Are earthworms the victim or antidote to antibiotics and antibiotic resistance at the soil-animal-human interface? A One-Health perspective.

The transfer of antibiotics and antibiotic resistance (AR) to the soil systems poses ecological hazards to various organisms, including earthworms. Understanding the complex interactions between earthworms, antibiotics, and AR in the soil system requires a comprehensive assessment. Hence, the present review investigates the behaviour, fate, impacts, and mechanisms involved in the interaction of earthworms with antibiotics and AR. The antibiotics and AR detected in earthworms and their associated media, such as vermicompost, are presented, but several other antibiotics and AR widely detected in soils remain understudied. As receptors and bioassay organisms, earthworms are adversely affected by antibiotics and AR causing (1) acute and chronic toxicity, and (2) emergence of AR in previously susceptible earthworm gut microbiota, respectively. The paper also highlights that, apart from this toxicity, earthworms can also mitigate against antibiotics, antibiotic-resistant bacteria and antibiotic-resistance genes by reducing bacterial diversity and abundance. The behaviour and fate processes, including biodegradation pathways, biomarkers of antibiotics and AR in earthworms, are discussed. In addition, the factors controlling the behaviour and fate of antibiotics and AR and their interactions with earthworms are discussed. Overall, earthworms mitigate antibiotics and AR via various proximal and distal mechanisms, while dual but contradictory functions (i.e., mitigatory and facilitatory) were reported for AR. We recommend that future research based on the One-World-One-Health approach should address the following gaps: (1) under-studied antibiotics and AR, (2) degradation mechanisms and pathways of antibiotics, (3) effects of environmentally relevant mixtures of antibiotics, (4) bio-augmentation in earthworm-based bioremediation of antibiotics, (5) long-term fate of antibiotics and their metabolites, (6) bio-transfers of antibiotics and AR by earthworms, (7) development of earthworm biomarkers for antibiotics and AR, (8) application of earthworm-based bioremediation of antibiotics and AR, (9) cascading ecological impacts of antibiotics and AR on earthworms, and (10) pilot-scale field applications of earthworm-based bioremediation systems.

Correction: Wilanowska et al. Long-Term Survivability of Tardigrade Paramacrobiotus experimentalis (Eutardigrada) at Increased Magnesium Perchlorate Levels: Implications for Astrobiological Research. Life 2024, 14, 335.

There was an error in the original publication [...].

Viral respiratory infections and air pollution: A review focused on research in Poland.

The COVID-19 pandemic has reinforced an interest in the relationship between air pollution and respiratory viral infections, indicating that their burden can be increased under poor air quality. This paper reviews the pathways through which air pollutants can enhance susceptibility to such infections and aggravate their clinical course and outcome. It also summarizes the research exploring the links between various viral infections and exposure to solid and gaseous pollution in Poland, a region characterized by poor air quality, especially during a heating season. The majority of studies focused on concentrations of particulate matter (PM; 86.7%); the other pollutants, i.e., BaP, benzene, CO, NOx, O3, and SO2, were studied less often and sometimes only in the context of a particular infection type. Most research concerned COVID-19, showing that elevated levels of PM and NO2 correlated with higher morbidity and mortality, while increased PM2.5 and benzo[a]pyrene levels were related to worse clinical course and outcome in hospitalized, regardless of age and dominant SARS-CoV-2 variant. PM10 and PM2.5 levels were also associated with the incidence of influenza-like illness and, along with NO2 concentrations, with a higher rate of children's hospitalizations due to lower respiratory tract RSV infections. Higher levels of air pollutants also increased hospitalization due to bronchitis (PM, NOx, and O3) and emergency department admission due to viral croup (PM10, PM2.5, NOx, CO, and benzene). Although the conducted studies imply only correlations and have other limitations, as discussed in the present paper, it appears that improving air quality through reducing combustion processes in energy production in Poland should be perceived as a part of multilayered protection measures against respiratory viral infections, decreasing the healthcare costs of COVID-19, lower tract RSV infections, influenza, and other respiratory viral diseases prevalent between autumn and early spring, in addition to other health and climate benefits.

Influenza vaccination as a prognostic factor of humoral IgA responses to SARS-CoV-2 infection.

There is evidence that influenza vaccination may provide additional benefits by inducing training of innate immunity and increasing humoral responses to heterologous challenges. Immunoglobulin A (IgA) antibodies dominate the early phase of the adaptive response to SARS-CoV-2 infection, but whether their production may be associated with previous influenza vaccination has not been a subject of any study. This study compared serum SARS-CoV-2-specific IgA responses, measured with Microblot-Array assay, in individuals who experienced COVID-19 (N = 1318) and differed in the status of the seasonal influenza vaccine, age, sex, and disease severity. Influenza-vaccinated individuals had a higher seroprevalence of IgA antibodies against nucleocapsid (anti-NP; by 10.1%), receptor-binding domain of spike protein (anti-RBD; by 11.8%) and the S2 subunit of spike protein (anti-S2; by 6.8%). Multivariate analysis, including age, sex, and COVID-19 severity, confirmed that receiving the influenza vaccine was associated with higher odds of being seropositive for anti-NP (OR, 95% CI = 1.57, 1.2-2.0), anti-RBD (OR, 95% CI = 1.6, 1.3-2.0), and anti-S2 (OR, 95% CI = 1.9, 1.4-2.7), as well as being seropositive for at least one anti-SARS-CoV-2 IgA antibody (OR, 95% CI = 1.7, 1.3-2.1) and all three of them (OR, 95% CI = 2.6, 1.7-4.0). Age ≥ 50 years was an additional factor predicting better IgA responses. However, the concentration of particular antibodies in seropositive subjects did not differ in relation to the influenza vaccination status. The study evidenced that influenza vaccination was associated with improved serum IgA levels produced in response to SARS-CoV-2 infection. Further studies are necessary to assess whether trained immunity is involved in the observed phenomenon.

Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals.

INTRODUCTION: With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED: The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION: DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.

Hepatitis C virus (HCV) is an insidious pathogen. Most people infected with HCV will develop chronic infections that may not give any symptoms for years or decades but eventually lead to liver disease and liver cancer. It is essential to diagnose infected individuals as soon as possible and start the treatment to increase the elimination of the virus from the organism and prevent harmful long-term effects.Fortunately, these goals are possible nowadays, and this is due to a remarkable example of translational research at work. The discovery of the virus in 1989 (for which Harvey J. Alter, Michael Houghton, and Charles M. Rice received the Nobel Prize in 2020) was followed by the rapid development of diagnostic tests and later by the introduction of the first interferon therapies, which had numerous shortcomings. The revolution started in 2011 when the first oral drugs that act directly on HCV (direct-acting antivirals, DAAs) were registered. Another giant leap for HCV treatment was made in 2018 when the combinations of DAAs that act on different HCV genotypes were introduced.In this paper, we review in detail the DAAs used to treat HCV infection and explain different combinations in which they can be used while showing their favorable safety profile, short-term and convenient treatment regimen, and impressive effectiveness in clearing HCV infection. Although we believe eliminating HCV is eventually reachable, we also argue that there is room for improvement. HCV testing and DAAs availability must improve in selected groups, including people without health insurance, prisoners, and drug addicts. There are still people living with chronic HCV infection without knowing it. Their identification and start of effective treatment is equal to savings in future medical care related to liver disease and cancer, not to mention benefits from the individual health perspective. In addition, and in line with a popular phrase that prevention is better than cure, it is reasonable to pursue the development of the HCV vaccine, which is currently unavailable. The last word on managing the health burden caused by this pathogen is yet to be said.

The burden of infectious diseases throughout and after the COVID-19 pandemic (2020-2023) and Russo-Ukrainian war migration.

Understanding how the infectious disease burden was affected throughout the COVID-19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID-19 pandemic and after the influx of war refugees from Ukraine. We performed a registry-based population-wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016-2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS-CoV-2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick-borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two-fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID-19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID-19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future.

Humoral anti-SARS-CoV-2 response in patients with different long COVID phenotypes.

Long COVID (LC) is characterized by persistent symptoms following SARS-CoV-2 infection, with various mechanisms offered to explain its pathogenesis. This study explored whether adaptive humoral anti-SARS-CoV-2 responses differ in LC. Unvaccinated COVID-19 convalescents (n = 200) were enrolled, with 21.5% (n = 43) presenting LC three months post-infection. LC diagnosis was based on persistent symptom(s) and alterations in biochemical/clinical markers; three phenotypes were distinguished: cardiological, pulmonary, and psychiatric LC. All three phenotypes were characterized by significantly decreased seroprevalence of IgG antibodies against nucleocapsid (anti-NP). LC was associated with decreased odds of testing positive for anti-NP (OR = 0.35, 95%CI: 0.16-0.78, p = 0.001). Seropositive LC patients had lower anti-S1 and anti-S2 levels than individuals without LC, and those with pulmonary and psychological phenotypes also revealed decreased anti-RBD concentrations. The results indicate that LC can be characterized by diminished humoral response to SARS-CoV-2. The potential implication of this phenomenon in post-acute viral sequelae is discussed.

Illicit Drugs in Surface Waters: How to Get Fish off the Addictive Hook.

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the environmental aspects of their use and subsequent emissions usually remain less explored. However, as with other human activities, drug production, trade, and consumption of drugs may leave their environmental mark. Therefore, this paper aims to review the occurrence of illicit drugs in surface waters and their bioaccumulation and toxicity in fish. Illicit drugs of different groups, i.e., psychostimulants (methamphetamines/amphetamines, cocaine, and its metabolite benzoylecgonine) and depressants (opioids: morphine, heroin, methadone, fentanyl), can reach the aquatic environment through wastewater discharge as they are often not entirely removed during wastewater treatment processes, resulting in their subsequent circulation in nanomolar concentrations, potentially affecting aquatic biota, including fish. Exposure to such xenobiotics can induce oxidative stress and dysfunction to mitochondrial and lysosomal function, distort locomotion activity by regulating the dopaminergic and glutamatergic systems, increase the predation risk, instigate neurological disorders, disbalance neurotransmission, and produce histopathological alterations in the brain and liver tissues, similar to those described in mammals. Hence, this drugs-related multidimensional harm to fish should be thoroughly investigated in line with environmental protection policies before it is too late. At the same time, selected fish species (e.g., Danio rerio, zebrafish) can be employed as models to study toxic and binge-like effects of psychoactive, illicit compounds.

Long-Term Survivability of Tardigrade Paramacrobiotus experimentalis (Eutardigrada) at Increased Magnesium Perchlorate Levels: Implications for Astrobiological Research.

Perchlorate salts, including magnesium perchlorate, are highly toxic compounds that occur on Mars at levels far surpassing those on Earth and pose a significant challenge to the survival of life on this planet. Tardigrades are commonly known for their extraordinary resistance to extreme environmental conditions and are considered model organisms for space and astrobiological research. However, their long-term tolerance to perchlorate salts has not been the subject of any previous studies. Therefore, the present study aimed to assess whether the tardigrade species Paramacrobiotus experimentalis can survive and grow in an environment contaminated with high levels of magnesium perchlorates (0.25-1.0%, 1.5-6.0 mM ClO4- ions). The survival rate of tardigrades decreased with an increase in the concentration of the perchlorate solutions and varied from 83.3% (0.10% concentration) to 20.8% (0.25% concentration) over the course of 56 days of exposure. Tardigrades exposed to 0.15-0.25% magnesium perchlorate revealed significantly decreased body length. Our study indicates that tardigrades can survive and grow in relatively high concentrations of magnesium perchlorates, largely exceeding perchlorate levels observed naturally on Earth, indicating their potential use in Martian experiments.

Trends of Hepatitis A Virus Infection in Poland: Assessing the Potential Impact of the COVID-19 Pandemic and War in Ukraine.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis, which is preventable by vaccination. This study analyzed trends of HAV infections in Poland according to socio-demographic features in the years 2009-2022 and assessed the potential impact of the COVID-19 pandemic (2020-2023) and the migration of war refugees from Ukraine (since February 2022). In 2009-2022, 7115 new cases of HAV infection were diagnosed in Poland, especially among men (66.4%) and in urban areas (77.4%). Infections among men were most common at the age of 25-34 (median rate 0.43 per 105) and in women aged 15-24 (median rate 0.39 per 105). Analysis of the 14-year frequency of HAV infections exhibited three trends, regardless of gender, age, and residence. The infections revealed a downward trend in 2009-2014, increased significantly in 2014-2018, and decreased again after 2018. A particularly rapid increase in HAV infections occurred between March 2017 and February 2018 (median rate 0.79 per 105). The high level of new infections persisted until the beginning of the COVID-19 pandemic, at which point it dropped significantly but did not reach the level recorded before March 2017. During the Omicron SARS-CoV-2 dominance period, the median rate of HAV infections was 0.053 per 105, with a four-fold increase being observed from February 2022 (when the migration of war refugees from Ukraine began) to August 2022. The presented results can serve as a reference point for further observations in Central Europe. The HAV epidemiological situation is unlikely to escalate in Poland but requires further monitoring.

Direct-acting antivirals in women of reproductive age infected with hepatitis C virus.

Eliminating hepatitis C virus (HCV) infection in the population of women of reproductive age is important not only for the health of women themselves but also for the health of newborns. This study aimed to evaluate the implementation of this goal by analysing the effectiveness of contemporary therapy in a large cohort from everyday clinical practice along with identifying factors reducing therapeutic success. The analysed population consisted of 7861 patients, including 3388 women aged 15-49, treated in 2015-2022 in 26 hepatology centres. Data were collected retrospectively using a nationwide EpiTer-2 database. Females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs. 15.7%) and less frequently showed comorbidities (40.5% vs. 44.2%) and comedications (37.2% vs. 45.2%). Hepatocellular carcinoma, liver transplantation, HIV and HBV coinfections were reported significantly less frequently in women. Regardless of the treatment type, females significantly more often reached sustained virologic response (98.8%) compared to males (96.8%). Regardless of gender, genotype 3 and cirrhosis were independent factors increasing the risk of treatment failure. Women more commonly reported adverse events, but death occurred significantly more frequently in men (0.3% vs. 0.1%), usually related to underlying advanced liver disease. We have demonstrated excellent effectiveness and safety profiles for treating HCV infection in women. This gives hope for the micro-elimination of HCV infections in women, translating into a reduced risk of severe disease in both women and their children.

Climate warming, environmental degradation and pollution as drivers of antibiotic resistance.

Antibiotic resistance is a major challenge to public health, but human-caused environmental changes have not been widely recognized as its drivers. Here, we provide a comprehensive overview of the relationships between environmental degradation and antibiotic resistance, demonstrating that the former can potentially fuel the latter with significant public health outcomes. We describe that (i) global warming favors horizontal gene transfer, bacterial infections, the spread of drug-resistant pathogens due to water scarcity, and the release of resistance genes with wastewater; (ii) pesticide and metal pollution act as co-selectors of antibiotic resistance mechanisms; (iii) microplastics create conditions promoting and spreading antibiotic resistance and resistant bacteria; (iv) changes in land use, deforestation, and environmental pollution reduce microbial diversity, a natural barrier to antibiotic resistance spread. We argue that management of antibiotic resistance must integrate environmental goals, including mitigation of further increases in the Earth's surface temperature, better qualitative and quantitative protection of water resources, strengthening of sewage infrastructure and improving wastewater treatment, counteracting the microbial diversity loss, reduction of pesticide and metal emissions, and plastic use, and improving waste recycling. These actions should be accompanied by restricting antibiotic use only to clinically justified situations, developing novel treatments, and promoting prophylaxis. It is pivotal for health authorities and the medical community to adopt the protection of environmental quality as a part of public health measures, also in the context of antibiotic resistance management.

Respiratory syncytial virus immunoprophylaxis: Novel opportunities and a call for equity.

With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low-to-middle-income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti-RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower-income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden.

Hepatitis B virus coinfection in patients treated for chronic hepatitis C: clinical characteristics, risk of reactivation with long-term follow-up, and effectiveness of antiviral therapy.

INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share a similar transmission route, which increases coinfection odds and worsens clinical outcomes. OBJECTIVES: Our aim was to investigate coinfected patients undergoing HCV treatment with direct-acting antivirals (DAAs) to understand their characteristics, risk of HBV reactivation, and effectiveness of the therapy. PATIENTS AND METHODS: Our study comprehensively analyzed 1118 patients with chronic HCV infection, divided into 3 subgroups based on their HBV status. RESULTS: We documented that 0.7% of the analyzed population was positive for hepatitis B virus surface antigen (HBsAg), while 14.3% had evidence of a past HBV infection. The patients without HBV coinfection were less burdened with comorbidities, and were mostly treatment-naive, while the individuals suffering from coinfection were younger and more likely to have a history of a previous therapy. Infection with HCV genotype 3 was more common among the HBsAg-positive patients than in the other studied groups. Response to DAA therapy was comparable between the groups, and most patients completed the course of treatment as planned. Only 3 cases of HBV reactivation were observed, all of which achieved sustained virologic response after DAA therapy. Two were women on immunosuppressants with antihepatitis B core positive antibodies, and the third patient was an HBsAgpositive man. These patients remained in long-term follow-up. CONCLUSIONS: Neither the presence of HBV markers nor HBV reactivation during DAA treatment reduced effectiveness of the therapy. Our findings are important for future recommendations and guidelines on managing HBV/HCV coinfection.

In Vitro Evidence of Selective Pro-Apoptotic Action of the Pure Cannabidiol and Cannabidiol-Rich Extract.

Plant cannabinoids, secondary metabolites of species belonging to the Cannabis genus, can mimic the endocannabinoids' action and exert biological effects. Considering the contribution of the endocannabinoid system in cell cycle and apoptotic regulation, there is an interest in exploring the potential anti-cancer activities of natural and synthetic cannabinoids. Cannabidiol (CBD), an abundant plant cannabinoid, reveals a low affinity to cannabinoid receptors and, contrary to various cannabinoids, lacks psychoactive action. Here, we present the in vitro assessment of the pro-apoptototic potential of CBD-rich extracts of Cannabis sativa L. (eCBD) compared to purified CBD (pCBD). As demonstrated, both eCBD and pCBD decreased the viability of breast cancer cell line MDA-MB-231 and human prostate cancer cell line PC-3 in a concentration-dependent fashion. Endoplasmic reticulum stress-related apoptosis and morphological changes were induced only in low-serum conditions. Moreover, the effects of eCDB and pCDB were also assessed in non-malignant cell lines (MCF-10A and PNT2) with no alterations of viability noted, ultimately suggesting a selective action of CBD in tumor cells. The results suggest the possible involvement of reactive oxygen species in the response mechanism to eCBD and pCBD, but no clear pattern was observed. We also demonstrated significant changes in gene expression involved in apoptosis and cell cycle control upon extract treatment. Altogether, our study shows the potential of eCBD and pCBD as novel pro-apoptototic agents that can be considered promising in future preclinical and clinical testing.

Gene-Editing and RNA Interference in Treating Hepatitis B: A Review.

The hepatitis B virus (HBV) continues to cause substantial health and economic burdens, and its target of elimination may not be reached in 2030 without further efforts in diagnostics, non-pharmaceutical prevention measures, vaccination, and treatment. Current therapeutic options in chronic HBV, based on interferons and/or nucleos(t)ide analogs, suppress the virus replication but do not eliminate the pathogen and suffer from several constraints. This paper reviews the progress on biotechnological approaches in functional and definitive HBV treatments, including gene-editing tools, i.e., zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9, as well as therapeutics based on RNA interference. The advantages and challenges of these approaches are also discussed. Although the safety and efficacy of gene-editing tools in HBV therapies are yet to be demonstrated, they show promise for the revitalization of a much-needed advance in the field and offer viral eradication. Particular hopes are related to CRISPR/Cas9; however, therapeutics employing this system are yet to enter the clinical testing phases. In contrast, a number of candidates based on RNA interference, intending to confer a functional cure, have already been introduced to human studies. However, larger and longer trials are required to assess their efficacy and safety. Considering that prevention is always superior to treatment, it is essential to pursue global efforts in HBV vaccination.

Does a detectable HCV RNA at the end of DAA therapy herald treatment failure?

BACKGROUND & AIMS: The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET. METHODS: The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015-2023. RESULTS: Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders. CONCLUSIONS: We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders.