita incidence of LF patients in the West African region. Cases of the disease increased unprecedentedly in 2019 and 2020, characterized by a geographical drift in epidemiology and seasonal variation of occurrence. This study aims to describe the epidemiological and clinical characteristics of LF in Liberia from 2019 to 2020. Methods: A retrospective study was conducted on cases of LF confirmed at the National Public Health Reference Laboratory from January 2019 to December 2020. Medical records were reviewed, and epidemiological and clinical data were collected in an organized manner. Descriptive and inferential statistics were carried out using Epi Info (version 7.2.5.0). Results: A total of 382 suspected LF cases were reported, of which 103 were laboratory-confirmed, yielding a case positivity rate of 27% (103/382). The median age of the LF cases was 20 (IQR: 9–30). Children younger than 18 years accounted for 40.8% (42/103) of the cases and healthcare workers’ cases constituted 7.7% of the cases. Bong, Nimba, and Grand Bass accounted for 87.4% of the cases with cases in new counties like Lofa, Margibi, and Grand Kru. Hemorrhage (aOR:10.2; 95% CI: 3.11–33.81), patients who did not receive ribavirin (aOR: 4.4; 95% CI: 1.12–17.57, P = 0.034), and patients aged 40 years or older (aOR: 6.2; 95% CI: 1.19–32.53, P = 0.049) were associated with LF mortality. Conclusion: The LF cases in 2019 and 2020 had a high case fatality rate and spread to new counties that had not previously reported LF. The disease occurred during most of the rainy season instead of the usual dry season. There is an urgent need to lower morbidity and mortality, improve early presentation to the hospital, and early initiation of appropriate medical care.

In immunocompromised individuals persisting viremia frequently leads to a chronic hepatitis E virus (HEV) infection. Zoonotic transmission of HEV from pigs and wild boar to humans is proven and sporadic infections with rabbit HEV (raHEV) have recently been reported. Here, the molecular characterisation of a raHEV strain isolated from an immunocompromised, chronically HEV-infected, heart-transplanted patient is described. After successful ribavirin (RBV) treatment of a HEV infection in 2019, the patient was again tested HEV positive in 2021 and received a second RBV therapy cycle. Full-length HEV genome amplification and next generation sequencing was performed on a plasma sample taken between first and second cycle of RBV therapy and a stool sample taken two months after starting the second cycle. The sequence of plasma (raHEV-83) and stool (raHEV-99) derived virus showed the highest nucleotide sequence identity to a Chinese raHEV and a phylogenetic relationship to a raHEV strain isolated from a French patient. Furthermore, sequence analysis revealed the presence of RBV-associated substitutions V1479I and G1634K in the HEV sequences from plasma and additionally K1398R from stool. The results underline the role of rabbits as putative sources of HEV infection and emphasize the need of a one health concept for a better understanding of HEV epidemiology and to develop tools for prevention and control of HEV infection.

Antiviral drugs have garnered considerable attention, particularly in the global battle against the COVID-19 pandemic, amid heightened concerns regarding environmentally acquired antiviral resistance. A comprehensive understanding of their transport in subsurface environments is imperative for accurately predicting their environmental fate and risks. This study investigated the mobility and retention characteristics of six COVID-19 antiviral drugs in saturated quartz sand columns. Results showed that the mobility of the drugs was primarily contingent on their hydrophobicity, with ribavirin and favipiravir exhibiting the highest transportability, while arbidol displaying the greatest retention. The transport characteristics of ribavirin and favipiravir remained largely unaffected by pH, whereas the retention of the other four antivirals remained consistently minimal under alkaline conditions. Elevating ionic strength marginally facilitated the transport of these antivirals, while the presence of Ca 2+ notably enhanced their retention in quartz sand compared to Na + . Ribavirin and remdesivir warrant particular attention due to their relatively high transportability and propensity for environmentally acquired antiviral resistance. These findings contribute to an enhanced understanding of the leachate potential and transport of COVID-19-related antivirals in sandy porous media, furnishing fundamental data for predicting their environmental fate and associated risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

α-Synuclein (α-syn) is an intrinsically disordered protein, linked genetically and neuropathologically to Parkinson's disease where this protein aggregates within the brain. Hence, identifying compounds capable of impeding α-syn aggregation puts forward a promising approach for the development of disease-modifying therapies. Herein, we investigated the efficacy of Ribavirin, an FDA-approved compound, in curtailing α-syn amyloid transformation, employing an array of bioinformatic tools and systematic analysis using biophysical techniques. Ribavirin shows a dose dependent anti-aggregation propensity where it effectively subdued the formation of mature fibrillar aggregates of α-syn, where even at the lowest concentration there was a 69 % reduction in the ThT maxima. Ribavirin averts the formation of mature fibrillar aggregates by interacting with the NAC domain of α-syn. Ribavirin redirects the amyloid transformation of α-syn by emanating aggregates of lower order with reduced cross β-sheet signature and revokes the formation of on-pathway amyloids. Collectively, our study puts forward the novel potency of Ribavirin as a promising molecule for therapeutic intervention in Parkinson's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial or personal interests that could appear to have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The Human Respiratory Syncytial Virus (RSV) is the leading cause of acute respiratory infections in children. Currently, no safe, effective, or feasible option for pharmacological management of RSV exists. Hence, plant-derived natural compounds have been explored as promising antiviral agents. Mangifera indica is a globally distributed plant with reported anti-inflammatory, cardioprotective, and antiviral activities. Our study investigated the antiviral potential of a novel pectin from M. indica peels (PMi) and its chemically sulfated derivative (PSMi) against RSV in HEp-2 cells. The compounds were characterized using Fourier-transform infrared spectroscopy and nuclear magnetic resonance (NMR). NMR analysis revealed the presence of ester and carboxylic acid groups in PMi, and sulfation resulted in a sulfation degree of 0.5. PMi and PSMi showed no cytotoxic effects even at concentrations as high as 2000 μg/mL. PSMi completely inhibited RSV infectivity (100-1.56 μg/mL, 50 % inhibitory concentration of viral infectivity = 0.77 ± 0.11 μg/mL). The mechanism of action was investigated using the 50 % tissue culture infectious dose assay . PSMi displayed virucidal activity at concentrations from 100 to 6.25 μg/mL, and a significant reduction in viral infection was observed at all treatment times. Overall, PSMi is antiviral, cell-safe, and exhibits promising potential as an RSV treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule., Competing Interests: Declaration of competing interest The authors of the manuscript “Computational and Biological Approaches in Repurposing Ribavirin for Lung Cancer Treatment: Unveiling Antitumorigenic Strategies”, submitted to the journal “Life Sciences”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: HEV variants such as swine genotypes within Paslahepevirus species balayani (HEV-A) and rat HEV (Rocahepevirus ratti; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised rat model of chronic hepatitis E infection. Methods: In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant recipients. Rats were challenged with human- and rat-derived HEV-C1 strains or a human-derived HEV-A strain. Viral load, liver function, liver histology, humoural, and cellular immune responses were monitored. Results: A high-dose (HD) immunosuppressive regimen consistently prolonged human- and rat-derived HEV-C1 infection in rats (up to 12 weeks post infection) compared with transient infections in low-dose (LD) immunosuppressant-treated and immunocompetent (IC) rats. Mean HEV-C1 viral loads in stool, serum, and liver tissue were higher in HD regimen-treated rats than in LD or IC rats (p

Objectives: The aim of this study was to evaluate the efficacy and safety of sofosbuvir/ledipasvir ± ribavirin in Malagasy patients with hepatitis C virus genotypes 1 and 2, in real conditions. Patients and methods: This was a retrospective monocentric clinical study, carried out over a period of 3 years from March 1, 2017 to February 28, 2020, in a hospital hepato-gastroenterology department. Results: In total, 26 patients (M/F: 11/15) with hepatitis C virus genotype 1 (n = 13) or genotype 2 (n = 13), were treated with sofosbuvir/ledipasvir without (n = 21) or with (n = 5) ribavirin for 12 weeks. The mean age was 61.38 ± 7.09 years. Seventeen patients (65.4%) had cirrhosis. The overall sustained virological response was 96.2% (95% CI = 80.4–99.9%). There was no significant difference between the sustained virological responses of genotypes 1 and 2 (92.3% vs 100%; p = 0.31) or those of cirrhotic or non-cirrhotic patients (94.1% vs 100%; p = 0.46). A relapse was observed in one patient (5.9%) — cirrhotic and genotype 1b — under sofosbuvir/ledipasvir with ribavirin. Seven patients (26.9%) experienced mild adverse reactions, including asthenia (57.1%) and insomnia (42.9%). Conclusion: Treatment with sofosbuvir/ledipasvir ± ribavirin for infection with hepatitis C virus genotype 1 has been shown to be safe and effective, even in the presence of cirrhosis. The sofosbuvir/ledipasvir combination is a good option for genotype 2 non-cirrhotic patients.

COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose an international public health threat and thus far, has resulted in greater than 6.4 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast-spreading COVID-19 variants that may elude vaccine efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential enzyme of viral replication and transcription machinery complex. Therefore, the RdRp is an attractive target for the development of effective anti-COVID-19 therapeutics. In this study, we developed a cell-based assay to determine the enzymatic activity of SARS-CoV-2 RdRp through a luciferase reporter system. The SARS-CoV-2 RdRp reporter assay was validated using known inhibitors of RdRp polymerase, remdesivir along with other anti-virals including ribavirin, penciclovir, rhoifolin, 5′CT, and dasabuvir. Dasabuvir (an FDA-approved drug) exhibited promising RdRp inhibitory activity among these inhibitors. Anti-viral activity of dasabuvir was also tested on the replication of SARS-CoV-2 through infection of Vero E6 cells. Dasabuvir inhibited the replication of SARS-CoV-2, USA-WA1/2020 as well as B.1.617.2 (delta variant) in Vero E6 cells in a dose-dependent manner with EC50 values 9.47 μM and 10.48 μM, for USA-WA1/2020 and B.1.617.2 variants, respectively. Our results suggest that dasabuvir can be further evaluated as a therapeutic drug for COVID-19. Importantly, this system provides a robust, target-specific, and high-throughput screening compatible (z- and z’-factors of >0.5) platforms that will be a valuable tool for screening SARS-CoV-2 RdRp inhibitors.

Background: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Objective: To assess the efficacy and safety of ribavirin and interferon-α (RBV/IFN-α) therapy in COVID-19 patients. Methods: A multicenter, retrospective cohort study of COVID-19 patients admitted to 4 hospitals in Hubei Province, China, from 31 December 2019 to 31 March 2020. Patients were divided into 2 groups according to their exposure to RBV/IFN-α therapy within 48 h of admission. Mixed-effect Cox model and Logistic regression were used to explore the association between early treatments of RBV/IFN-α and primary outcomes. Results: Of 2037 patients included, 1281 received RBV/IFN-α (RBV, IFN-α or RBV combined with IFN-α) treatments and 756 received none of these treatments. In a mixed effect model, RBV/IFN-α therapy was not associated with progression from non-severe into severe type (adjusted hazard ratio (aHR) = 1.09, 95% CI: 0.88−1.36) or with reduction in 30-day mortality (aHR = 0.89, 95% CI: 0.61−1.30). However, it was associated with a higher probability of hospital stay >15 days (adjusted odds ratio (aOR) = 2.11, 95% CI: 1.68−2.64) compared with no RBV/IFN-α therapy. The propensity score-matched cohort and subgroup analysis displayed similar results. Conclusion: RBV/IFN-α therapy was not observed to improve clinical outcomes in COVID-19 patients suggesting that RBV/IFN-α therapy should be avoided in COVID-19 treatment.

Ribavirin, an antiretroviral agent targeting the hepatitis C virus, causes male reproductive toxicity. This study investigated the mechanism of ribavirin transport at the blood-testis barrier (BTB). In vivo mouse integration plot analysis after intravenous administration revealed that the net influx clearance of [ 3 H]ribavirin in the testis was 3.6-fold greater than that of [ 14 C]D-mannitol, a paracellular transport marker, implying transcellular transport of ribavirin across the BTB. Moreover, [ 3 H]ribavirin uptake by TM4 cells, mouse-derived Sertoli cells, was time- and concentration-dependent, with a K m value of 2.49 mM. S-[(4-nitrophenyl)methyl]-6-thioinosine, an inhibitor of Na + -independent equilibrative nucleoside transporters (ENTs), strongly inhibited the [ 3 H]ribavirin uptake by TM4 cells at 100 µM. Compared to the uptake of [ 3 H]adenosine, a typical endogenous nucleoside, [ 3 H]ribavirin uptake was relatively similar to ENT2 transport. [ 3 H]Ribavirin uptake was also observed in mouse ENT2-expressing Xenopus laevis oocytes, and gene silencing via the transfection of ENT2 small interfering RNA significantly reduced the [ 3 H]ribavirin transport into TM4 cells by 13%. Taken together, these results suggest that ENT2 partially contributes to ribavirin transport at the BTB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia. Methods: We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants. Results: We identified a novel association in the gene coding glycophorin C (rs6741425; OR:0.12, 95%CI:0.04–0.34, P = 2.94 × 10-6) that predicts protection against ribavirin-induced anemia. We also replicated the associations of ITPA and VDR genetic variants with the development of ribavirin-induced anemia (rs1127354; OR:0.13, 95%CI:0.04–0.41, P = 8.66 ×10-5; and rs1544410; OR:1.65, 95%CI:1.01–2.70, P = 0.0437). Conclusions: GYPC variation affecting erythrocyte membrane strength is important in predicting risk for developing ribavirin-induced anemia. ITPA and VDR genetic variants are also important predictors of this adverse reaction.

Introduction: A keloid is a type of benign fibrotic disease with similar features to malignancies, including anti-apoptosis, over-proliferation, and invasion. Epithelial-mesenchymal transition (EMT) is a crucial mechanism that regulates the metastatic behavior of tumors. Thus, identifying EMT biomarkers is paramount in comprehensively understanding keloid pathogenesis., Methods: To identify the differentially expressed genes (DEGs) GSE92566 dataset, with 3 normal skin and 4 keloid tissues, was downloaded from GEO databases to identify the differentially expressed genes (DEGs). Further, EMT-related genes were downloaded from dbEMT 2.0 databases and intersected with GSE92566 DEGs to identify EMT-related-DEGs (ERDEGs). Subsequently, the ERDEGs were used for GO, KEGG, gene set enrichment analysis (GSEA), protein-protein interaction (PPI), and miRNAs-mRNAs network analysis. To predict small molecules for EMT inhibition, the ERDEGs were imported to cMAP databases, whereas hub genes were imported to DGidb databases. Finally, we carried out qRT-PCR and in vitro experiments to validate our findings., Results: A total of 122 ERDEGs were identified, including 59 upregulated and 63 down-regulated genes. Moreover, enrichment analysis revealed that focal adhesion, AMPK signal pathway, Wnt signal pathway, and EMT biological process were significantly enriched. STRING databases and Cytoscape software were used to construct the PPI network and EMT-related hub genes. Further, 3 modules were explored from the PPI network using the Molecular Complex Detection (MCODE) plugin. In the Cytohubba plugin, 10 hub genes were explored, including FN1, EGF, SOX9, CDH2, PROM1, EPCAM, KRT19, ITGB1, CD24, and KRT18. These genes were then enriched for the focal adhesion pathway. We constructed a microRNA (miRNA)-mRNA network, which predicted hsa-miR-155-5p (8 edges), hsa-miR-124-3p (7 edges), hsa-miR-145-5p (5 edges), hsa-miR-20a-5p (5 edges) and hsa-let-7b-5p (4 edges) as the most connected miRNAs regulating EMT. Based on the ERDEGs and 10 hub genes mentioned above, ribavirin demonstrated high drug-targeting relevance. Subsequently, qRT-PCR confirmed that the expression of FN1, ITGB1, CDH2, and EPCAM corroborated with previous findings. qRT-PCR also showed that the expression levels of hsa-miR-124-3p and hsa-miR-145-5p were significantly lower in keloids and hsa-miR-155-5p was upregulated in keloids. Finally, by treating human keloid fibroblasts (HKFs) with ribavirin in vitro, we confirmed that ribavirin could inhibit HKFs proliferation and EMT., Conclusion: In summary, this work provides novel EMT biomarkers in keloids and predicts new small target molecules for keloid therapy. Our findings improve the understanding of keloid pathogenesis, providing new treatment options., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: This study aimed to investigate the effect of single nucleotide polymorphisms (SNPs) of genes involved in ribavirin (RBV) transport (SLC28A2 gene, ABCB1 gene and ABCB11 gene) on the clinical outcome and pharmacokinetics of ribavirin in HCV- 4 Egyptian patients. Method: 100 patients treated with sofosbuvir/daclatasvir and ribavirin for 12 weeks. The SNP genotyping was performed by real-time PCR using high resolution melting analysis. Ribavirin plasma trough concentrations were determined at week 4 of therapy using a liquid chromatography/tandem mass spectrometry (LC–MS/MS). For clinical outcomes, sustained virological response (SVR), liver function tests (ALT and AST), total bilirubin, albumin, serum creatinine, hemoglobin, leukocyte count, and platelet count were measured. Results: Concerning RBV pharmacokinetics, ABCB1 2677 G > T SNP and ABCB11 1331 T > C SNP were statistically associated with RBV Ctrough levels after 4 weeks of therapy. ABCB11 1331 T > C SNP revealed significant association with clinical outcomes (SVR). SLC28A2-146 A > T SNP has not showed any statistically significant association with RBV plasma levels or response. Conclusion: SNP genotyping for ABCB1 and ABCB11 genes can help in better personalized medicine for maximizing response for ribavirin as explored by the significant association between polymorphism in ABCB1 and ABCB11 genes and ribavirin pharmacokinetics and the significant association of ABCB11 1331 T > C SNP with clinical response.

Background and aim. Grazoprevir is an NS3/4A protease inhibitor (PI), while elbasvir is an NS5A inhibitor. We performed this meta-analysis to directly compare grazoprevir plus elbasvir and ribavirin regimen vs. grazoprevir and elbasvir without ribavirin in the treatment of hepatitis C virus genotype 1 infection and to precisely evaluate the efficacy of the latter regimen in cirrhotic, IL28 CC genotype patients and those coinfected with human immunodeficiency virus.Material and methods. A computer literature search of PubMed, Scopus, EBSCO, Embase, and Cochrane central was conducted. Studies were screened for eligibility. Sustained virologic response (SVR) rates were pooled using OpenMeta [Analyst] software for windows. A subgroup analysis was performed to stratify the treatment efficacy according to the different baseline characteristics of HCV patients.Results. Eight randomized controlled trials (n = 1,297 patients) were pooled in the final analysis. The overall SVR rate was 96.6% with 95% CI [95.5% to 98%]. For cirrhotic patients, the SVR rate was 95.7% with 95% CI [93.9% to 97.5%] and for non-cirrhotic patients, the SVR rate was 97% with 95% CI [95.9% to 98.4%]. Furthermore, the addition of ribavirin (RBV) to the treatment regimen did not significantly improve the SVR (RR 1.003, 95% CI [0.944 to 1.065]).The dual regimen was effective in patient populations with NS3 resistance-associated substitution (RAS). However, this regimen achieved lower SVR rates (< 90%) in patients with NS5A RAS.Conclusions. We conclude that the 12-week treatment regimen of the fixed dose combination of grazoprevir plus elbasvir achieved high SVR rates in patients with HCV genotype 1 infection. The addition of ribavirin to this regimen did not add a significant benefit.

Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. Methods: A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. Results: We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. Conclusion: In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.

Crimean-Congo hemorrhagic fever (CCHF) is a tick borne viral disease which can also be transmitted by direct contact with blood or tissue specimens of infected animals or humans. We present a fatal case of CCHF, who was diagnosed after death, and describe the post-exposure management plan for the health care workers (HCWs) involved in her care. In total of 52 HCWs were involved in the patient’s care and they were stratified into risk groups. Overall, 20 HCWs were grouped in high and intermediate risk groups, including the HCW with needle stick injury. High and intermediate risk groups were offered post exposure prophlaxis (PEP) with ribavirin. Fourteen of 20 HCWs started PEP, however 10 ceased after negative CCHF-PCR results. Negative CCHF-PCR results were reported for all HCWs at the 5th day of exposure. Side effects with PEP developed in 5 of HCWs and were mainly gastrointestinal complaints which reversed after drug discontinuation. All HCWs were followed for 14 days both clinically and with laboratory tests. None of the HCWs developed CCHF. PEP with ribavirin can be considered as a safe option in protection.

Background: The addition of ribavirin (RBV) to the combination treatment of Ledipasvir (LDV) and Sofosbuvir (SOF) remains controversial in the treatment of hepatitis C virus (HCV) infection. We performed a meta-analysis to assess the efficacy and safety of the LDV-SOF with and without RBV in treating HCV genotype 1 patients. Method: The electronical databases of PubMed Medline, EMBASE database, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov website with registered trials were searched. Eligible studies were randomized controlled trials (RCTs) and prospective cohort studies that assessed the efficacy and safety of LDV-SOF with or without RBV in patients with HCV genotype 1 (GT 1). Two reviewers independently screened studies, extracted data and assessed methodology quality. Review Manager 5.3 software was used to analyze the data. Results: Seven studies involving 2,626 patients with HCV GT 1 – some of whom had cirrhosis − were included in this meta-analysis. The addition of RBV to LDV- SOF regimen neither significantly improved sustained viral response at 12 weeks (SVR12) after the last dose of treatment (RR = 1.00, 95%CI 0.99-1.01, p = 0.99) nor decreased virologic breakthrough (RR = 1.01, 95%CI 0.14-7.19, p = 0.99) and relapse (RR = 1.36, 95% CI 0.81-2.29, p = 0.24). There was no significant difference in the incidence of discontinuation (RR = 0.61, 95%CI 0.25-1.53, p = 0.30) between LDV- SOF therapy and LDV- SOF plus RBV. LDV- SOF plus RBV therapy had significantly higher rate of the overall adverse events (RR = 0.88, 95%CI = 0.84- 0.92, p

Interferon-based simeprevir therapy showed high efficacy and tolerability in children with genotype 1 hepatitis C virus infection. While direct-acting antivirals (DAAs) therapy are undergoing study in children, this regimen is considered an available therapeutic option for selected patients in countries where DAAs have not yet been approved.

The target of the current study is to create a novel hybrid nanocomposite (Cs@Pyc.SOF) by combining the anti-hepatitis C virus (HCV) drug sofosbuvir with the nano antioxidant pycnogenol (Pyc) and nano biomolecules like chitosan nanoparticles (Cs NPs). The characterization procedure works to verify the creation of nanocomposite (NCP) using several different techniques. UV-Vis spectroscopy is used to measure SOF loading efficiency. The various concentrations of the SOF drug were used to determine the binding constant rate K b , which was found to be 7.35 ± 0.95 min -1 with an 83% loading efficiency. At pH 7.4, the release rate was 80.6% after two hours and 92% after 48 h, whereas at pH 6.8, it was 29% after two hours and 94% after 48 h. After 2 and 48 h, the release rate in water was 38% and 77%, respectively. . The SRB technique for fast screening is used for the cytotoxicity test, where the investigated composites show a safety status and high viability against the examined cell line. The cytotoxicity assay of the SOF hybrid materials has been identified with cell lines like mouse normal liver cells (BNL). So, Cs@Pyc.SOF was recommended as a substitute medication for the therapy of HCV, but the results need clinical studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background. Despite the introduction of direct antiviral agents, pegylated interferon remains the mainstay of treatment for chronic hepatitis C. However, pegylated interferon is associated with a high rate of severe adverse events and decreased quality of life. Specific interventions can improve adherence and effectiveness. We aimed to determine whether implementing a multidisciplinary approach improved outcomes in the treatment of chronic hepatitis C.Material and methods. We analyzed consecutive patients treated with pegylated interferon plus ribavirin between August 2001 and December 2011. We compared patients treated before and after the implementation of a multidisciplinary approach in 2007. We compared the baseline demographic and clinical characteristics and laboratory findings between groups, and used bivariate logistic regression models to detect factors involved in attaining a sustained virological response, calculating the odds ratios with their respective 95% confidence intervals. To evaluate the effect of the multidisciplinary team, we fitted a multivariate logistic regression model to compare the sustained virological response after adjusting for unbalanced variables and predictive factors.Results. We included 514 patients [228 (44.4%) in the pre-intervention cohort]. Age, viral genotype, previous treatment, aspartate transaminase, ferritin, and triglyceride were prognostic factors of sustained virological response. After adjusting for prognostic factors, sustained virological response was higher in the multidisciplinary cohort (58 vs. 48%, p = 0.038). Despite higher psychiatric comorbidity and age in the multidisciplinary cohort, we observed a trend toward a lower rate of treatment abandonment in this group (2.2 vs. 4.9%, p = 0.107).Conclusion. Multidisciplinary management of chronic hepatitis C improves outcomes.

Objectives: CD4+Foxp3+ regulatory T-cells (Treg) are known to accumulate under certain pathological conditions. This study was conducted to evaluate the characteristics of and dynamic changes in Treg cells in chronic hepatitis C (CHC) patients during antiviral therapy. Methods: One hundred and forty-five subjects were enrolled in this study, including 105 CHC patients and 40 healthy donors. The phenotypes and functions of Treg cells were analyzed by flow cytometry. Results: A significant elevation in Treg cells was observed in the peripheral blood of CHC patients compared with healthy donors. Interestingly, compared with non-suppressive Treg (non-Treg) and resting Treg (rTreg) cells, activated Treg (aTreg) cells expressed higher levels of ectonucleotidase, CD39, and CD73. After treatment with interferon alpha (IFN-α) and ribavirin (RBV) in vitro, the frequencies of total Treg cells and aTreg cells in peripheral blood mononuclear cells (PBMC), as well as the levels of transforming growth factor beta (TGF-β) secreted by aTreg and non-Treg cells, were significantly decreased. Importantly, it was found that levels of aTreg cells in patients with a sustained virological response (SVR) were lower than in relapsed patients, suggesting that a high frequency of aTreg cells might be associated with a poor clinical outcome in HCV infection. Conclusion: These results demonstrate a decreasing trend in aTreg cells, which express higher levels of CD39, CD73, and TGF-β, in SVR patients during antiviral therapy.

Objectives: To describe use of treatment for chronic hepatitis C virus (HCV) infection in HIV/HCV co-infected children and young people living in Europe and to evaluate treatment outcomes. Methods: HCV treatment data on children and young people aged >25 years with HIV/HCV co-infection were collected in a cohort collaboration of 11 European paediatric HIV cohorts. Factors associated with receipt of HCV treatment and with sustained virological response 24 weeks after treatment completion (SVR24) were explored. Results: Of 229 HIV/HCV co-infected patients, 22% had a history of AIDS and of 55 who were treated for HCV, 47 (85%) were receiving combined antiretroviral therapy. The overall HCV treatment rate was 24% (n=55) but it varied substantially between countries, with the highest rate being in Russia at 61% (30/49). Other factors associated with treatment receipt were older age [adjusted odds ratio (AOR) 5.24, 95% confidence interval (CI) 1.9–14.4, for 18–24-year-olds vs 11–17-year-olds, P=0.001] and advanced fibrosis (AOR 5.5, 95% CI 1.3–23.7; for ≥9.6 vs ≤7.2 kPa, P=0.02). Of 50 patients with known treatment outcomes, 50% attained SVR24. Of these, 16 (80%) had genotype (GT) 2,3 and 8 (29%) had GT 1,4 (P>0.001). After adjusting for genotype (GT 1,4 vs GT 2,3), females (P=0.003), patients with non-vertical HCV acquisition (P=0.002) and those with shorter duration of HCV (P=0.009) were more likely to have successful treatment outcomes. Conclusion: Only half of the HIV/HCV co-infected youth achieved an HCV cure. HCV treatment success appears to be lower in the context of HIV co-infection than in HCV mono-infection, underscoring the urgent need to speed up approvals of new direct-acting antiviral combinations in children.

Aim. Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia and a sustained viral response (sVR) during combination therapy.Material and methods. This study enrolled 62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment. At the occurrence of anemia (hemoglobin < 12 g/dL), the TVR-reduced group received 1500 mg TVR plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose (2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at 24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups.Results. No differences in the proportion of patients who became HCV RNA-negative were detected between the TVR-standard and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80% at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not statistically significant).Conclusions. TVR dose adjustment could prevent anemia progression without weakening the anti-viral effect during triple therapy in HCV-patients.

The first generation protease inhibitors has been the mainstay of hepatitis C treatment for the last couple of years, showing marked improvement in sustained virological response, but also increased side effects. Infection has emerged as a common complication of telaprevir and boceprevir in combination with peginterferon and ribavirin, usually caused by common pathogens. We present the case of a 65 years old man who developed a Mycobacterium abscessus pulmonary infection during treatment with telaprevir, peginterferon and ribavirin. The patient was successfully treated with amikacin, imipenem and chlarithro-mycin. The present case is relevant for increasing awareness for recognition of opportunistic infections and particularly nontuberculous mycobacterial infections in patients receiving triple therapy for chronic hepatitis C, especially in cirrhotic subjects who develop significant lymphopenia.

Ribavirin (RBV) that is not metabolically released into the environment can contaminate the environment and even make organisms resistant to it. Therefore, it is of great significance to establish a simple and effective method for adsorbing RBV in the environment. In this study, a novel biochar-based boronate affinity molecularly imprinted polymers (C@H@B-MIPs) were synthesized. This is the first time that shaddock peel biochar sphere was used as a carrier for specific recognition of RBV. The polymerization conditions were optimized and the binding properties of RBV were studied. Benefiting from the synergistic effect of boronate affinity and surface imprinting, the C@H@B-MIPs showed rapid equilibrium kinetics of 15 min, high adsorption capacity of 18.30 mg g -1 , and excellent reusability for RBV. The linear range was 0.05-100 mg L -1 , and the detection limit was 0.023 mg L -1 . This method was triumphant applied to the selective adsorption of RBV in food and water resources with recovery rates of 81.4-97.7%. This study provides a practical platform for the manufacture of efficient biomass-based adsorbents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial., Objectives: To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection., Data Sources: MEDLINE, Embase, and the Institute for Scientific Information Web of Science., Study Eligibility Criteria: Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection., Participants: Patients with HM/HSCT., Interventions: Ribavirin versus no ribavirin., Assessment of Risk of Bias: The risk of bias in non-randomized studies of exposure (ROBIN-E)., Methods of Data Synthesis: The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence., Results: One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I 2  = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I 2  = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I 2  = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I 2  = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I 2  = 71% (low certainty of evidence)., Conclusions: Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Crimean-Congo hemorrhagic fever virus (CCHFV) causes Crimean-Congo hemorrhagic fever (CCHF) in humans with high morbidity and mortality. Currently, there is neither an approved antiviral drug nor a vaccine against CCHFV. In this study, we describe a lethal model of CCHFV infection using a mouse-adapted strain of CCHFV (MA-CCHFV) in adult wild-type male mice. Infected mice developed high viral loads, tissue pathology, and inflammatory immune responses before ultimately succumbing to the infection. We used the model to evaluate the protective efficacy of nucleoside analogs monulpiravir, favipiravir, ribavirin, the antibiotic tigecycline and the corticosteroids dexamethasone and methylprednisolone against lethal CCHFV infection. Tigecycline, monulpiravir and the corticosteroids failed to protect mice from lethal MA-CCHFV infection. In contrast, favipiravir and ribavirin protected animals from clinical disease and death even when treatment was delayed. Despite demonstrating uniform protection, CCHFV RNA persisted in survivors treated with favipiravir and ribavirin. Nevertheless, the study demonstrated the anti-CCHFV efficacy of favipiravir and ribavirin in a model with intact innate immunity and establishes this model for continued development of CCHFV countermeasures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

A sensitive, simple and rapid square-wave adsorptive stripping voltammetric method was developed and validated for the determination of Ribavirin in pharmaceutical formulations. The proposed method was based on the electrochemical reduction of Ribavirin at a hanging mercury drop electrode in Britton Robinson buffer at pH 10. A well-defined peak was observed at 880 mV with 30 s of accumulation time and 50 mV of accumulation potential. Under these optimized conditions, the square-wave adsorptive stripping voltammetric peak current showed a linear correlation on drug concentration over the range of 1 × 10−10–2 × 10−7 mol L−1 with a correlation coefficient of 0.9995 for the proposed method. The detection and quantitation limits for this method were 2.02 × 10−10 and 6.80 × 10−10 mol L−1, respectively. The results obtained for intra-day and inter-day precision (as RSD %) were between 0.447% and 1.024%. This method was applied successfully for the determination of Ribavirin in its pharmaceutical dosage forms with mean recoveries of 99.68 ± 0.13 with RSD % of 0.81% and 99.20 ± 0.24 with RSD % of 0.49% for two concentrations 5 × 10−9 and 5 × 10−8 mol L−1, respectively for 200 mg capsules. The results obtained from the developed square-wave adsorptive stripping voltammetric method were compared with those obtained by the analytical method reported in the literature.

Background/Purpose. Hepatitis C (HCV) is a major cause of morbidity and mortality in haemophilia patients who received clotting factor concentrates before the availability of virus-inactivated factors in the mid-1980s. Recently, it has been suggested that anti-HCV treated patients, particularly those achieving a sustained virological response (SVR) have an improved outcome. We sought to examine the survival of treated and untreated HCV-infected haemophilia patients.Material and methods. We studied overall and liver-related survival of patients with haemophilia and other congenital bleeding disorders between 2000 and 2010. The outcome was compared in 3 sub-groups: HCV mono-infected (N = 127), HCV/HIV co-infected (N = 28), and patients with either HCV-antibodies negative or persistent HCV RNA-negative (referred to as non-infected) (N = 45). Sixty-two (40%) (HCV and HCV/HIV) patients underwent anti-HCV treatment with an SVR rate of 40.3%.Results. Overall and liver-related 10-year survival were: 82.1 and 89.3%, 95.3 and 99.2 and 100% for HCV/HIV co-infected, HCV mono-infected and non-infected haemophilia patients, respectively (p = 0.015 and 0.023 for comparisons of HCV/HIV vs. HCV; p = 0.003 for comparison of HCV/HIV and non-infected). One HCV mono-infected and 3 co-infected patients died of end-stage liver disease (2 underwent liver transplantation). There was no survival benefit from anti-HCV treatment or from attaining of an SVR. Only clinically suspected cirrhosis remained as an independent predictor of survival.Conclusion. The prognosis of haemophilia patients who acquired HCV/HIV co-infection is worse than that of HCV mono-infected or non-infected or haemophiliacs. This is mainly due to liver-related mortality. Anti-HCV treatment or SVR had no observable impact on survival rate.

Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with hemophilia. However, the efficacy and safety of pegylated interferon (PEG-IFN) plus ribavirin (RBV) for hemophilic patients with chronic HCV infection in Taiwan are still unknown. The aim of this study is to report the efficacy and safety of PEG-IFN plus RBV in a single center in Taiwan. Methods: In an open-label single-treatment one-arm cohort study, 12 hemophilic patients with elevated alanine aminotransferase level more than two times the upper limit of normal for more than 3 months received 180 μg/week of PEG-IFN-α-2a plus RBV 1000–1200 mg/day at a cut-off value of 75 kg. The duration of treatment was 48 weeks for patients with HCV Genotype 1/4 infection and 24 weeks for patients with HCV Genotype 2/3 infection. Efficacy of therapy was expressed as sustained virological response (SVR). Results: Eight patients achieved SVR (66.7%). The SVR rates were 57%, 100%, 100%, and 0% for patients with HCV Genotypes 1, 2, 3, and 4 infection, respectively. Adverse events (AEs) developed in 10 patients (83.3%). Severe thrombocytopenia developed in one patient. However, the patient did not suffer from severe bleeding. Conclusion: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-α-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well-conducted studies are still needed to verify the treatment efficacy and safety.

Background and aim. The treatment efficacy of peginterferon plus ribavirin for patients with HCV genotype 1 is inferior to that in patients with HCV genotype 2, but the efficacy among patients with mixed HCV genotype 1 + 2 is less clear. We compared the treatment outcome of peginterferon alpha-2b plus ribavirin among naïve chronic hepatitis C patients in Taiwan with HCV genotype 1 and 2, and mixed genotype 1 + 2.Material and methods. In this retrospective cohort study, 150 patients were treated with peginterferon alpha-2b once weekly, plus ribavirin, for 24 weeks. The endpoint was sustained virological response after receiving at least one dose of the study medication.Results. There were no differences in clinical characteristics among the 3 groups. There were significant differences in rapid virological response rate between patients with genotype 1 and genotype 2 (64.7 vs. 85.5%, respectively; p < 0.05) and a sustained virological response rate (55.9 vs. 83.6%, respectively; p = 0.001). The rapid virological response rate differed between the genotype 1 and mixed genotype 1 + 2 groups (64.7 vs. 85.2%, respectively; p < 0.05), but the sustained virological response rate was similar (55.9 vs. 74.1%; p = 0.101). Conclusions. Using peginterferon alpha-2b plus ribavirin for 24 weeks to treat patients with HCV genotype 1 + 2 achieved a 74.1% sustained virological response rate; the treatment efficacy was not inferior to patients with HCV genotype 1, but the percentage of liver cirrhosis in mixed genotype 1 + 2 group was higher to 22%, it is worth to be appropriately valued and studied.

Background & Aims: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial., Methods: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities., Results: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002)., Conclusion: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS., Gov Number: NCT04695769., Impact and Implications: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Respiratory syncytial virus (RSV) is a common agent of viral respiratory infections with significant morbidity and mortality in adults. The objective of this study was to determine risk factors for mortality and invasive mechanical ventilation and to describe the characteristics of patients who received ribavirin., Methods: A retrospective multicentre observational cohort study was conducted in Great Paris area hospitals, including patients hospitalised between 1 January 2015 and 31 December 2019 for documented RSV infection. Data were extracted from the Assistance Publique-Hôpitaux de Paris Health Data Warehouse. The primary endpoint was in-hospital mortality., Results: One thousand one hundred sixty-eight patients were hospitalised for RSV infection, including 288 (24.6%) patients who required intensive care unit (ICU) admission. The median (interquartile range) age of patients was 75 (63-85) years, and 54% (n = 631/1168) of them were women. In-hospital mortality was 6.6% (n = 77/1168) in the whole cohort and 12.8% (n = 37/288) in ICU patients. Factors associated with hospital mortality were age >85 years (adjusted odds ratio [aOR] = 6.29, 95% confidence interval [2.47-15.98]), acute respiratory failure (aOR = 2.83 [1.19-6.72]), non-invasive (aOR = 12.60 [1.41-112.36]), and invasive mechanical ventilation support (aOR = 30.13 [3.17-286.27]) and neutropenia (aOR = 13.19 [3.27-53.27]). Factors associated with invasive mechanical ventilation were chronic heart (aOR = 1.98 [1.20-3.26]) or respiratory failure (aOR = 2.83 [1.67-4.80]), and co-infection (aOR = 2.62 [1.60-4.30]). Patients who were treated with ribavirin were significantly younger than others (62 [55-69] vs. 75 [63-86] years; p < 0.001), more frequently males (n = 34/48 [70.8%] vs. n = 503/1120 [44.9%]; p 0.001), and almost exclusively immunocompromised (n = 46/48 [95.8%] vs. n = 299/1120 [26.7%]; p < 0.001)., Discussion: The mortality rate of patients hospitalised with RSV infections was 6.6%. Twenty-five per cent of the patients required ICU admission., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Increasing drug residues in aquatic environments have been caused by the abuse of antivirals since the global spread of the COVID-19 epidemic, whereas research on the photolytic mechanism, pathways and toxicity of these drugs is limited. The concentration of COVID-19 antivirals ribavirin in rivers has been reported to increase after the epidemic. Its photolytic behavior and environmental risk in actual waters such as wastewater treatment plant (WWTP) effluent, river water and lake water were first investigated in this study. Direct photolysis of ribavirin in these media was limited, but indirect photolysis was promoted in WWTP effluent and lake water by dissolved organic matter and NO 3 . Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C-N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge.- . Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C-N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction. Poor adherence to treatment for various chronic diseases is a frequent phenomenon. Current guidelines for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) recommend optimal adherence, since it has been suggested that poor adherence is associated with an increased risk of virological failure. We aimed to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV.Material and methods. A systematic review was conducted using the databases PubMed, Embase, Cochrane Library and Web of Knowledge. Search terms included “adherence” or “compliance” combined with “hepatitis B”, “hepatitis C” or “viral hepatitis”.Results. The final selection included 19 studies (13 HCV, 6 HBV). Large differences in patient numbers and adherence assessment methods were found between the various studies. For HCV mean adherence varied from 27 to 97%, whereas the proportion of patients with ≥ 80% adherence varied from 27 to 96%. Mean adherence reported in HBV studies ranged from 81 to 99%, with 66 to 92% of patients being 100% adherent. For both HCV and HBV studies, the highest adherence rates were reported in studies using self-report whereas lower adherence rates were reported in studies using pharmacy claims. Poor adherence to treatment was associated with an increased risk of virological failure.Conclusion. Non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. However, given the increased risk of virological failure in poorly adherent patients, clinicians should routinely address adherence issues in all patients treated for chronic viral hepatitis.

Background and aim. The commonly accepted treatment for hepatitis C virus (HCV) infection, pegylated interferon alpha (PEG INF-alpha) and ribavirin, leads to 50–60% of sustained virological response (SVR). On the other hand, pentoxifylline (PTX) possesses antiviral and hepatoprotector properties. Aim. To investigate whether the addition of PTX to conventional hepatitis C treatment increases SVR.Material and methods. Seventy two patients of both genders were studied in a randomized fashion; the diagnosis of chronic HCV infection was made according to clinical and laboratory criteria and histopathologically classified according to METAVIR scoring system criteria. HCV viral load was tested by PCR, baseline, and after 6 months of treatment, as well as anti-HCV, anti-hepatitis B virus, and anti-human immunodeficiency virus antibodies by enzyme-linked immunosorbent assay. During 48 weeks, control group patients were treated with PEG INF-alpha-2a plus ribavirin. PTX was administered to Experimental Group patients prior to the treatment.Results. Demographic data were similar in both groups. Experimental- and control-group subjects were at F2 and F3 states according to the METAVIR classification. The most common HCV genotypes were 1a and 1b (39% in the control group in each case, and 42% in the experimental group in each case). At the end of the study, hepatic enzymes and viral load decreased in both groups to similar values. SVR in the experimental group increased significantly (p < 0.05) when compared with standard therapy alone.Conclusion. Addition of PTX to conventional chronic hepatitis C treatment may increase the percentage of patients with SVR.

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.

Introduction. Porphyria cutanea tarda (PCT) is the most common type of porphyria. The strong association between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients undergoing peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis.Case presentation. A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 μg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT.