Patient with actinomycosis of the cervicofacial and abdominal area, case report. / Wielopostaciowosc promienicy ­ jednoczesna aktynomikoza obszaru szyjno-twarzowego i brzusznego, opis przypadku.

Actinomycosis is a very rare, infectious disease, which is especially difficult to diagnose due to non-specific symptoms and the ability to emulate neoplasms or inflammatory changes. Due to those facts, it is often misdiagnosed or diagnosed too late to be successfully treated. This article presents the case of 31-year-old Caucasian female with recurrent upper respiratory tract infections and tonsillitis as the potential risk factors of actinomycosis. Upon examination of material collected through the course of tonsillectomy, the patient was diagnosed with actinomycosis of the left palatine tonsil. Despite the introduction of antibiotic therapy, initial progression was noted with the appearance of numerous, hypodense changes in the liver and the spleen, which regressed during further antibiotic treatment. According to our team's knowledge, this is the first described case of a patient with actinomycosis occurring simultaneously in the cervico-facial and abdominal area. The unusual localization and potential dissemination of actinomycosis should be considered in clinical practice.

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.

Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Post-Acute COVID-19 Syndrome.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is part of the innate immune system and acute-phase protein. Current data state that acute COVID-19 patients have higher levels of serum NGAL (sNGAL), but it is not known if higher protein levels are maintained in the convalescents. As post-COVID complications are currently the most important aspect of the disease, further research into metabolic and immunological consequences of the disease is needed. Methods: We aimed to determine the levels of sNGAL in a patient population 3 months after the acute phase of the disease and to identify the factors that may be related to the elevation of sNGAL levels in the mentioned cohort. The study included 146 patients diagnosed with COVID-19 in different stages of the disease. Three months after COVID-19 diagnosis, patients' sera were sampled and tested. Results: We demonstrate an association between the severity of the disease in the acute phase and elevated sNGAL levels three months after recovery, with the exception of the most severe hospitalized patients, who received early treatment. Moreover, we establish that sNGAL levels could be associated with prolonged dyspnea and the regulation of hunger and satiety in COVID-19 convalescents. Conclusions: These observations support the view that the introduction of antiviral treatment, steroids, and intense oxygen therapy reduces post-COVID immune-associated complications.

Effectiveness and safety of direct-acting antivirals in the therapy of HCV-infected elderly people.

BACKGROUND: The introduction of direct-acting antivirals (DAAs) with their effectiveness and safety has revolutionized the approach to treating hepatitis C virus (HCV) infections. Nevertheless, elderly patients have often been excluded from clinical trials, so the results of real-world studies are particularly important in the context of the geriatric population. The study aimed to analyze the effectiveness and safety of antiviral DAA treatment in HCV-infected patients over the age of 65, with notable inclusion of those over the age of 85. METHODS: The analyzed patients were divided by age into three groups: group A (65-74 years), group B (75-84 years) and group C (85 years or older). Patients started DAA based therapy at 22 hepatology centers between July 2015 and December 2022. RESULTS: A total of 3505 elderly patients were included in the analysis, and this group consisted of 2501 patients in group A, 893 in group B, and 111 in group C. The study population, regardless of age, was dominated by women. Patients had a high prevalence of comorbidities (84.9%, 92.2%, and 93.7%, respectively) as well as a high rate of concomitant medications. The sustained virological response was 97.9% in groups A and B and 100% in group C. The therapy was well-tolerated, with a comparable safety profile observed in all analyzed groups. CONCLUSIONS: DAA-based therapies are highly effective and well tolerated by the elderly patients, including those over 85. Age should not be a barrier to treatment, but careful management is necessary.

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.

Kinetics and Value of Hepatitis B Core-Related Antigen in Patients with Chronic Hepatitis B Virus Infection during Antiviral Treatment.

BACKGROUND: The hepatitis B core-related antigen (HBcrAg) correlates with HBV DNA in patients with chronic HBV infection without antiviral treatment. Its utility in monitoring patients during and after the cessation of nucleos(t)ide analog (NA) treatment is unknown. METHODS: The levels of HBcrAg were longitudinally determined in two cohorts of chronic HBV-infected patients with (A) newly started NA treatment or (B) after NA cessation during a median follow up (FU) of 60 months or 48 weeks, respectively. The correlation of HBcrAg and HBV DNA and the predictive value for HBeAg seroconversion and HBsAg loss were evaluated. RESULTS: Fifty-six patients with newly-started NA treatment and 22 patients with NA cessation were identified. HBcrAg and HBV DNA strongly correlated before NA treatment (r = 0.77, p < 0.0001) and at virological relapse (0.66, p = 0.0063). At the individual level, the discrepant kinetics of HBcrAg and HBV DNA became evident. During NA treatment, 33% (6/18) and 9% (5/56) of patients showed HBeAg seroconversion or HBsAg loss/HBsAg < 100 IU/mL, respectively. Low levels of HBcrAg were associated with these endpoints. CONCLUSION: HBcrAg levels before antiviral treatment help to identify patients with chances of HBsAg loss or HBeAg seroconversion. However, its utility in replacing quantitative HBV DNA to evaluate treatment efficacy or virological relapse off-treatment is limited.

Treatment of the most difficult-to-cure hepatitis C virus-infected population with sofosbuvir / velpatasvir.

INTRODUCTION: Pangenotypic therapies for infections with hepatitis C virus (HCV), although universal and highly effective, entail a risk of treatment failure. OBJECTIVES: Our study aimed to identify the population of HCV­infected patients most difficult to cure with the sofosbuvir / velpatasvir (SOF/VEL) regimen. PATIENTS AND METHODS: The effectiveness of the SOF/VEL regimen with a possible addition of ribavirin (RBV) was evaluated in populations known to be less responsive to treatment, and then in a population characterized by the combination of all factors impairing effectiveness, comprising patients treated with this regimen in the EpiTer­2 multicenter retrospective study. RESULTS: A total of 2267 patients were treated with SOF/VEL±RBV. Of those, 2078 (96.4%) achieved sustained virologic response. The cure rate was 93.5% among 646 patients infected with genotype (GT) 3, 92.3% among 635 patients with cirrhosis, 95.5% in a population of 1233 men, and 94.1% among 421 patients with body mass index (BMI) above 30. An analysis in a group of 43 men with cirrhosis and obesity infected with GT3 showed the effectiveness of pangenotypic therapy at only 79.1%, falling to 66.7% in individuals with previous treatment failure. CONCLUSIONS: In a large population of SOF/VEL­treated HCV­infected patients, we showed relatively low effectiveness of the regimen in treatment­experienced men with cirrhosis and obesity, infected with GT3. Triple therapy should be considered when initiating the treatment of HCV infections in this group, which, however, needs to be confirmed in further studies. Previous studies were conducted in less demanding populations, because they did not take into account sex and BMI, which significantly affect the treatment effectiveness.

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.

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals.

Aim of the study: Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. Material and methods: The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. Results: The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. Conclusions: A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

Change in the Clinical Picture of Hospitalized Patients with COVID-19 between the Early and Late Period of Dominance of the Omicron SARS-CoV-2 Variant.

This study aimed to compare the clinical picture of COVID-19 in the initial and later period of Omicron dominance and to identify populations still at risk. A retrospective comparison of the clinical data of 965 patients hospitalized during the early period of Omicron's dominance (EO, January-June 2022) with 897 patients from a later period (LO, July 2022-April 2023) from the SARSTer database was performed. Patients hospitalized during LO, compared to EO, were older, had a better clinical condition on admission, had a lower need for oxygen and mechanical ventilation, had less frequent lung involvement in imaging, and showed much faster clinical improvement. Moreover, the overall mortality during EO was 14%, higher than that in LO-9%. Despite the milder course of the disease, mortality exceeding 15% was similar in both groups among patients with lung involvement. The accumulation of risk factors such as an age of 60+, comorbidities, lung involvement, and oxygen saturation <90% resulted in a constant need for oxygen in 98% of patients, an 8% risk of mechanical ventilation, and a 30% mortality rate in the LO period. Multiple logistic regression revealed lower odds of death during the LO phase. Despite the milder course of infections caused by the currently dominant subvariants, COVID-19 prophylaxis is necessary in people over 60 years of age, especially those with comorbidities, and in the case of pneumonia and respiratory failure.

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

OCRELIZUMAB THERAPY IN PATIENTS WITH ANTI-HBC ANTIBODIES - A PRELIMINARY STUDY.

OBJECTIVE: Aim: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease resulting in cognitive impairment, physical disabilities, and neurological symptoms. Ocrelizumab is an effective drug used in MS treatment. However, it causes a risk of hepatitis B reactivation in anti-HBc positive patients. We describe the impact of entecavir and tenofovir on HBV reactivation during treatment with ocrelizumab. PATIENTS AND METHODS: Materials and methods: Our study included eight patients (aged 18-70 years) with positive anti-HBc antibodies who were diagnosed with MS based on the 2017 McDonald criteria. The subjects were treated with ocrelizumab and were given anti-HBV prophylaxis with nucleoside analogs. The mean time from the beginning of therapy with nucleoside analogs to the initiation of ocrelizumab treatment was 27.5 days. Patients were administered ocrelizumab and none of them was diagnosed with HBV reactivation. RESULTS: Results: None of the laboratory parameters worsened. No severe adverse effects were observed. These results suggest that entecavir and tenofovir are effective in HBV reactivation prophylaxis. Additionally, positive anti-HBc antibodies do not rule out treatment with ocrelizumab. CONCLUSION: Conclusions: In patients with positive anti-HBc antibodies, nucleoside analogs, such as entecavir or tenofovir, should be administered before ocrelizumab administration to reduce the risk of viral reactivation. Further studies on simultaneous treatment with ocrelizumab and nucleoside analogs are required to confirm our findings.

Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 µm (PM10 ) and <2.5 µm (PM2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to  d-dimer >2 mg/L and fatal outcome. Elevated PM10 and PM2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance.

Real-World Effectiveness and Safety of Direct-Acting Antivirals in Patients with Chronic Hepatitis C and Epilepsy: An Epi-Ter-2 Study in Poland.

INTRODUCTION: In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy. METHODS: A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective. RESULTS: The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy. CONCLUSIONS: The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

Overview of autoantibodies in COVID-19 convalescents.

Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.

Pathological changes or technical artefacts? The problem of the heterogenous databases in COVID-19 CXR image analysis.

BACKGROUND: When the COVID-19 pandemic commenced in 2020, scientists assisted medical specialists with diagnostic algorithm development. One scientific research area related to COVID-19 diagnosis was medical imaging and its potential to support molecular tests. Unfortunately, several systems reported high accuracy in development but did not fare well in clinical application. The reason was poor generalization, a long-standing issue in AI development. Researchers found many causes of this issue and decided to refer to them as confounders, meaning a set of artefacts and methodological errors associated with the method. We aim to contribute to this steed by highlighting an undiscussed confounder related to image resolution. METHODS: 20 216 chest X-ray images (CXR) from worldwide centres were analyzed. The CXRs were bijectively projected into the 2D domain by performing Uniform Manifold Approximation and Projection (UMAP) embedding on the radiomic features (rUMAP) or CNN-based neural features (nUMAP) from the pre-last layer of the pre-trained classification neural network. Additional 44 339 thorax CXRs were used for validation. The comprehensive analysis of the multimodality of the density distribution in rUMAP/nUMAP domains and its relation to the original image properties was used to identify the main confounders. RESULTS: nUMAP revealed a hidden bias of neural networks towards the image resolution, which the regular up-sampling procedure cannot compensate for. The issue appears regardless of the network architecture and is not observed in a high-resolution dataset. The impact of the resolution heterogeneity can be partially diminished by applying advanced deep-learning-based super-resolution networks. CONCLUSIONS: rUMAP and nUMAP are great tools for image homogeneity analysis and bias discovery, as demonstrated by applying them to COVID-19 image data. Nonetheless, nUMAP could be applied to any type of data for which a deep neural network could be constructed. Advanced image super-resolution solutions are needed to reduce the impact of the resolution diversity on the classification network decision.

Recommendations of the Polish Group of Experts for HCV for the treatment of hepatitis C in 2023.

The recommendations define the principles of diagnosis and treatment of hepatitis C virus (HCV) infection according to the latest knowledge. The main goal of the treatment of HCV infection is to eliminate the virus from the body, which in turn leads to stopping the progression or causes the regression of previously formed changes in the liver. The current version of the guidelines prioritizes pangenotypic regimens and includes guidelines for special patient populations such as children, patients with cirrhosis, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection, patients with renal failure, liver failure and lack of response to previous therapies as well as patients in the peri-transplant period.

Retrospective Analysis of the Effectiveness of Remdesivir in COVID-19 Treatment during Periods Dominated by Delta and Omicron SARS-CoV-2 Variants in Clinical Settings.

Continuous evaluation of real-world treatment effectiveness of COVID-19 medicines is required due to the ongoing evolution of SARS-CoV-2 and the possible emergence of resistance. Therefore, this study aimed to analyze, in a retrospective manner, the outcomes in patients hospitalized with COVID-19 during the pandemic waves dominated by Delta and Omicron variants and treated with remdesivir (RDV) (n = 762) in comparison to a demographically and clinically matched group not treated with any antivirals (n = 1060). A logistic regression analysis revealed that RDV treatment was associated with a significantly lower risk of death during both Delta wave (OR = 0.42, 95%CI: 0.29-0.60; p < 0.0001) and Omicron-dominated period (OR = 0.56, 95%CI: 0.35-0.92; p = 0.02). Moreover, RDV-treated groups were characterized by a lower percentage of patients requiring mechanical ventilation, but the difference was not statistically significant. This study is the first real-world evidence that RDV remains effective during the dominance of more pathogenic SARS-CoV-2 variants and those that cause a milder course of the disease, and continues to be an essential element of COVID-19 therapy.

Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens.

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.