Sofosbuvir Research Articles

Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy.

To assess the efficacy and safety of the Velpatasvir (VEL)/Sofosbuvir (SOF) with or without Ribavirin (RBV) in treating patients with decompensated hepatitis C cirrhosis. We searched multiple databases for studies published from October 2010 to September 2024. Outcomes of interest were sustained viral response at 12 weeks (SVR12) and the safety of VEL/SOF with and without RBV regimens in patients with decompensated hepatitis C virus (HCV) cirrhosis. All statistical analyses were performed using R Statistics (4.4.1). We included 13 studies that enrolled 872 adult patients with decompensated cirrhosis due to HCV. The addition of RBV to the VEL/SOF regimen neither significantly improved SVR12 after the last dose of treatment [95.0% (366/391, 95% CI: 89.0-99.0) vs. 94.0% (442/481, 95% CI: 90.0-97.0); p = 0.92] nor decreased virologic relapse [1.0% (2/158, 95% CI: 0.0-8.0) vs. 6.0% (12/197, 95% CI: 3.0-10.0); p = 0.15]. VEL/SOF plus RBV therapy had a significantly higher rate of adverse events [92.0% (261/287, 95% CI: 88.0-95.0) vs. 47.0% (167/348, 95% CI: 24.0-71.0); p < 0.01] and death [7.0% (20/287, 95% CI: 2.0-16.0) vs. 2.0% (8/366, 95% CI: 1.0-4.0); p = 0.05]. However, for patients with genotype 3, adding RBV to the VEL/SOF regimen significantly improved SVR12 [87.0% (26/30, 95% CI: 71.0-98.0) vs. 45% (7/15, 95% CI: 13.0-79.0); p < 0.01] and decreased virologic relapse [0.0% (0/10, 95% CI: 0.0-31.0) vs. 100% (1/1, 95% CI: 2.0-100.0); p = 0.02]. VEL/SOF based therapy is a safe and effective treatment for patients with decompensated cirrhosis due to HCV. The addition of RBV to VEL/SOF may increase toxicity without achieving improved efficacy overall. However, the addition of RBV significantly increased the SVR12 rate and reduced the virologic relapse in genotype 3 patients. Trial Registration: PROSPERO database: CRD42023491852.

Background & objectivesGenomic diversity of Hepatitis C Virus (HCV), accessibility and long-term influence of Direct Acting Antiviral (DAA) treatment remain underexplored among HCV-infected chronic liver disease (CLD) patients in the real world. This retrospective study addressed the inadequacy of assessing the effectiveness of DAA and identify genotype-specific variations in treatment response in the context of HCV epidemiology. Additionally, real-world treatment challenges encountered during the COVID-19 pandemic and the transitional phase of implementing the National Viral Hepatitis Control Program (NVHCP) guidelines have also been addressed.MethodsThis retrospective study included 254 CLD patients from November 2017 and February 2020 to assess the effectiveness of DAA and long-term treatment outcomes among CLD patients.ResultsHCV viremia was observed in 58.26% (n = 148) patients. Patients aged 52–59 years with a history of blood transfusions exhibited a higher prevalence of active HCV infection. Two major genotypes (GT) - GT1 and GT3, and seven subtypes with few new subtypes were identified. SVR24 was achieved in 89.6% of patients receiving sofosbuvir (SOF) + daclatasvir (DCV) or SOF/ledipasvir (LDV) drug regimens. For individuals who failed to reach SVR24 (n = 13), a modified regimen (SOF + Velpatasvir (VEL) + ribavirin (Riba) for 6 months) was given and the success rate was 92.31%. GT-1a and GT-1b showed better treatment response, whereas GT-3b had a lower treatment response. Among 77 SVR24 achieved patients, 57.14% were cirrhotic and 42.86% were non-cirrhotic at the start of the therapy.Interpretation & conclusionThis study highlights genotype-specific variations in treatment response, with GT-3b exhibiting lower treatment response which highlights the need to decipher the reasons behind treatment failure for future therapeutic management.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-025-11565-3.

The accumulation of antiviral drugs, such as sofosbuvir (SOF), in aquatic environments raises growing concerns due to their persistence and potential ecological risks. This study addresses the need for effective degradation strategies by investigating the homogeneous electro-Fenton (EF) process in a Pt/carbon felt cell for the degradation and mineralization of SOF in an aqueous medium. A Box-Behnken design (BBD) was employed to optimize key operational parameters, including initial Fe2+ concentration, current intensity, and initial SOF concentration, targeting chemical oxygen demand (COD) removal as the main response. The model showed excellent predictability (R2 = 0.99), and the optimal conditions were identified as 400 mA current intensity, CSOF-0 = 0.1 mM, and CFe2+-0 = 0.1 mM. Under these conditions, 97% of SOF was degraded within 5 min, while complete mineralization was achieved within 5 h. Biodegradability tests revealed an increase in the BOD5/COD ratio to 0.41 after 2 h of electrolysis, indicating that the EF process can be effectively coupled with a biological treatment. The combined bio-electro-Fenton (bio-EF) approach successfully achieved complete mineralization, offering a cost-effective and sustainable strategy for the removal of recalcitrant pharmaceutical pollutants from water.

This investigation assessed the clinical outcomes and adverse effects of combination therapy using sofosbuvir (SOF) and daclatasvir (DCV) among dialysis-dependent patients infected with hepatitis C virus (HCV) genotypes 1b or 2a in real-world settings. We conducted a prospective, single-arm interventional trial comprising 16maintenance hemodialysis patients (14 with HCV-1b, 2 with HCV-2a). Participants received SOF-DCV combination therapy over 24 weeks with monitoring at weeks 4, 12, and 24 during treatment, plus a follow-up assessment 12 weeks post-treatment completion. The primary outcome measure was sustained virologic response at 12 weeks post-treatment (SVR12). Secondary endpoints included therapeutic tolerance and safety profiles. All 16 participants completed the prescribed treatment regimen. Demographic characteristics revealed a mean age of 57.0 years, male predominance (75%), average dialysis duration of 7.0 years, and mean body weight of 63.0 kg. Five patients (31.3%) had compensated cirrhosis. Liver function parameters remained stable throughout the study period. Rapid virologic response (RVR) was documented in 87.5% (14/16) of participants, while end-of-treatment response (ETR) and SVR12 were both achieved in 93.8% (15/16) of cases. All cirrhotic patients (5/5) ultimately attained SVR12. The therapeutic regimen demonstrated favorable tolerability, with no treatment discontinuations due to adverse events. One participant was lost to follow-up. APRI scores significantly decreased from baseline (0.56) to week 24 (0.20, p < 0.001). Reported adverse reactions included headache, fatigue, nausea (each 6.3%), and anemia (18.8%). The 12-week SOF-DCV combination demonstrated robust therapeutic efficacy and acceptable safety profiles in hemodialysis patients infected with HCV genotypes 1b or 2a, including those with compensated cirrhosis.

Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the hepatitis C virus (HCV) and has recently been incorporated into the Korean healthcare system. This study aimed to evaluate the real-world efficacy and safety of these antivirals in the South Korean population. Methods: This prospective, multicenter, observational study enrolled patients with chronic HCV treated with SOF/VEL-based regimens at six hospitals between November 2022 and January 2024. DAA-naïve patients received SOF/VEL ± ribavirin for 12 weeks. Patients who had failed prior DAA therapy received SOF/VEL/VOX for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 101 patients treated with SOF/VEL, the mean age was 64.71 years, and 40.9% were male. Genotypes 1b and 2 were identified in 40.6% and 59.4% of patients, respectively. Two patients had a history of interferon-based treatment. The mean baseline HCV RNA level was 3,088,097 IU/mL. Cirrhosis was observed in 26.7% of patients (21.8% compensated; 5.0% decompensated). Of the 101 patients, 12 were lost to follow-up. Among the 89 patients who completed follow-up, SVR12 was achieved in 100.0% (89/89), including 5 patients with decompensated cirrhosis. In the SOF/VEL/VOX group, 17 patients were treated. The mean age was 61.84 years, 29.4% were male, and four had compensated cirrhosis. One patient was lost to follow-up. SVR12 was achieved in 100.0% (16/16) of the patients who completed follow-up. No serious adverse events (≥grade 3) were reported in either group during the DAA treatment period. Conclusions: In this first prospective real-world study in South Korea, SOF/VEL-based regimens demonstrated excellent efficacy and safety, achieving 100% SVR12 in the per-protocol population, including patients with cirrhosis and prior treatment failure.

Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo.

In commercial applications, sofosbuvir (SOF) for hepatitis C is only available in tablet dosage form, resulting in minimal SOF accumulation in the liver (26.94%) due to its low intestinal permeability and high molecular weight (529.5 Da). Therefore, in this study, luminar capsule microneedles (LUCAMs) were developed, in which SOF was delivered via dissolving microneedles (DMN) attached to a branch and encapsulated in an enteric-coated hard capsule designed to dissolve exclusively in the intestinal environment. The needle on the DMN has the potential to facilitate SOF absorption in the intestine, thereby enabling maximum absorption. A thorough evaluation of DMN, branches, and capsules was conducted, encompassing formulation, characterization, differential scanning calorimetry, and dissolution time. This comprehensive evaluation demonstrated that the results obtained align with the established specifications. Furthermore, a series of evaluations, including capsule coating, revealed that the capsules dissolve selectively under intestinal pH conditions, as indicated by a hemolysis assay and irritation potential levels below 5%. These findings collectively demonstrate that the utilized biomaterial is nontoxic and nonirritating. In vitro and ex vivo permeability studies demonstrated that LUCAMs released 99.32 ± 11.92 and 203.97 ± 19.78 μg/mL SOF within 24 h, respectively. In vivo studies were conducted on two groups, namely, LUCAMs and controls, with measurements taken at 12, 24, and 36 h. The results demonstrated a significant increase in SOF concentration in the liver, reaching 1.26 ± 0.18 μg/mL in the LUCAM group by 36 h, in contrast to the control group, which was only detected at 12 h (0.83 ± 0.13 μg/mL) and not detected at 24 and 36 h. Histopathological analysis confirmed the absence of severe tissue damage, indicating that LUCAMs are a promising approach for enhancing the delivery of SOF to the liver and improving the efficacy of hepatitis C treatment.

Direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infection are endowed with sustained virological response (SVR) rates >95%. However, HCV cure does not completely eliminate the risk of hepatocellular carcinoma (HCC) development and liver decompensation. The present study investigated the impact of the administered DAA regimen on clinical long-time outcomes after SVR.Matched-pair survival analyses of 5802 chronically HCV infected patients from the German Hepatitis C-Registry compared the incidence of liver-related events 2.5 years after SVR in patients receiving either sofosbuvir (SOF)-based treatment or NS3/NS4A-protease inhibitor (PI)-containing DAA regimens. Hypothesis driven logistic regression analyses were performed to identify independent predictors for the occurrence of liver-related events.Matched-pair survival analyses revealed a borderline significant difference in the incidence of liver-related endpoints (except of HCC development) in patients receiving SOF-based treatment (4.1%) compared to PI-containing DAA regimens (2.6%) 2.5 years after SVR (p=0.061). Numerically, a trend towards a benefit of PI-based DAA treatment was observed (PI 65 events vs SOF 102 events). Hypothesis driven logistic regression analyses could not confirm SOF-based treatment as an independent predictor for the occurrence of liver-related events after HCV cure (p=0.072, OR=0.670).The incidence of liver-related events 2.5 years after HCV cure did not differ significantly between SOF-based DAA treatment and PI-containing regimens. However, numerically a trend towards a benefit of PI-based DAA treatment was observed. Therefore, a minor effect of the applied DAA regimen on the long-term incidence of liver-related events cannot be excluded.

WED-274 Real-world outcomes in patients with Voxilaprevir (VOX)/ Velpatasvir (VEL)/Sofosbuvir (SOF) treatment failure: a follow-up study

A study indicated that ravidasvir (RDV) has excellent safety and tolerability when used with sofosbuvir (SOF) to treat chronic HCV infection. The aim of this study was to determine the time taken by RDV/SOF to achieve optimum viral load suppression in chronic hepatitis C patients with or without compensated cirrhosis. Data from the open-label, multicentre, single-arm, phase II/III clinical trial (STORM-C-1) were utilized. Time‒to-event analysis via Kaplan–Meier curves was performed to determine the time required to achieve optimum viral load suppression in both the cirrhotic and noncirrhotic groups. Multivariate logistic regression analyses were performed to identify potential predictors of achieving suppression within four and eight weeks. The time to achieve optimum viral load suppression ranged from six to 85 days and from five to 148 days among noncirrhotic and cirrhotic patients, respectively. Among noncirrhotic patients, 80.6% achieved optimum viral load suppression within 4 weeks, and 92.6% achieved this within 8 weeks. Among cirrhotic patients, 76.1% and 90.4% achieved optimum viral load suppression within 4 and 8 weeks, respectively. Notably, optimum viral load suppression differs from sustained virological response (SVR12), which is defined as undetectable HCV RNA 12 weeks after treatment completion. While the study demonstrates promising early viral suppression, it does not evaluate the efficacy of a shortened regimen. Further research is needed to assess whether shorter treatment durations maintain high SVR12 rates without compromising treatment success.

Sofosbuvir (SOF) is an antiviral compound used alone for the treatment of hepatitis C or in combination with drugs such as ribavirin and ledipasvir (LED). FDA approval as monotherapy was granted in 2013 and for combination treatment of hepatitis C, in 2014. Different studies have been reported the analysis of SOF in bulk and tablet forms. However, a monograph for SOF has not yet been included in official pharmacopoeias. Therefore, no consensus in respect of identification of impurities and concerns relating to safety of the drug exists. A review of the development of stability indicating chromatographic methods for analysis of SOF was undertaken using PubMed and the Google Scholar databases from initial reports to January 2023. Our focus pertained to studies in which a stability indicating chromatographic method had been designed and validated for analysis of SOF in bulk and in tablet form alone and in combination with LED, daclatasvir (DAC), velpatasvir (VEL) and voxilaprevir (VOX) and also reported the use of stress testing. The purpose of this review is to summarize the information reported in different studies in respect of the development of stability indicating methods conducted using stress studies for the analysis of SOF and the results of such stress studies.

Objectives: To perform a comparative analysis, evaluating the efficacy and safety profiles discerningly in a cohort of liver transplant recipients and non-liver transplant recipients infected with hepatitis C and treated with direct-acting antivirals (DAA). Methods: This study is a real-life retrospective, observational analysis of individuals with chronic hepatitis C who were treated with DAA. During this period, 990 patients diagnosed with hepatitis C received DAA therapy, 165 of whom had undergone liver transplantation. Exclusion criteria included HIV-positive patients and those without a sustained virologic response (SVR) assessment. Results: The SVR was 95.8 and 95.6% in liver transplant recipients and nonrecipients, respectively (p = 0.94). The majority of patients were treated with sofosbuvir (SOF) in combination with daclatasvir, simeprevir, and ledipasvir. Ribavirin (RBV ) was co-administered to 43.2% of patients, resulting in no improvement in SVR and an increase in adverse events. Treatment of genotype 2 patients with SOF and RBV and genotype 3 patients with SOF, interferon, and RBV for only 12 weeks showed suboptimal efficacy (89.5 and 83.3%), respectively. Conclusion: The treatment of hepatitis C with DAA is as effective and safe in liver transplant patients as in non-liver transplant patients, and the prescription of RBV is inadvisable due to the increase in serious adverse events without improvement in SVR.

Objetivos: Realizar uma análise comparativa, avaliando cuidadosamente os perfis de eficácia e segurança em uma coorte de receptores de transplante de fígado e não receptores de transplante de fígado infectados com hepatite C e tratados com antivirais de ação direta. Métodos: Este estudo é uma análise observacional retrospectiva da vida real de indivíduos com hepatite C crônica que foram tratados com antivirais de ação direta. Durante esse período, 990 pacientes diagnosticados com hepatite C receberam terapia com antivirais de ação direta, 165 dos quais foram submetidos a transplante de fígado. Os critérios de exclusão incluíram pacientes HIV positivos e aqueles sem avaliação de resposta virológica sustentada. Resultados: A resposta virológica sustentada foi de 95,8 e 95,6% em receptores e não receptores de transplante de fígado, respectivamente (p = 0,94). A maioria dos pacientes foi tratada com sofosbuvir (SOF) em combinação com daclatasvir, simeprevir e ledipasvir. A ribavirina (RBV) foi administrada a 43,2% dos pacientes, resultando em ausência de melhora na resposta virológica sustentada e aumento de eventos adversos. O tratamento de pacientes do genótipo 2 com SOF e RBV e de pacientes do genótipo 3 com SOF, interferon e RBV por apenas 12 semanas mostrou eficácia subótima (89,5 e 83,3%), respectivamente. Conclusão: O tratamento da hepatite C com antivirais de ação direta é tão eficaz e seguro em pacientes transplantados hepáticos quanto em pacientes não transplantados hepáticos, e a prescrição de RBV é desaconselhável devido ao aumento de eventos adversos graves sem melhora da resposta virológica sustentada.

BackgroundAlphaviruses, including chikungunya virus (CHIKV), pose a significant global health threat, yet specific antiviral therapies remain unavailable.MethodsWe evaluated combinations of three oral directly acting antiviral drugs (sofosbuvir (SOF), molnupiravir (MPV), and favipiravir (FAV)), which are approved for other indications, against CHIKV, Semliki Forest virus (SFV), Sindbis virus (SINV), and Venezuelan Equine Encephalitis virus (VEEV) in vitro and in vivo. We assessed antiviral efficacy in human skin fibroblasts and liver cells, as well as in a mouse model of CHIKV-induced arthritis.FindingsIn human skin fibroblasts, synergistic antiviral effects were observed for combinations of MPV + SOF and FAV + SOF against CHIKV, and for FAV + SOF against SFV. In human liver cells, FAV + MPV conferred additive to synergistic activity against VEEV and SINV, while SOF synergized with FAV against SINV. In mice, MPV improved CHIKV-induced foot swelling and reduced systemic infectious virus titres. Combination treatment with MPV and SOF significantly reduced swelling and infectious virus titres compared to monotherapies of each drug. Sequencing of CHIKV RNA from joint tissue revealed that MPV caused dose-dependent increases in mutations in the CHIKV genome. Upon combination therapy of MPV with SOF, the number of mutations was significantly lower compared to monotherapy with several higher doses of MPV.InterpretationCombining these approved oral nucleoside analogues confers potent suppression of multiple alphaviruses in vitro and in vivo with enhanced control of viral genetic evolution in face of antiviral pressure. These drug combinations may ultimately lead to the development of potent combinations of pan-family alphavirus inhibitors.FundingThis work was supported by a PhD fellowship granted to S.V. by the Research Foundation – Flanders (FWO) (11D5923N). L.D.C. was also supported by Research Foundation – Flanders (FWO) PhD fellowship (11L1325N). Dr. Polyak and Schiffer are partially supported by R01AI121129.

Objective: To determine the frequency of sustained virologic response (SVR) of Daclatasvir (DCV) plus Sofosbuvir (SOV) for the management of HCV genotype 3 infections in non-cirrhotic patients. Study Design: Prospective, observational study. Place and Duration of Study: Gastroenterology department, Shifa International Hospital Islamabad, 06 months (May to November 2019). Methodology: Total 75 diagnosed and treatment- naive patients of chronic HCV genotype 3, in whom liver cirrhosis was ruled out by abdominal ultrasound, were included in the study, by non-probability convenience sampling. A combination of DCV (60mg) and SOV(400mg) orally once daily for 12 weeks was given to all and were followed up in the OPD for 12 weeks after treatment. After 12 weeks of completion of treatment, HCV PCR was checked to evaluate the SVR after 12 weeks (SVR-12). Results: Out of 75 patients, male patients were 56% while female patients were 44%. The mean age was 48.65 ± 13.72 years. Diabetes mellitus was present in 62.7% of the patients. SVR-12 was achieved in 85.3% which showed insignificant association with gender (p-value 0.916), diabetes mellitus (p-value 0.455) and age (p-value 0.076). Conclusion: Achieving an SVR-12 rate of 85.3% depicts that the combination of DCV and SOV is extremely efficient in treating the HCV genotype 3, Its efficacy is consistent across patients, regardless of age, gender, or diabetes mellitus.

Background Tick-borne encephalitis (TBE) is a neurological disease caused by the tick-borne encephalitis virus (TBEV). Despite available vaccines, breakthrough infections occur, some fatal. Objectives As no antiviral therapy for TBE is currently approved, this study evaluated the in vitro activity of already licenced remdesivir (RDV) and sofosbuvir (SOF) for possible drug repurposing against TBEV. Methods TBEV was cultured in A549 cells, and the inhibitory effects of RDV (GS-5734), its parent nucleotide GS-441524, and SOF (GS-7977) were assessed. Results After 78 h, RDV demonstrated significantly lower EC50 values than SOF (0.14 vs. 11 µM) based on TBEV RNA levels measured by RT-qPCR. RDV also had a lower mean EC50 (0.55 µM) compared to GS-441524 and SOF (>8.9 and 13.1 µM, respectively) using crystal violet staining after 5 days. After 11 passages of TBEV in the presence of RDV, emergence of virus with a higher EC50 (1.32 vs. 0.55 µM) was detected with two mutations (L3122F and Y3278F) in NS5, the viral RNA-dependent RNA polymerase (RdRp), and one substitution in envelope (E) protein (E402G). Similarly, SOF resistance appeared after 20 passages, increasing EC50 values (35.5 vs. 10 µM). Conclusion RDV exhibits potent in vitro antiviral activity against TBEV via specific targeting of the viral RdRp as confirmed by the emergence of resistance-associated double NS5 substitutions in vitro in the presence of RDV. While the potential in vivo implications of the observed RDV resistance remain to be determined, these in vitro data support further assessment of RDV for the treatment of TBEV infection.

BackgroundIn conjunction with other antiviral medicines, sofosbuvir (SOF) is an essential therapy for chronic hepatitis C. There is some debate over its influence on hepatic fibrosis. The use of nanotechnology in treatment has gained popularity, with the goal of delivering therapeutic substances to the liver to increase efficacy and decrease adverse effects. The aim of this study was to demonstrate the protective effect of sofosbuvir and the efficacy of incorporating nanoparticle galactosylated taurocholate bilosomal formula to SOF on thioacetamide-induced liver fibrosis.MethodsRats were divided into 7 groups: normal control, SOF, SOF encapsulated in galactosylated taurocholate bilosomal formula (nano-SOF), galactosylated taurocholate bilosomal formula (nanoparticle), thioacetamide (TAA), TAA-SOF and TAA-nano-SOF. Liver fibrosis was induced by TAA (200 mg/kg) intraperitoneal injection twice per week for 8 weeks. SOF, nanoparticle and nano-SOF were given (40 mg/Kg/day) orally from day one of the study. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and tissue transforming growth factor beta (TGF-β) were assessed. Also, histopathological assessment of hepatic tissue was done.ResultsAdministration of SOF and TAA to normal rats resulted in significant increase in serum AST, ALT, ALP and tissue TGF-β1 levels with variable degree of liver fibrosis. Additionally, rats in TAA group that received SOF therapy did not exhibit improved liver functions, TGF-β1 level and liver fibrosis score. However, administering nano-sofosbuvir prophylactically to TAA-treated rats resulted in a considerable improvement in liver function tests, TGF-1 levels, with liver fibrosis score regression.ConclusionIn contrast to free sofosbuvir, SOF encapsulated in galactosylated taurocholate bilosomal formula (nano-SOF) displayed hepatoprotective effects in rat with thioacetamide-induced hepatic fibrosis. These findings strongly support the concept that galactoylatedbilosomes are promising nanocarrier for the targeted delivery of sofosbuvir to the liver.

IntroductionDirect antiviral agents (DAAs) have dramatically changed the landscape of liver diseases associated with chronic hepatitis C virus (HCV) infection. However, limited data are available on the antiviral effect of sofosbuvir (SOF) + velpatasvir (VEL) ± ribavirin (RBV), SOF + VEL + voxilaprevir (VOX), and glecaprevir (GLE) + pibrentasvir (PIB) in treating patients infected with HCV GT3 in a real-world setting.MethodsUsing the EMBASE, PubMed, and Cochrane Library databases, articles were screened from 1 January 2016 to 1 June 2024. The sustained virologic response (SVR) rates were analyzed using the Freeman–Tukey double arcsine transformation in a random-effects model in R4.1.0 software.ResultsWe recruited 3,177 patients with HCV GT3 in 19 studies from 9 countries. The pooled SVR12/24 rate of the three evaluated regimens was 94.00% (95% CI: 90.87-96.59%). Furthermore, the SVR rate was 83.81% (95% CI: 75.70-90.62%) in patients receiving SOF+VEL+VOX; 94.98% (95% CI: 92.02-97.33%) in patients receiving SOF+VEL ± RBV; and 96.96% (95% CI: 93.20-99.45%) in patients receiving GLE+PIB. The pooled SVR12/24 rate of the three regimens was 95.70% (95% CI: 91.74-98.58%) and 90.50% (95% CI: 83.50-95.90%) in non-cirrhotic and cirrhotic patients, respectively. The pooled SVR rate was 96.79% (95% CI: 93.37-99.13%) and 88.41% (95% CI: 82.67-93.22%) in treatment-naive and treatment-experienced patients, respectively.ConclusionSOF+VEL ± RBV, GLE+PIB, and SOF+VEL+VOX had good antiviral effectiveness for chronic HCV-GT3 infection in real-world settings. Factors such as cirrhosis and treatment experience, especially previous DAA treatment failure, may influence the SVR rate.

Managing patients with chronic hepatitis C and progressive liver conditions poses significant challenges for healthcare professionals. This research sought to evaluate and compare the clinical outcomes and patient-reported treatment experiences of individuals with chronic hepatitis C, differentiating between those with and without cirrhosis, all of whom were receiving standard direct-acting antiviral (DAA) therapy. This prospective cohort study enrolled outpatients who were diagnosed with hepatitis C virus (HCV) infection and who were recruited from a major public tertiary care hospital. The participants received a standard 12-week antiviral regimen consisting of 400 mg of sofosbuvir (SOF) and 60 mg of daclatasvir (DCV) once daily, with or without ribavirin (RBV) at a dose of 400 mg taken two to three times daily. The primary outcome was the cure rate, which was defined as an undetectable viral load at the end of the 12-week treatment period. The secondary outcomes included patient-reported outcomes (PROs), such as health-related quality of life (HRQoL), which were measured via the EuroQol 5-Dimensions 3-Levels (EQ-5D-3 L) questionnaire, and work productivity loss, which was assessed via the Work Productivity and Activity Impairment (WPAI) questionnaire. A total of 300 participants were assessed, comprising 150 cirrhotic and 150 noncirrhotic patients. Group B (cirrhosis) had a greater proportion of treatment-experienced patients and elevated aspartate aminotransferase (AST) levels (48 ± 22 vs. 131 ± 165, p &lt; 0.001), along with significantly lower platelet counts (p = 0.024). An end-of-treatment response (ETR) was observed in 92.7% of patients without cirrhosis, compared to a significantly lower rate of 52.7% in those with cirrhosis (p &lt; 0.001). A significant increase in HRQoL was noted in both groups across all the EQ-5D-3 L domains (p &lt; 0.001); however, patients with cirrhosis experienced relatively smaller improvements in the areas of pain/discomfort and anxiety/depression. A small subset of noncirrhotic patients showed no improvement in mobility (−0.59 ± 0.62). Regarding work productivity, both groups experienced substantial reductions in overall impairment (43.0% in noncirrhotic patients, 32.3% in cirrhotic patients), absenteeism, and activity limitations (p &lt; 0.001). However, presenteeism increased slightly in both groups, suggesting a return to work with residual functional limitations. The study concluded that SOF-based regimens were highly effective in noncirrhotic patients, who showed greater improvements in virological response, quality of life, and work productivity. In contrast, cirrhotic patients demonstrated lower treatment response rates and smaller gains in patient-reported outcomes despite receiving similar therapies.