Search Results (349)

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. Full article

Background: Hepatitis C virus (HCV) remains a significant public health concern in Thailand, with genotype-specific, drug-dependent variations influencing treatment response and disease progression. Despite the availability of pan-genotypic direct-acting antivirals (DAAs), genotype surveillance remains essential for optimizing national elimination strategies. This study thus aims to characterize the molecular distribution of HCV genotypes in northern Thailand. Methods: We conducted a retrospective molecular epidemiological study on 1737 HCV-infected patients who attended the Clinical Microbiology Service Unit (CMSU) Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University between April 2016 and June 2024. HCV genotyping was performed using Sanger sequencing and reverse hybridization line probe assay (LiPA). Results: Genotype 3 was the most prevalent (36.6%), followed by genotype 1 (35.8%) and genotype 6 (27.2%). Subtype 3a (27.2%) predominated, along with 1a (22.1%), 1b (12.6%), and genotype 6 subtypes including 6c to 6l (13.5%) and 6n (6.6%). Males had a higher prevalence of genotype 1, while genotype 3 was more common among females. Temporal analysis revealed a relative increase in genotype 6 prevalence since 2021. Genotype 6 also exhibited significantly higher median viral loads compared to genotypes 1 and 3 (p < 0.0001). Conclusions: This study provides updated evidence on the shifting distribution of HCV genotypes in northern Thailand, particularly the increasing prevalence of genotype 6. These findings underscore the importance of continued molecular surveillance to guide genotype-specific treatment strategies and support Thailand’s 2030 HCV elimination goals. Full article

Backgrounds: Direct-acting antiviral (DAA) therapy, which achieves a high sustained virological response (SVR) rate, has been established as a standard treatment for patients with hepatitis C virus (HCV) infection. However, the risk factors for postoperative recurrence in patients with HCV-related hepatocellular carcinoma (HCC) detected after the achievement of an SVR by DAAs are unknown. Methods: The clinical records of 95 patients with initial HCV-related HCC detected after DAA-SVR achievement, who underwent liver resection between September 2014 and December 2020, were retrospectively reviewed. Patients with major vascular invasion and/or SVR achievement induced by interferon-based therapy were excluded. In this study, the patients were divided into two groups according to their alcohol intake status: without alcohol abuse (<80 g of ethanol each day for at least 5 years, n = 85) and with (continuous) alcohol abuse (n = 10). The risk factors for recurrence after liver resection were investigated, with special reference to the alcohol intake status. Results: The 3- and 5-year disease-free survival (DFS) rates after liver resection were 68.7% and 55.3%, respectively. Univariate and multivariate analyses identified alcohol abuse [hazard ratio (HR) 3.36, p = 0.004] and tumor size (HR 2.53, p = 0.010) as independent risk factors for postoperative recurrence. The 3- and 5-year postoperative DFS rates were 72.2% and 61.5% for patients without alcohol abuse and 40.0% and 13.3% for those with alcohol abuse (p = 0.001). Conclusions: Continuous alcohol abuse is a risk factor for recurrence after surgery of HCC detected after the achievement of DAA-SVR. Full article

Background/Objectives: Direct-acting antiviral (DAA) therapy has been highly successful in treating chronic hepatitis C (CHC). The nationwide Treatment as Prevention of Hepatitis C (TraP HepC) initiative that was launched in Iceland in 2016 utilized liver stiffness measurements (LSM) to assess liver fibrosis at baseline and follow-up. We aimed to determine changes in liver stiffness among patients following treatment with DAAs and evaluate risk factors associated with hepatic fibrosis. Methods: Eligible CHC patients with liver stiffness of >9.5 kilopascals (kPa) before DAA treatment were invited for a follow-up visit in 2024. Risk factors for cirrhosis were registered, LSM performed, and liver enzymes, blood lipids, and glucose levels measured. Changes in liver stiffness were compared to baseline measurements, and correlations with risk factors were analyzed. Results: A total of 96 patients had LSMs > 9.5 kPa at treatment initiation. During the follow-up period, 61 were eligible for participation, 38 consented, and 34 (35%) died. The total follow-up was 258.3 person-years. The median follow-up period between measurements was 7.1 years. The median liver stiffness decreased from 17.2 kPa to 7.3 kPa (p < 0.01), and 80% of those with cirrhosis (>12.5 kPa) regressed to non-cirrhotic values. High BMI and daily alcohol consumption were significantly associated with increased liver stiffness in 8% of patients. Conclusions: In this single-arm, pre-post pilot study, liver stiffness regressed significantly in 92% of patients who were cured of CHC. Patients with other persistent risk factors following cure, such as obesity and alcohol abuse, were the only patients who had increased liver stiffness at the end of follow-up. Full article

The whitefly is among the main pests of crops, especially solanaceous and cucurbitaceous plants. The massive use of pesticides for its control has led to an increase in the pest’s resistance to different groups of insecticides and to environmental contamination. The use of biopesticides for its control is a sustainable alternative for the environment. The objective of this study was to evaluate the efficiency of two biopesticides based on entomopathogenic fungi against eggs, nymphs, and adults of whitefly in eggplant in a greenhouse. The treatments consisted of Cordyceps javanica, Beauveria bassiana, a commercial insecticide (i.e., Spirotetramat), and a control (no application). A completely randomized design was used with 16 repetitions per treatment, and the non-parametric Kruskal–Wallis test was applied. Mortality was recorded on five dates after application (DAA). The sampling data were transformed to efficiency (%). The biopesticides were found to be effective in controlling whiteflies in all developmental stages during the evaluation days. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

Previous studies have shown that foliar spraying with a 0.3% CaCl₂ + 0.3% MgCl₂ solution can mitigate the “sugar receding” phenomenon in fruit pulp, partly by regulating sugar conversion in the pulp of ‘Feizixiao’ litchi (Litchi chinensis Sonn.). Given that calcium-dependent protein kinases (CDPKs) in plants regulate sugar metabolism by modulating the activity of key sugar conversion enzymes, this study investigated the expression response of CDPK genes in ‘Feizixiao’ litchi pulp to foliar calcium–magnesium nutrient treatment and their regulatory characteristics on sugar conversion. After the fruit set, ‘Feizixiao’ litchi trees were subjected to three consecutive foliar spray applications of 0.3% CaCl₂ + 0.3% MgCl₂, with water spraying as the control. The dynamic changes in peel h values and soluble sugar and monosaccharides, water-soluble calcium (Ca²⁺) and magnesium (Mg²⁺), plant hormones, and the concentration of CDPKs in the pulp were compared throughout fruit development. Key differentially expressed members of the CDPK gene family were screened through real-time quantitative PCR analysis. The results showed that the peel color transition occurred earlier in the control (CK) than in the treatment (T), but the coloration process accelerated in the treated fruit, leading to no significant difference in peel h values between the groups at 76 days after anthesis (DAA), when both reached the lowest levels. The total of soluble sugar in the pulp peaked at 70 DAA in both groups, but while the CK exhibited a significant decline thereafter, T maintained stable sugar levels, thereby mitigating the “sugar receding” phenomenon. Water-soluble calcium and water magnesium levels were significantly higher in the T at 42 and 63 DAA, with water calcium remaining significantly higher at 70 DAA. Furthermore, sucrose, glucose, fructose, abscisic acid (ABA) contents, and CDPK concentration were significantly higher in the T at 70 and 76 DAA. The CDPK gene family members LcCDPK1, LcCDPK2, LcCDPK3, LcCDPK4, LcCDPK5, LcCDPK9, LcCDPK15, and LcCDPK17 were upregulated in response to T. Among them, LcCDPK1, LcCDPK4, LcCDPK5, LcCDPK9, and LcCDPK17 were identified as key structural genes due to their significant correlation with soluble sugar content and CDPK concentration, as well as their differential expression between T and CK. In conclusion, foliar calcium–magnesium nutrient treatment upregulates the expression of these five CDPK gene family members by increasing the ABA levels in the pulp, leading to more CDPK accumulation. This accumulation inhibits sugar conversion and promotes sucrose and fructose accumulation, thereby mitigating the “sugar receding” phenomenon in ‘Feizixiao’ litchi pulp. Full article

Chile contributes 4% of global hazelnut (Corylus avellana L.) production, mainly developed in temperate regions with high autumn rainfall and humidity during harvest, which can compromise nut quality and increase postharvest losses. Thus, synchronizing harvests has become a critical aspect for growers in the southern region of Chile. This study focused on the effects of ethephon (ETH) spraying on trees to optimize nut drop timing and assess its impact on yield optimization and its influence on vegetative growth and inflorescence activity. From the 2020/2021 to the 2022/2023 seasons, experiments were conducted on a commercial hazelnut orchard of Tonda di Giffoni (TDG) planted in southern Chile. Four ETH (0, 250, 500, 1000 mg L⁻¹) treatments were sprayed 15 days preharvest and denoted as ETHA (sprayed 2020/2021) and ETHB (sprayed twice, in 2020/2021 and 2021/2022). Nut drop synchronization was periodically monitored at 7, 15, 21, 28, and 35 days after application (DAA), along with industrial quality parameters (nut weight, kernel yield) and inflorescence activity. In the first season, ETH significantly synchronized nut drops, achieving optimal results at 15–28 DAA with ETH 250 and 500, while ETH 1000 induced earlier drops but reduced yields. Total nut yield varied among seasons and demonstrated consistent performance of ETH 250, identified as the most efficient treatment for balancing nut drop timing. Industrial parameters showed seasonal differences but no adverse effects on nut quality. Conversely, the inflorescence activity remained unaffected by ETH concentrations. ETHA and ETHB treatments influenced tree shoot length variably across three seasons, showing significant concentration and seasonal interaction effects. These results demonstrate that ETH effectively synchronizes hazelnut harvests under temperate conditions, reducing post-harvest losses and optimizing logistics without compromising yield or quality. Full article

With the intensification of the population aging worldwide, neurological disorders (NDs) are seriously threatening human society. Mulberry, a traditional economic crop, is a significant medicinal plant. Increasing evidence suggests that phytochemicals from mulberry play critical roles in the prevention and treatment of NDs. This paper reviews the recently reported phytochemicals from mulberry with neuroprotective effects and systematically summarizes neuroprotective mechanisms and their classifications. Based on their origins from different parts of mulberry, the extracts with neuroprotective effects are classified into mulberry fruit extract and mulberry leaf extract. According to the compound structures, the compounds are divided into flavonoids, Diels–Alder-type adducts (DAAs), benzofurans, quinones, stilbenes, and alkaloids. This aims to provide a future reference for their pharmaceutical development and utilization. Full article

Background: There is still debate whether ribavirin should be added to direct-acting antivirals (DAAs) for the management of treatment-experienced individuals with non-genotype-1 hepatitis C. This study compared the efficacy and safety of adding ribavirin to sofosbuvir-based combinations compared to sofosbuvir-based regimens alone in treating non-genotype 1 hepatitis C virus (HCV) in individuals who have been previously treated. Methods: We searched Cochrane CENTRAL, PubMed, SCOPUS, CINAHL and preprint databases from inception to September 2023 for randomized controlled trials (RCTs) that compared sofosbuvir-based regimens with ribavirin to sofosbuvir-based regimens alone in previously treated individuals with non-genotype 1 HCV infection. Data extraction and quality of study assessments were performed by two independent authors, and synthesis was performed using bias-adjusted models, heterogeneity using I2, and publication bias using funnel plots. Results: Eight RCTs compared sofosbuvir-based combinations with and without ribavirin were included. Overall, the addition of ribavirin to sofosbuvir, compared to sofosbuvir alone, did not show a benefit in achieving sustained virological response (SVR) (OR 0.91, 95% CI 0.26–3.17, I2 = 70.0%) with moderate certainty in Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence. In subgroup analysis, there was no benefit of adding ribavirin to sofosbuvir in individuals with non-genotype 1 HCV. The additional ribavirin was associated with increased adverse events (OR 2.03, 95% CI 1.58–2.6, I2 = 8.0%) and treatment discontinuation (OR 1.81, 95% CI 0.78–4.28, I2 = 0.0%). Conclusions: The moderate certainty evidence suggests that adding ribavirin to sofosbuvir-based regimens may not confer benefit in achieving SVR in previously treated individuals with non-genotype 1 HCV but increases the odds of adverse events and treatment discontinuation. More evidence is needed on the effect of additional ribavirin in achieving SVR in individuals with decompensated cirrhosis. Registration: The protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022368868). Full article

Background: The triglyceride-glucose (TyG) index has emerged as a novel surrogate marker of insulin resistance, but its changes after hepatitis C virus (HCV) eradication remain unclear. This study aimed to evaluate changes in the TyG index following direct-acting antiviral (DAA) treatment. Methods: HCV-infected patients achieving sustained virological response 12 weeks post-treatment (SVR12) were prospectively enrolled from May 2015 to June 2023. Exclusion criteria included the following: (1) failure to achieve SVR12; (2) use of anti-diabetes or anti-hyperlipidemia medications; and (3) hepatitis B virus or human immunodeficiency virus co-infection. Changes in lipid profiles, TyG index, and homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated from baseline to SVR12. Insulin resistance was defined as HOMA-IR ≥ 2.5. The optimal TyG index cut-off for predicting insulin resistance was determined using the Youden Index. Results: A total of 111 patients (median age: 61.0 years; 45.9% male) were included. The TyG index correlated positively with HOMA-IR (Pearson’s r = 0.32, p < 0.001). Among patients with pre-existing insulin resistance, significant improvements were observed at SVR12 in both HOMA-IR (4.0 [IQR: 3.1–5.4] vs. 2.5 [IQR: 2.0–3.9]; p < 0.001) and TyG index (8.47 [IQR: 8.08–8.68] vs. 8.36 [IQR: 8.00–8.71]; p = 0.028). Using 8.27 as the optimal TyG index cut-off, similar improvements were noted in HOMA-IR (2.8 [IQR: 2.0–4.3] vs. 2.3 [IQR: 1.5–3.8]; p = 0.031) and TyG index (8.62 [IQR: 8.46–8.83] vs. 8.52 [IQR: 8.27–8.89]; p = 0.003). Conclusions: The TyG index is a valuable tool for monitoring changes in insulin resistance after HCV eradication, particularly in patients with baseline insulin resistance. Full article

Background: Chronic hepatitis C virus (HCV) infection significantly impairs health-related quality of life (HRQoL) and poses a substantial global health concern. Direct-acting antiviral (DAA) therapies have revolutionized HCV treatment, but their impact on HRQoL, particularly considering clinical and psychological factors, requires further investigation. This study aimed to evaluate the influence of DAA therapy on HRQoL in Romanian patients with chronic HCV infection, analyzing the effects of treatment on HRQoL and the role of associated factors. Methods: A prospective, single-center study was conducted on 90 HCV-infected patients treated with a 12-week DAA regimen (Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir). HRQoL was assessed at baseline (BSL), end of treatment (EOT), and 12 weeks post-treatment (SVR) using the WHOQOL BREF questionnaire. Clinical data, including fibrosis degree, prior PegIFN treatment, and psychological assessments (HADS, PSS), were collected. Statistical analyses examined HRQoL trends and associations with clinical and psychological parameters. Results: Significant improvements in HRQoL were observed across all domains over time (p < 0.0001). Gender and residence did not significantly influence HRQoL changes. Fibrosis severity and prior PegIFN treatment had no significant impact on HRQoL progression. However, comorbidities such as anemia and chronic kidney disease moderated improvements in specific HRQoL domains. Anxiety also affected HRQoL, while perceived stress and depression did not show significant effects. Conclusions: DAA therapy significantly enhances HRQoL in HCV-infected patients. While clinical and treatment-related factors had limited influence, comorbidities and anxiety played a moderating role. These findings underscore the importance of personalized care and integrated mental health assessments in HCV management. Full article

Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers of hepatocellular carcinoma (HCC). Despite the availability of an effective HBV vaccine since the 1980s, millions remain chronically infected due to the persistence of covalently closed circular DNA (cccDNA) as a reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs and interferon, effectively suppress viral replication but fail to eliminate cccDNA, underscoring the urgent need for innovative therapeutic strategies. Direct-acting antiviral agents (DAAs), which have revolutionized HCV treatment with high cure rates, offer a promising model for HBV therapy. A particularly attractive target is the intrinsically disordered region (IDR) of the HBx protein, which regulates cccDNA transcription, viral replication, and oncogenesis by interacting with key host proteins. DAAs targeting these interactions could inhibit viral persistence, suppress oncogenic signaling, and overcome treatment resistance. This review highlights the potential of HBx-directed DAAs to complement existing therapies, offering renewed hope for a functional HBV cure and reduced cancer risk. Full article

Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens. Full article

Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk. Full article