Search Results (46)

The World Health Organization targets hepatitis C virus (HCV) elimination as a public-health threat by 2030. Phetchabun province, in lower northern Thailand, has historically reported one of the country’s highest HCV seroprevalence rates. We describe a province-wide, decentralized test-to-treat micro-elimination program implemented within Thailand’s universal health-coverage system. Adults aged 35–64 years (2020–2024) and individuals born before 1992 (late 2023) across all 11 districts were screened using fingerstick anti-HCV rapid diagnostic tests at sub-district health-promoting hospitals. Reactive participants underwent confirmatory HCV-RNA testing at three regional nodes. Eligible patients received pangenotypic sofosbuvir/velpatasvir for 12 weeks, with ribavirin added for cirrhosis. Sustained virological response at 12 weeks post-treatment (SVR12) was the primary outcome. Of 400,567 targeted individuals, 389,547 (97.3%) were screened; 18,340 (4.71%) were anti-HCV reactive. Confirmatory HCV-RNA testing was completed in 14,845 (80.9%), of whom 10,996 (74.1%) had active infection. Of 8961 treatment-eligible patients, 8842 (98.7%) received DAA therapy. Among 6719 evaluable for SVR12, 6474 (96.4%) achieved cure. This simplified, domestically financed, decentralized test-to-treat model achieved WHO-target-level diagnosis, treatment, and cure rates at provincial scale, offering a scalable framework for HCV micro-elimination in low- and middle-income countries. Full article

Background/Objectives: Chronic hepatitis C (CHC) infection is an independent risk factor for developing type 2 diabetes mellitus (T2DM). However, it is unknown if antiviral treatment, especially with direct-acting antivirals (DAAs), changes long-term glycemic outcomes. Methods: We conducted a retrospective comparative cohort study of 2489 patients with chronic hepatitis C (CHC) in southern Taiwan between 2005 and 2022 who underwent treatment with either an interferon (IFN)-based or direct-acting antiviral agent (DAA) regimen. Given the distinct treatment eras of IFN and DAA therapies, potential temporal confounding was considered in the analytical design. Patients with existing diabetes or co-infections were excluded. The incidence of new-onset T2DM and longitudinal HbA1c levels were compared between treatment groups over a mean follow-up period of 2.56 years. Results: DAA-treated patients demonstrated a lower crude cumulative incidence of T2DM compared with IFN-treated patients (2.46% vs. 6.91%). However, adjusted analyses did not demonstrate a statistically significant difference between treatment groups. The cumulative risk appeared to plateau after the third year among DAA recipients. Post-therapy, HbA1c levels remained stable in both groups at between 5.5% and 6.5% over as long as five years. Splitting regression revealed that BMI ≥ 30 kg/m², and not treatment type or achieved SVR, was an independent T2DM risk factor. The lowest rates of diabetes incidence were associated with pan-genotypic DAA regimens. Conclusions: DAA-treated patients showed lower crude T2DM incidence than IFN-treated patients; however, this difference was not consistently significant after adjustment for baseline factors. Viral eradication may be associated with favorable metabolic trends; however, the present findings do not establish a causal protective effect against incident T2DM. While increased BMI remained an independent predictor of post-treatment diabetes risk. Full article

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) therapy, yet resistance-associated substitutions (RASs) remain a concern in specific clinical contexts. Here, we present a database-derived global overview of HCV RASs by analyzing 19,449 publicly available sequences across multiple genotypes and subtypes, encompassing both untreated and previously treated infections, in the NS3, NS5A, and NS5B genomic regions. We demonstrate a markedly heterogeneous distribution of RASs shaped by viral genotype, geographic origin, and treatment era. Importantly, RASs against pan-genotypic NS3 protease inhibitors (glecaprevir and voxilaprevir) were rare (generally <1% across genotypes). In contrast, NS5A inhibitors showed greater vulnerability, with the Y93H substitution detected at notable frequencies in major genotypes (3.2–7.0%) and near-universal resistance-associated substitutions (e.g., 100% Q30S) observed in the rare genotype 8. The NS5B nucleotide analogue sofosbuvir retained a high genetic barrier, with the canonical S282T substitution detected only sporadically (2.1% of genotype 4 sequences). At the population level, geographic heterogeneity was evident, with higher RAS frequencies observed in specific regions, alongside pronounced data gaps in high-prevalence areas of Africa. Temporal analyses revealed an increase in NS3 and NS5A RASs following the introduction of first-generation DAAs, with NS5A substitutions persisting into the current interferon-free era, whereas NS5B resistance remained consistently rare across all treatment periods. Together, these findings provide a global, population-level overview of resistance-associated HCV diversity and reinforce the durability of high-barrier regimens while highlighting persistent genotype-specific vulnerabilities with implications for antiviral resistance surveillance and HCV elimination efforts. Full article

Over the past decade, significant progress has been made in the treatment of chronic hepatitis C virus (HCV) infection. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV infection, offering nearly 100% efficacy. Furthermore, additional therapeutic regimens with pangenotypic efficacy have been registered. These drugs are also characterized by a few adverse events and good treatment tolerance. As DAA therapy is now accessible to virtually all patients, including those with multimorbidity who often take multiple medications, drug interactions (DDIs) have become a significant clinical challenge. One of the groups of patients who are frequently infected with HCV is those with mental disorders. Due to frequently overlapping metabolic pathways, DDIs can occur, affecting the effectiveness of both psychiatric and antiviral therapy. Knowledge of these interactions is crucial in these cases and influences patient management. This paper discusses the most significant interactions between pangenotypic DAA regimens and psychotropic medications. Full article

Pangenotypic direct-acting antivirals (pDAAs) have transformed hepatitis C virus (HCV) treatment. In Italy, sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are available. While both show similar efficacy, differences in patient profiles and potential drug–drug interactions (DDIs) may influence treatment choice. This study examined factors affecting pDAA selection and potential prescribing gaps. Using administrative databases (2018–2023) covering 3.7 million citizens, HCV patients were divided into SOF/VEL and GLE/PIB cohorts and compared by demographic, clinical, and therapeutic data. Among 5565 patients, 2837 (51%) received SOF/VEL and 2728 (49%) received GLE/PIB. SOF/VEL patients were older (60.8 vs. 57.6 years, p < 0.001) and had more comorbidities: diabetes (24% vs. 17%), mental disorders (22% vs. 14%), cancer (14% vs. 9%), and cardiovascular disease (31% vs. 22%). Hospitalization rates were higher (19% vs. 13%), as were exemption codes for chronic hepatitis (58% vs. 50%) and hypertension (32% vs. 23%). Polypharmacy was more common with SOF/VEL; 25% used ≥10 non-pDAA drugs (vs. 17%), and mean medications per patient were higher (6.3 ± 5.6 vs. 4.9 ± 5.2). SOF/VEL was often used for older, frailer patients, likely due to a more favourable DDI profile. These prescribing trends highlight the importance of tailoring pDAA choice to patient comorbidity profiles, ensuring appropriate and individualized HCV treatment. 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

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

Hepatitis C virus (HCV) eradication is usually associated with dyslipidemia. Most studies in this field have focused on genotype-specific direct-acting antivirals (DAAs), with research on pangenotypic DAAs being limited. This study examined how two pangenotypic DAA regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), affect lipid profiles and insulin resistance after viral eradication in chronic HCV patients. A total of 100 patients (57 with GLE/PIB and 43 with SOF/VEL) treated between September 2020 and January 2022 were included in the retrospective analysis. This study found a significant increase in LDL and TC levels after treatment (p < 0.001), but no significant changes in triglycerides, high-density lipoprotein, HbA1C, or the Homeostatic Model Assessment of Insulin Resistance. According to a logistic regression analysis, higher baseline LDL or TC and lower baseline glucose are predictors of the degree of increase in LDL or TC following a sustained virological response. Both pangenotypic DAA regimens significantly impact lipid profiles, particularly LDL and TC, but not insulin resistance. This study emphasizes the need for more research into the long-term metabolic effects of DAAs. Full article

The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally. Full article

The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse β-fold (residues 441–456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors. Full article

Hepatitis C is regarded as a global health issue caused by hepatitis C virus (HCV) infection. HCV is targeted for elimination by 2030 as a global public health goal. However, the COVID-19 pandemic has changed human circulation and prevented access to diagnostics and treatment to many other diseases, including hepatitis C. COVID-19 impacted HCV global elimination efforts with implications not fully comprehended yet. The high genetic variability in HCV makes the development of vaccines and pan-genotypic drug therapies a difficult task. Changes in the dynamics of HCV impose new challenges for public health and opportunities for future research. Meta-analysis, the follow up of new cases and sampling of HCV patients compared with previously available data are options for investigating the possible changes. The determination of HCV genotypes and subtypes is important for understanding viral dynamics and treatment; therefore, the changes in genotype and subtype prevalences can directly affect such processes. Recent results in the literature already suggest changes in HCV dynamics during the COVID-19 pandemic, both considering viral circulation and differential genotypic frequencies in distinct geographic areas. In this context, we propose a further examination of these trends using different approaches to provide support for the hypothesis that the COVID-19 pandemic affected HCV circulation, since these findings would have important implications for hepatitis C prevention, treatment and research. Full article

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children. Full article

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence. Full article

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3–12 years and the first in Europe for adolescents aged 12–17. Full article

Hepatitis C virus (HCV) is a hepatotropic virus that affects millions of human lives worldwide. Direct-acting antiviral (DAA) regimens are the most effective HCV treatment option. However, amino acid substitution-dependent resistance to DAAs has been a major challenge. This study aimed to determine the increasing risk of DAA resistance due to substitutions in DAA target non-structural proteins (NS3/4A, NS5A, and NS5B). Using a Sequence Retrieval System (SRS) at the virus pathogen resource (ViPR/BV-BRC), n = 32763 target protein sequences were retrieved and analyzed for resistance-associated amino acid substitutions (RAASs) by the Sequence Feature Variant Type (SFVT) antiviral-resistance assessment modeling tool. Reference target protein sequences with 100% identity were retried from UniProt following NCBI BLAST. The types and locations of RAASs were identified and visualized by AlphaFold and PyMol. Linux-r-base/R-studio was used for the data presentation. Multi-drug-resistant variants of NS3/4A in genotype 1 (n = 9) and genotype 5 (n = 5) along with DAA-specific NS3/4A, NS5A, and NS5B variants were identified pan-genotypically. A total of 27 variants (RAASs) of all the targets were identified. Fourteen genotype 1-specific substitutions: V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were identified. The most frequent substitutions were V1062L and L2003M, followed by Q2002H. L2003V, Q2002H, M2000T, Y2065N, and NL2003M of NS5A and L2003M of NS5B conferred resistance to daclatasvir. S2702T NS5B was the sofosbuvir-resistant variant. D1194A NS3/4A was triple DAA (simeprevir, faldaprevir, and asunaprevir) resistant. The double-drug resistant variants R1181K (faldaprevir and asunaprevir), A1182V and Q1106K/R (faldaprevir and simeprevir), T1080S (faldaprevir and telaprevir), and single drug-resistant variants V1062L (telaprevir), D1194E/T (simeprevir), D1194G (asunaprevir), S1148A/G (simeprevir), and Q1106L (Boceprevir) of NS3/4A were determined. The molecular phenomenon of DAA resistance is paramount in the development of HCV drug candidates. RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure. Full article