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ABSTRACT Background Methods and Results Conclusions Hepatitis C virus genotype 5 (HCV‐GT‐5) is found mainly in South Africa. In our area in central France, the prevalence of HCV‐GT‐5 is 14%.Here we evaluated sustained virological response at week 12 post‐treatment (SVR12) in 147 HCV‐GT‐5 patients from 14 French university hospitals (2014–2021) treated with direct‐acting antivirals (DAA) in real‐life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure.HCV‐GT‐5 patients treated with a DAA regimen had a 99% SVR12 in intention‐to‐treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real‐world HCV‐GT‐5 patients. [ABSTRACT FROM AUTHOR]

This study was conducted as a single‐site, open‐label, randomized, replicated crossover trial with 4 treatment periods. The aim was to evaluate the bioequivalence of a generic test drug containing velpatasvir and sofosbuvir compared to an established brand‐name medication in healthy White subjects under fasting conditions. Blood samples were collected at specified intervals up to 72 hours after dosing to measure the concentrations of velpatasvir and sofosbuvir using a certified high‐performance liquid chromatography with tandem mass spectrometry method. The bioequivalence of the 2 formulations was confirmed when statistical analysis showed that confidence intervals for the log‐transformed peak concentration and area under the concentration‐time curve from time 0 to the last quantifiable sample were within an acceptable range from 80% to 125%. Criteria for bioequivalence were met for both area under the concentration‐time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups. [ABSTRACT FROM AUTHOR]

Pig carboxylesterases (CESs) are recognized as enzymes that metabolize xenobiotics, and many drugs used in pig breeding that contain ester groups can be hydrolyzed by CESs. However, there are a limited number of publications focused on the molecular weight, inhibitor effects, and enzyme kinetics of porcine cytosolic carboxylesterase. This study presents the first investigation of the presence, kinetics, inhibition, and amino acid sequence of CES1, the major cytosolic CES isozyme in pig liver. The molecular weight of pig liver cytosolic CES1 was estimated to be approximately 179 kDa, and the amino acid sequence of the enzyme subunit was determined. The inhibition of CES1 by the antiviral drugs remdesivir and sofosbuvir was studied, and the IC50 values were determined. The results indicate that remdesivir and sofosbuvir can act as potent modulators of CES1. The inhibitors exhibited mixed‐type inhibition on pig liver cytosol CES1. It was found that the affinity of the remdesivir and sofosbuvir for free enzyme is greater than that for the enzyme‐substrate complex. A spectrofluorimetric method confirmed the inhibition findings, as the fluorescence intensity of remdesivir decreased upon interaction with the enzyme. [ABSTRACT FROM AUTHOR]

The importance of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) remains crucial in managing chronic HCV infection among patients who have experienced treatment failure and relapse after prior use of direct-acting antivirals (DAAs), as evidenced by high SVR12. However, limited real-world data exists on safety and efficacy. Therefore, the study's goal was to conduct a qualitative systematic review to assess SOF/VEL/VOX's effectiveness and safety. Thorough searches spanned PubMed, Embase, and Scopus, from 2015 to August 1st, 2023. The outcomes assessed were SVR12 and treatment-related adverse events (AEs). We identified and analyzed 12 studies in which SVR12 of the per-protocol (PP) population was 96.7% and of the intention-to-treat (ITT) population was 92.6% showing excellent efficacy of SOF/VEL/VOX. SVR12 rates notably differed among patients: those without GT3 infection (94.20%) and without cirrhosis (97.60%) experienced higher rates compared to patients having GT3 infection (87.40%) and cirrhotic patients (94.20%). Treatment-related AEs were also recorded. To summarize, our study presents evidence that SOF/VEL/VOX serves as an extremely safe and efficacious therapy for HCV-infected patients, previously treated with DAAs. [ABSTRACT FROM AUTHOR]

Background and purpose of the study: Sickle cell disease (SCD) patients are at a high risk of chronic liver disease (CLD) due to chronic viral hepatitis infection such as hepatitis C virus (HCV) infection, iron overload, and sickle cell hepatopathy. Nowadays, several oral direct-acting antiviral drugs (DAAs) have been developed and approved by the FDA for hepatitis C treatment. However, the safety and efficacy of DAAs in SCD patients remain insufficiently explored. Purpose of the study: To evaluate the efficacy and safety of administration of generic sofosbuvir (SOF) and daclatasvir (DCV) for 12 weeks in SCD patients infected with HCV. Methods: A retrospective study included 38 SCD patients infected with HCV treated with generic SOF (400 mg) and DCV (60 mg) for 12 weeks without ribavirin. The effectiveness of the HCV treatment was assessed by the sustained virologic response (SVR) at 24 weeks after the end of the treatment (SVR24). Results: The SVR24 rate was 100% (38/38).There were insignificant alterations in hemoglobin and total bilirubin levels during HCV treatment or at end of treatment (EOT). The number of anemic patients who needed blood transfusion two weeks before HCV treatment, at week 4 of treatment, and at EOT was 11 (28.9%), 3 (8%), and 1 (3%) respectively. Moreover, the reductions in serum transaminase levels from baseline were statistically significant compared to the EOT. Conclusion: Generic SOF and DCV regimens appear to be safe and effective in the treatment of chronic HCV in patients with SCD. [ABSTRACT FROM AUTHOR]

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015–2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity—a common occurrence in countries such as Italy—proved to be highly effective and safe. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a major global health concern, particularly in Egypt, due to historic schistosomiasis control efforts that inadvertently led to widespread HCV transmission. This study aimed to evaluate the efficacy of Egypt's national strategies in controlling and reducing the prevalence of HCV, including introducing sofosbuvir and implementing the "100 Million Healthy Lives" campaign. The approach includes a review of epidemiological data, an analysis of the national HCV control strategies implemented, and an assessment of their outcomes, focusing on the period from 2006 to 2022. Significant milestones were achieved, including a drastic reduction in new HCV infections from 300 per 100,000 in 2014 to 9 per 100,000 in 2022 and successful treatment of over 4 million people. Egypt has become the first country in the world to achieve the "gold tier" status based on World Health Organization criteria on the path to eradication of HCV. Egypt's comprehensive approach can serve as a model for similar endemic regions. Other nations with high HCV prevalence might benefit from adopting similar multidimensional strategies, emphasizing prevention and treatment. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose of the study Sickle cell disease (SCD) patients are at a high risk of chronic liver disease (CLD) due to chronic viral hepatitis infection such as hepatitis C virus (HCV) infection, iron overload, and sickle cell hepatopathy. Nowadays, several oral direct-acting antiviral drugs (DAAs) have been developed and approved by the FDA for hepatitis C treatment. However, the safety and efficacy of DAAs in SCD patients remain insufficiently explored. Purpose of the study To evaluate the efficacy and safety of administration of generic sofosbuvir (SOF) and daclatasvir (DCV) for 12 weeks in SCD patients infected with HCV. Methods A retrospective study included 38 SCD patients infected with HCV treated with generic SOF (400 mg) and DCV (60 mg) for 12 weeks without ribavirin. The effectiveness of the HCV treatment was assessed by the sustained virologic response (SVR) at 24 weeks after the end of the treatment (SVR24). Results The SVR24 rate was 100% (38/38).There were insignificant alterations in hemoglobin and total bilirubin levels during HCV treatment or at end of treatment (EOT). The number of anemic patients who needed blood transfusion two weeks before HCV treatment, at week 4 of treatment, and at EOT was 11 (28.9%), 3 (8%), and 1 (3%) respectively. Moreover, the reductions in serum transaminase levels from baseline were statistically significant compared to the EOT. Conclusion Generic SOF and DCV regimens appear to be safe and effective in the treatment of chronic HCV in patients with SCD.

Abstract Background The link between diabetes mellitus and chronic hepatitis C infection remains well established. It is estimated that up to one third of chronic hepatitis C patients have type II diabetes mellitus. Hepatitis C virus infection is one of the main global health burdens. Sofosbuvir and Daclatasvir are used as effective antiviral inhibitors of hepatitis C virus. The cardiovascular effects of those drugs are not well studied. We used electrocardiography and echocardiography with global longitudinal strain assessment by speckle tracking to detect their effect on cardiac function. Methods and results One hundred diabetic patients with hepatitis C infection were included in the study. Abdominal ultrasound and laboratory work up were carried out for all participants. Left ventricular systolic and diastolic function were assessed by 2D-echocardiography and global longitudinal strain, before and 3 months after treatment. Results showed significant decrease in global longitudinal strain 3 months after therapy (-21 ± 4 vs. -18 ± 7; P

Summary: Background: Economic hardship associated with chronic liver disease (CLD) may delay timely access to healthcare. Aim: To estimate the national burden of financial hardship across the spectrum of CLD in the United States (US) during the coronavirus disease 2019 (COVID‐19) pandemic. Methods: A cross‐sectional analysis was performed using the 2020–2021 US National Health Interview Survey database. The questionnaire defined financial hardship from medical bills and cost‐related nonadherence to medications in patients with CLD. We used weighted survey analysis to obtain the national estimates. Results: While 6.9% (95% confidence interval [CI]: 6.7%–7.2%) out of 60,689 US adults (weighted sample: 251 million) reported financial hardship and inability to pay medical bills; 10.6% (95% CI: 8.3%–13.4%), 18.2% (95% CI: 14.5%–22.6%), 22.6% (95% CI: 11.0%–41.0%) with hepatitis, CLD/cirrhosis, and liver cancer experienced an inability to pay their medical bills due to financial hardship, respectively. 19.8% (95% CI: 15.9%–24.5%) and 23.3% (95% CI: 12.5%–39.3%) with CLD/cirrhosis and liver cancer, respectively experienced cost‐related nonadherence to medications, compared to a tenth of US adults (10.7%, 95% CI: 10.3%–11.2%). CLD/cirrhosis demonstrated an independent association with financial hardship from medical bills and cost‐related nonadherence to medications. Overall, these disparities were more pronounced in individuals aged <65 years old. In addition, over 40% of individuals with CLD/cirrhosis reported difficulties accessing medical care during the COVID‐19 pandemic. CLD/cirrhosis showed an independent association with difficulties accessing medical care due to COVID‐19. Conclusions: Financial hardship from medical bills and cost‐related nonadherence to medication can negatively impact individuals with CLD and need further evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV. Areas covered: We review the pharmacokinetics, pharmacodynamics, and potential drug–drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs. Expert opinion: Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures. [ABSTRACT FROM AUTHOR]

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the overall treatment response of Genotype-3 Chronic HCV Pakistani Patients with or without cirrhosis to Ledipasvir plus Sofosbuvir combination. Method: In this observational study, HCV Genotype-3 patients were enrolled from Liver Center, DHQ Hospital, Faisalabad and divided into two groups, i.e., non-cirrhotic and compensated cirrhotic patients. The study spanned for a period of 24 months (November 2019 - November 2021) from the first enrollment to the last follow up. Non-cirrhotic patients received Ledipasvir/Sofosbuvir (LDV/SOF) 90/400mg for 12 weeks and cirrhotic patients received LDV/SOF with Ribavirin (RBV) for 12 weeks and without RBV for 24 weeks. The treatment efficacy in terms of sustained virological response (SVR12) was monitored 12 weeks post-treatment. The safety profile, and health-related quality of life (HRQoL) were monitored from baseline to follow-up visits. Results: Two hundred and ninety out of 309 (93.85%) non-cirrhotic and 31 out of 33 (93.94%) compensated cirrhotic patients achieved SVR-12. The safety profile of the non-cirrhotic and compensated cirrhotic patients was comparable throughout the study duration. Fatigue was the most commonly reported adverse event (AE) in non-cirrhotic and compensated cirrhotic patients, followed by headache, nausea, and fever. The HRQoL improved from baseline to follow-up visits among patients of both groups. Conclusion: It is concluded that LDV and SOF combination regimen is safe and effective for treating Genotype-3 HCV patients without cirrhosis/compensated cirrhosis, and also improves the patient’s HRQoL. [ABSTRACT FROM AUTHOR]

Hepatitis C virus core antigen (HCVcAg) testing can simplify and decrease costs of HCV infection confirmation compared to molecular testing (nucleic acid testing). We piloted HCVcAg testing for the confirmation of active infection. The study was conducted during June through December 2022 among the police and the general population of Islamabad, Pakistan age 18 years and older. Initial screening for HCV antibody was conducted using a rapid diagnostic test (RDT) for all consenting participants. Those who tested positive had venous blood samples tested for HCVcAg, platelets and aspartate aminotransferase (AST). Persons with HCVcAg values ≥3 fmol/L were defined as viremic, and they were offered treatment with direct acting antiviral (DAA) medications, sofosbuvir and daclatasvir. Aspartate aminotransferase to platelet ratio index (APRI) was calculated for each HCV infected person, and those with an APRI score <1.5 received treatment for 12 weeks, while those with APRI ≥ to 1.5 received 24 weeks of treatment. A total of 15,628 persons were screened for anti‐HCV using RDT and 643 (4.1%) tested positive. HCVcAg values of ≥3 fmol/L was found in 399/643 (62.1%), and all were offered and accepted treatment. Of those treated, 273/399 (68.4%) returned for a follow‐up SVR and HCVcAg was not detected in 261/273, a 95.6% cure rate. The pilot study demonstrated the effectiveness of reaching and treating an urban population using RDT for screening and HCVcAg for confirmation of infection and test of cure. [ABSTRACT FROM AUTHOR]

Sofosbuvir (SOF) is a P-glycoprotein (P-gp) substrate, and carvedilol (CAR) is an inhibitor of P-gp, suggesting that it may affect the oral pharmacokinetics and safety of SOF. The current study investigated the pharmacokinetic interaction of CAR with SOF and its metabolite, GS-331007, and the possible consequent toxicities in rats. To assess the pharmacokinetics of SOF and GS-331007, rats were divided into three groups; all received a single oral dose of SOF preceded with saline (SAL), verapamil (VER) as a standard P-gp inhibitor, or CAR, respectively. The serosal, plasma, and hepatic tissue contents of SOF and GS-331007 were assessed using LC-MS/MS. Renal and hepatic toxicities were assessed using biochemical and histopathological tests. Serosal and plasma concentrations of SOF and GS-331007 were increased in the presence of CAR, suggesting a significant inhibitory effect of CAR on intestinal P-gp. Simultaneously, the pharmacokinetic profile of SOF showed a significant increase in the Cmax, AUC(0-t), AUC (0-∞), t1/2, and a reduction in its apparent oral clearance. While the pharmacokinetic profile of GS-331007 was not significantly affected. However, this notable elevation in drug oral bioavailability was corroborated by a significant alteration in renal functions. Hence, further clinical investigations are recommended to ensure the safety and dosing of CAR/SOF combination. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) revolutionized the therapeutics of chronic hepatitis C. The emergence and transmission of HCV variants with resistance-associated substitutions (RASs) can undermine HCV treatment. This study aimed to assess the prevalence and temporal trends of RASs in HCV, with a particular focus on clinically relevant RASs (cr-RASs). Near-complete HCV GenBank sequences archived in the Los Alamos HCV Database were analyzed. The study period was divided into two phases: before 2011 and from 2011 onward. Identification of RASs across three DAA classes (NS3, NS5A, and NS5B inhibitors) was based on the 2020 EASL guidelines. The AASLD-IDSA recommendations were used to identify cr-RASs for three HCV genotypes/subtypes (1a, 1b, and 3) and four DAA regimens: ledipasvir/sofosbuvir; elbasvir/grazoprevir; sofosbuvir/velpatasvir; and glecaprevir/pibrentasvir. The final HCV dataset comprised 3443 sequences, and the prevalence of RASs was 50.4%, 60.2%, and 25.3% in NS3, NS5A, and NS5B, respectively. In subtype 1a, resistance to ledipasvir/sofosbuvir was 32.8%, while resistance to elbasvir/grazoprevir was 33.0%. For genotype 3, resistance to sofosbuvir/velpatasvir and glecaprevir/pibrentasvir was 4.2% and 24.9%, respectively. A significant increase in cr-RASs was observed across the two study phases as follows: for ledipasvir/sofosbuvir in subtype 1a, cr-RASs increased from 30.2% to 35.8% (p = 0.019); for elbasvir/grazoprevir in subtype 1a, cr-RASs increased from 30.4% to 36.1% (p = 0.018); In subtype 1b, neither ledipasvir/sofosbuvir nor elbasvir/grazoprevir showed any cr-RASs in the first phase, but both were present at a prevalence of 6.5% in the second phase (p < 0.001); for sofosbuvir/velpatasvir in genotype 3, cr-RASs increased from 0.9% to 5.2% (p = 0.006); and for glecaprevir/pibrentasvir, cr-RASs increased from 12.0% to 29.1% (p < 0.001). The rising prevalence of HCV RASs and cr-RASs was discernible. This highlights the necessity for ongoing surveillance and adaptation of novel therapeutics to manage HCV resistance effectively. Updating the clinical guidelines and treatment regimens is recommended to counteract the evolving HCV resistance to DAAs. [ABSTRACT FROM AUTHOR]

Summary: Background: Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct‐acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first‐line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Methods: Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. Results: In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non‐GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. Conclusion: SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first‐line therapy with SOF/VEL were not associated with lower SVRs. [ABSTRACT FROM AUTHOR]

Background: The link between diabetes mellitus and chronic hepatitis C infection remains well established. It is estimated that up to one third of chronic hepatitis C patients have type II diabetes mellitus. Hepatitis C virus infection is one of the main global health burdens. Sofosbuvir and Daclatasvir are used as effective antiviral inhibitors of hepatitis C virus. The cardiovascular effects of those drugs are not well studied. We used electrocardiography and echocardiography with global longitudinal strain assessment by speckle tracking to detect their effect on cardiac function. Methods and results: One hundred diabetic patients with hepatitis C infection were included in the study. Abdominal ultrasound and laboratory work up were carried out for all participants. Left ventricular systolic and diastolic function were assessed by 2D-echocardiography and global longitudinal strain, before and 3 months after treatment. Results showed significant decrease in global longitudinal strain 3 months after therapy (-21 ± 4 vs. -18 ± 7; P < 0.001) but other echocardiographic findings showed no significant changes. Conclusions: Sofosbuvir and Daclatasvir were associated with early left ventricular systolic dysfunction as assessed by global longitudinal strain in diabetic patients. More deterioration in left ventricular systolic function was detected among those with Child-Pough class B. Further long-term follow-up may be required. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is a global public health problem affecting millions of people worldwide. Chronic HCV infection causes long-term complications as liver cirrhosis and its consequences as hepatocellular carcinoma. The inadequate and improperly tolerated treatment options contributed to the health burden of chronic HCV. New treatment therapies had evolved that implied direct-acting antivirals (DAAs) that targeted different hepatitis C virus genomic sites. DAAs demonstrated better efficacy, patient compliance, and tolerance than former antiviral therapy. transient elastography is established as a noninvasive method for assessing hepatic fibrosis in HCV patients. Aim of the study: to demonstrate the effectiveness of DAAs (sofosbuvir-based therapy) in treating chronic HCV infection and improving hepatic fibrosis through assessment using TE. Relevant articles were identified by searching PubMed and Google Scholar databases. Conclusions: This literature review revealed significant improvement in hepatic fibrosis assessed by TE in HCV patients treated by sofosbuvir-based antiviral therapy. [ABSTRACT FROM AUTHOR]

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5–20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS‐331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on‐ and off‐dialysis studies. On the contrary, GS‐331007 exhibited a 30% reduction in the area under the plasma concentration–time curve from time 0 to 24 h (AUC0‐24h) on dialysis days compared with non‐dialysis days (AUC0‐24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS‐331007 was 9.35 (8.72–15.11) and 8.89 (8.52–14.07) mL/min, respectively. Subsequently, an alternate‐day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child–Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required. [ABSTRACT FROM AUTHOR]

Introduction: Patients with advanced hepatocellular carcinoma (HCC) have limited treatment options in the context of decompensated cirrhosis. HCC occurs in patients with hepatitis C virus (HCV) infection and cirrhosis at 1–4% per year. Direct-acting antiviral (DAA) efficacy is decreased in the presence of HCC. We present a case where immunotherapy may have resulted in HCV clearance, when DAA therapy had been ineffective. We hypothesise that immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway can reverse T-cell exhaustion and aid in the clearance of chronic HCV. Case Presentation: This case study describes a male in his 40 s identified by a re-engagement initiative for HCV, who had been unaware of his diagnosis. On further investigation he was found to have compensated for liver cirrhosis and HCC. He was treated with HCV DAA therapy (sofosbuvir/velpatasvir) and then systemic immunotherapy for HCC with atezolizumab and bevacizumab, in an attempt to downstage the disease. Hepatitis C therapy did not achieve sustained virological response, with viral relapse after the end of treatment. This, combined with ongoing alcohol use, resulted in hepatic decompensation and cessation of immunotherapy after the fifth cycle. The HCV RNA subsequently became undetectable without further DAA re-treatment. Conclusion: To our knowledge, this is the first case of HCV clearance after DAA relapse and the timing of this event after immunotherapy suggests a causal link. We hypothesise that this may be due to the reversal of antiviral T-cell exhaustion. This would therefore support further investigation into other chronic viral infections that create tumour associated with immunosuppressive microenvironments. [ABSTRACT FROM AUTHOR]

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review. [ABSTRACT FROM AUTHOR]

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post–symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post–symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment. [ABSTRACT FROM AUTHOR]

Abstract Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

ABSTRACTThe local manufacture of advanced pharmaceutical products has been a long-standing objective of health and industry policy in many developing countries, including in Latin America. This strategy has been applied to fight epidemics such as HIV/AIDS, malaria, and the COVID-19 pandemic. However, we still know little about the politics and governance that enable such arrangements, especially when there is no consent from the originator company. This study focuses on the case of Brazil, a country that is well-known for its health-industry policy, which includes the local production of direct-acting antivirals (DAAs), a new treatment for hepatitis C. We seek to explain the factors that have contributed to Brazil’s successful production of generic versions of DAAs, and, later, to the decision by the Ministry of Health (MoH) to procure drugs from multinational pharmaceutical companies rather than from local laboratories. A lack of support for domestic production by important stakeholders, the patent holder’s attempt to block domestic production and the MoH’s adoption of more modern treatment guidelines under a different procurement logic all created an unfavourable environment for local production and procurement of DAAs. Our study draws implications for middle-income countries that wish to produce drugs domestically without voluntary license agreements.