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The 2'-O-methylation (2'-O-Me) of ribosomal RNA (rRNA) shows plasticity that is potentially associated with cell phenotypes. We used RiboMeth-seq profiling to reveal growth arrest-specific 2'-O-Me patterns in primary human dermal fibroblasts from three different donors. We exposed cells to hydrogen peroxide to induce cellular senescence and to high cell densities to promote quiescence by contact inhibition. We compared both modes of cell cycle arrest to proliferating cells and could indeed distinguish these conditions by their overall 2'-O-Me patterns. Methylation levels at a small fraction of sites showed plasticity and correlated with the expression of specific small nucleolar RNAs (snoRNAs) but not with expression of fibrillarin. Moreover, we observed subtle senescence-associated alterations in ribosome biogenesis. Knockdown of the snoRNA SNORD87, which acts as a guide for modification of a hypermethylated position in non-proliferating cells, was sufficient to boost cell proliferation. Conversely, depletion of SNORD88A, SNORD88B and SNORD88C, which act as guides for modification of a hypomethylated site, caused decreased proliferation without affecting global protein synthesis or apoptosis. Taken together, our findings provide evidence that rRNA modifications can be used to distinguish and potentially influence specific growth phenotypes of primary cells.
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RNA Ribossômico , Ribose , Humanos , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribose/metabolismo , Ribossomos/metabolismo , Metilação , RNA Nucleolar Pequeno/genética , Fibroblastos/metabolismoRESUMO
A growing body of research suggests that emotional chemosignals in others' body odor (BO), particularly those sampled during fearful states, enhance emotional face perception in conscious and preconscious stages. For instance, emotional faces access visual awareness faster when presented with others' fear BOs. However, the effect of these emotional signals in self-BO, that is, one's own BO, is still neglected in the literature. In the present work, we sought to determine whether emotional self-BOs modify the access to visual awareness of emotional faces. Thirty-eight women underwent a breaking-Continuous Flash Suppression task in which they were asked to detect fearful, happy, and neutral faces, as quickly and accurately as possible, while being exposed to their fear, happiness, and neutral self-BOs. Self-BOs were previously collected and later delivered via an olfactometer, using an event-related design. Results showed a main effect of emotional faces, with happy faces being detected significantly faster than fearful and neutral faces. However, our hypothesis that fear self-BOs would lead to faster emotional face detection was not confirmed, as no effect of emotional self-BOs was found-this was confirmed with Bayesian analysis. Although caution is warranted when interpreting these results, our findings suggest that emotional face perception is not modulated by emotional self-BOs, contrasting with the literature on others' BOs. Further research is needed to understand the role of self-BOs in visual processing and emotion perception.
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Odor Corporal , Expressão Facial , Humanos , Feminino , Teorema de Bayes , Emoções , MedoRESUMO
Facial emotional expressions are pivotal for social communication. Their fast and accurate recognition is crucial to promote adaptive responses to social demands, for the development of functional relationships, and for well-being. However, the literature has been inconsistent in showing differentiated recognition patterns for positive vs. negative facial expressions (e.g., happy and angry expressions, respectively), likely due to affective and perceptual factors. Accordingly, the present study explored differences in recognition performance between angry and happy faces, while specifically assessing the role of emotional intensity and global/regional low-level visual features. 98 participants categorized angry and happy faces morphed between neutral and emotional across 9 levels of expression intensity (10-90%). We observed a significantly higher recognition efficiency (higher accuracy and shorter response latencies) for angry compared to happy faces in lower levels of expression intensity, suggesting that our cognitive resources are biased to prioritize the recognition of potentially harmful stimuli, especially when briefly presented at an ambiguous stage of expression. Conversely, an advantage for happy faces was observed from the midpoint of expression intensity, regarding response speed. However, when compensating for the contribution of regional low-level properties of distinct facial key regions, the effect of emotion was maintained only for response accuracy. Altogether, these results shed new light on the processing of facial emotional stimuli, emphasizing the need to consider emotional intensity and regional low-level image properties in emotion recognition analysis.
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Ira , Emoções , Humanos , Emoções/fisiologia , Ira/fisiologia , Felicidade , Reconhecimento Psicológico , Tempo de Reação , Expressão FacialRESUMO
A 68-year-old overweight woman with no history of oral contraceptive use presented a large liver mass of 40 cm on abdominal ultrasound without associated symptoms. Complete blood count, coagulation study, and liver biochemistry were unremarkable. Abdominal contrast-enhanced CT revealed a 33x24 cm lesion with discontinuous peripheral globular uptake and centripetal fill-in, consistent with an extremely giant hemangioma. It affected all segments of the right lobe, compressing the right suprahepatic vein and displacing all intra-abdominal structures, with a deviation of the midline structures (stomach and pancreas) to the left. Given the hemangioma size and its significant mass effect, surgery was discussed but declined by the patient, who remains asymptomatic 3 years later. Extremely giant liver hemangiomas (>10 cm) are rare, and the approach to asymptomatic patients is debated. Some advocate for prophylactic excision due to the potential for internal bleeding, growth, or rupture, while others suggest intervention for hemangiomas near major vascular structures. The American College of Gastroenterology recommends surgical intervention in such cases, but the European Association for the Study of the Liver suggests a conservative approach for most patients. This case highlights a successful "watch-and-wait" strategy, bringing attention to this unusual condition and its controversial management.
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Fishing is one of the most widespread and important human activities in coastal ecosystems and it plays a fundamental role in employment and the economy of coastal communities. However, in the period 2020-2021, the global outbreak of COVID-19 negatively affected fishing economic activity. Against this background, Andalusia (South of Spain) is an important region in which the resilience of different fishing exploitation systems can be studied, but within the same social and economic framework. Therefore, the main study aim was to investigate the resilience of fishing activity to the COVID-19 pandemic in two Andalusian fishing grounds (i.e. Atlantic and Mediterranean). We analysed daily landings and the first-sale prices of fresh fish of the most caught species in both fishing grounds, while taking into account the different seasonal behaviour of the fisheries. Generalised Linear Models were used to compare the data, which were obtained during periods in which the COVID-19 severity levels differed. These levels were implemented according to political measures. The final objective was to understand how the degree of industrialisation in the fleets can hinder or help maintain the economic activity of fisheries during major crises.
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INTRODUCTION: Gender differences in sexual responses and cognitive and emotional processing to romantic and sexually explicit stimuli have been reported. However, these differences seem to depend on the automaticity of the task that is being used, thus suggesting that gender differences may be the result of specific mechanisms rather than a generalized effect. AIM: To expand previous basic processes research on gender differences to romantic vs sexually explicit stimuli, focusing on potential differentiating mechanisms influencing male and female sexual responses, we aim to investigate gender differences on automatic attention to sexual stimuli, and to test its relationship with sexual excitation proneness. METHODS: 26 women and 30 men (heterosexual) performed an automatic attention task, in which romantic and sexually explicit stimuli were presented as distractors, that is, stimuli to be ignored, while a concurrent letter discrimination task was performed, followed by a self-report task assessing subjective sexual and emotional responses to the stimuli. MAIN OUTCOME MEASURES: Percentage of accuracy and response times (RTs) to discriminate the target letters were used as markers of automatic attention, with lower accuracy and longer RTs reflecting a higher degree of attentional capture by the distractor stimuli (romantic and sexually explicit). Participants completed self-report ratings on emotional valence, general arousal, and sexual arousal toward romantic and sexually explicit stimuli. They further reported on their sexual excitation proneness. RESULTS: Findings revealed that sexually explicit pictures yielded more automatic attention capture. However, this effect was superseded by pornography consumption, which likely reflects a habituation mechanism. Also, data revealed gender-x type of picture interaction effects only at the self-report task, with men rating sexually explicit stimuli as more sexually exciting, and women rating these stimuli as less pleasant. No relationship was found between automatic attention proxies and sexual excitation proneness. CLINICAL TRANSLATION: While therapeutic strategies are used as tools to improve attention to sexual stimuli (and, hence, increase sexual arousal), the current findings suggest that the specific pathways by which attention influences sexual response are still to be established. Also, gender differences on the subjective appraisal of sex stimuli suggest that therapeutic approaches, consisting on exposure techniques, must recognize gender specificities. STRENGTHS & LIMITATIONS: To our knowledge, this is the first study applying an automatic attention task to the field of sex research, thus adding new inputs to the topic of attention, gender differences, and sexual response. However, there is very limited research in the field of automatic attention, which may limit the interpretation of our findings, at the moment. CONCLUSION: Whereas both genders do not seem to differ in automatic attention toward romantic and sexually explicit stimuli, their responses do differ in their subjective appraisal of the stimuli. Furthermore, despite theoretical assumptions on the relationship between attention and sexual response, automatic attention seemed not to be related to sexual excitation proneness. Carvalho J, Czop O, Rocha M, et al. Gender differences in the automatic attention to romantic vs sexually explicit stimuli. J Sex Med 2018;15:1083-1092.
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Emoções/fisiologia , Literatura Erótica/psicologia , Heterossexualidade/psicologia , Fatores Sexuais , Adulto , Atenção/fisiologia , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Fatores de Tempo , Adulto JovemRESUMO
Body odors (BOs) can convey social information. In particular, their effects are maximal when their presence is paired with meaningful social contexts. Static faces have been widely used as social stimuli. However, they miss a key feature of our phenomenological experience, characterized by multisensory dynamic stimulations. Here, we investigate how BO sampled from individuals experiencing a transitory anxiety state, (a) induce a stress response and (b) bias the recognition of dynamic facial expressions, compared with BO of relaxed individuals. Participants ( n=46) categorized the emotion of a face, morphing from a neutral expression to either an angry or happy expression, during exposure to either BO condition. In addition, their cardiac activity was measured. Exposure to anxiety BO increased the accuracy of dynamic facial recognition and reduced cardiac parasympathetic activity. These results suggest that in social situations that simulate part of the multisensory and dynamic features of real-life social contexts, anxiety BOs will induce a stress response in recipients, modulating both arousal and cognitive-emotional skills but facilitating emotional facial processing.
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Ansiedade/fisiopatologia , Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Frequência Cardíaca/fisiologia , Percepção Olfatória/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Percepção Social , Estresse Psicológico/fisiopatologia , Adulto , Feminino , Humanos , Odorantes , Adulto JovemRESUMO
Conditions during information encoding and retrieval are known to influence the sensory material stored and its recapitulation. However, little is known about such processes in olfaction. Here, we capitalized on the uniqueness of body odors (BOs) which, similar to fingerprints, allow for the identification of a specific person, by associating their presentation to a negative or a neutral emotional context. One hundred twenty-five receivers (68 F) were exposed to a male BO while watching either criminal or neutral videos (encoding phase) and were subsequently asked to recognize the target BO within either a congruent or an incongruent visual context (retrieval phase). The results showed that criminal videos were rated as more vivid, unpleasant, and arousing than neutral videos both at encoding and retrieval. Moreover, in terms of BO ratings, we found that odor intensity and arousal allow to distinguish the target from the foils when congruent criminal information is presented at encoding and retrieval. Finally, the accuracy performance was not significantly different from chance level for either condition. These findings provide insights on how olfactory memories are processed in emotional situations.
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Emoções , Memória , Rememoração Mental , Odorantes , Percepção Olfatória , Adolescente , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Percepção Visual , Adulto JovemRESUMO
The Mediterranean region is projected to be extremely vulnerable to global change, which will affect the distribution of typical forest types such as native oak forests. However, our understanding of Mediterranean oak forest responses to future conditions is still very limited by the lack of knowledge on oak forest dynamics and species-specific responses to multiple drivers. We compared the long-term (1966-2006) forest persistence and land cover change among evergreen (cork oak and holm oak) and deciduous oak forests and evaluated the importance of anthropogenic and environmental drivers on observed changes for Portugal. We used National Forest Inventories to quantify the changes in oak forests and explored the drivers of change using multinomial logistic regression analysis and an information theoretical approach. We found distinct trends among oak forest types, reflecting the differences in oak economic value, protection status and management schemes: cork oak forests were the most persistent (62%), changing mostly to pines and eucalypt; holm oak forests were less persistent (53.2%), changing mostly to agriculture; and deciduous oak forests were the least persistent (45.7%), changing mostly to shrublands. Drivers of change had distinct importance across oak forest types, but drivers from anthropogenic origin (wildfires, population density, and land accessibility) were always among the most important. Climatic extremes were also important predictors of oak forest changes, namely extreme temperatures for evergreen oak forests and deficit of precipitation for deciduous oak forests. Our results indicate that under increasing human pressure and forecasted climate change, evergreen oak forests will continue declining and deciduous oak forests will be replaced by forests dominated by more xeric species. In the long run, multiple disturbances may change competitive dominance from oak forests to pyrophytic shrublands. A better understanding of forest dynamics and the inclusion of anthropogenic drivers on models of vegetation change will improve predicting the future of Mediterranean oak forests.
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Mudança Climática , Florestas , Quercus , Agricultura , PortugalRESUMO
This experiment evaluated forage production, sward structure, stocking rate, weight gain per area and nutritive value of forage as grazed by beef heifers on Alexandergrass (Urochloa plantaginea (Link) Hitch) pasture fertilized with nitrogen (N): 0; 100; 200 or 300 kg of N/ha. The experiment was a completely randomized design following a repeated measurement arrangement. The experimental animals were Angus heifers with initial age and weight of 15 months and 241.5±5 kg, respectively. The grazing method was continuous, with put-and-take stocking. N utilization, regardless of the level, increase by 25% the daily forage accumulation rate and the weight gain per area by 23%. The level of 97.2 kg N/ha leads to a higher leaf blade mass and increases by 20% the leaf:stem ratio. Alterations in sward structure changes the nutritive value of forage as grazed. The utilization of 112.7 kg of N/ha allows the highest stocking rate (2049.8 kg of BW/ha), equivalent to 7.5 heifers per hectare.
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Ração Animal/análise , Nitrogênio/farmacologia , Valor Nutritivo , Poaceae/crescimento & desenvolvimento , Criação de Animais Domésticos , Animais , Bovinos , Feminino , Poaceae/química , Poaceae/efeitos dos fármacos , Estações do Ano , Aumento de PesoRESUMO
Embedded extrusion 3D bioprinting is a rapidly emerging additive manufacturing methodology that provides a precise spatial deposition of synthetic or natural-origin low-viscosity bioinks during the extrusion printing process. Such a strategy has to date unlocked the freeform extrusion biofabrication of complex micro-to-macro-scale living architectures for numerous applications, including tissue engineering and in vitro disease modeling. In this chapter, we describe a suspension bioprinting methodology leveraging a continuous viscoelastic biopolymer supporting bath functionalized with divalent calcium cations to enable a rapid processing of user-defined bioinks toward architecturally complex 3D in vitro tumor models. This highly simple and cost-effective viscoelastic supporting bath enables a full freeform biofabrication of cell-laden 3D tumor-mimetic architectures that exhibit structural stability in culture post-printing. The cytocompatibility of the supporting bath, its ease of removal from biofabricated living constructs, and its adaptability for processing different ECM-mimetic bioinks open avenues for multi-scale fabrication of numerous types of physiomimetic 3D tumor models for preclinical screening of candidate therapeutics.
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Bioimpressão , Neoplasias , Humanos , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Biomimética , Neoplasias/terapia , Alicerces Teciduais/química , Hidrogéis/químicaRESUMO
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in adults, especially in patients over the age of 50. It manifests most commonly with an intense headache and visual symptoms. Although constitutional symptoms are also frequent in GCA, these can be dominant in 15% of patients at first presentation and 20% of patients when relapsing. Treatment with high-dose steroids should be initiated as soon as possible to rapidly control the inflammatory symptoms and prevent ischemic complications, the most feared being blindness from anterior ischemic optic neuropathy. We present a case of a 72-year-old man who presented to the emergency department with a right temporal headache with retroocular radiation associated with scalp hyperesthesia, without any visual symptoms. The patient also reported low-grade fever, night sweats, anorexia, and weight loss over the last two months. The physical exam revealed a tortuous and indurated right superficial temporal artery, which was tender to palpation. The ophthalmological examination was normal. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated, and he also had inflammatory anemia with a hemoglobin of 11.7 g/L. Due to this clinical presentation as well as the elevation of inflammatory markers, the diagnosis of temporal arteritis was suspected, and the patient was started on prednisolone (1 mg/kg). A right temporal artery biopsy was performed on the first week after the initiation of corticotherapy and was negative. After treatment initiation, there was a remission of symptoms accompanied by a decrease and normalization of inflammatory markers. However, after steroid tapering, there was a reappearance of constitutional symptoms but without any other organ-specific symptoms, such as headache, visual loss, arthralgia, or other. The corticosteroid dose was increased to the initial dosage, but there was no improvement in the symptoms this time. After the exclusion of other causes of the constitutional syndrome, a positron-emission tomography (PET) scan was performed, which showed a grade 2 aortitis. The diagnosis of giant cell aortitis was assumed, and given the lack of clinical response to corticotherapy, tocilizumab was initiated with a resolution of constitutional symptoms as well as a normalization of inflammatory markers. In conclusion, we report a case of temporal cell arteritis that further progressed to aortitis manifesting solely with constitutional symptoms. Furthermore, there was no optimal response to corticotherapy and no improvement with tocilizumab, therefore making this a case with a unique and infrequent clinical course. GCA is characterized by a wide variety of symptoms and organ involvement, and although it most frequently affects temporal arteries, it can be associated with aortic involvement that can cause life-threatening structural complications, highlighting the need for a high suspicion index for this condition.
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Bioengineering close-to-native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modeling toolboxes. Herein, pancreatic cancer living units-so termed cancer-on-a-bead models-are generated. Such user-programmable in vitro platforms exhibit biomimetic multicompartmentalization and tunable integration of cancer associated stromal elements. These stratified units can be rapidly assembled in-air, exhibit reproducible morphological features, tunable size, and recapitulate spatially resolved tumor-stroma extracellular matrix (ECM) niches. Compartmentalization of pancreatic cancer and stromal cells in well-defined ECM microenvironments stimulates the secretion of key biomolecular effectors including transforming growth factor ß and Interleukin 1-ß, closely emulating the signatures of human pancreatic tumors. Cancer-on-a-bead models also display increased drug resistance to chemotherapeutics when compared to their reductionistic counterparts, reinforcing the importance to differentially model ECM components inclusion and their spatial stratification as observed in vivo. Beyond providing a universal technology that enables spatial modularity in tumor-stroma elements bioengineering, a scalable, in-air fabrication of ECM-tunable 3D platforms that can be leveraged for recapitulating differential matrix composition occurring in other human neoplasias is provided here.
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Neoplasias Pancreáticas , Microambiente Tumoral , Bioengenharia , Linhagem Celular Tumoral , Matriz Extracelular/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias PancreáticasRESUMO
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by the polyoma John Cunningham (JC) virus. This virus is rarely pathogenic in immunocompetent individuals, being associated with profound cellular immunosuppression. We present a case of a 72-year-old woman with schizoaffective disorder who presented to the emergency department with dysarthria and right hemiataxia. The initial computer tomography was normal and the diagnosis of ischemic stroke was first assumed. However, during hospitalization there was a progressive worsening of symptoms with cerebellar ataxia, and the magnetic resonance revealed a lesion in the right middle cerebellar peduncle hypointense in T1 and hyperintense on T2/fluid attenuated inversion recovery (FLAIR) sequence, suggestive of PML. Although the first cerebrospinal fluid analysis was negative, the second one was positive for the JC virus. Furthermore, due to radiological and clinical progression, mirtazapine was started and the patient underwent a course of intravenous immunoglobulin, with no response. In parallel, causes of immunosuppression were investigated, which led to the diagnosis of idiopathic CD8+ lymphocytopenia. Due to rapid progression of symptoms and radiological worsening of lesions, pembrolizumab was administered. After the first administration of pembrolizumab there was a transitory clinical stabilization. However, shortly after the second administration of pembrolizumab, the patient developed stridor with bilateral vocal cord paralysis and subsequent symptom progression, which led to the death of the patient three months after the appearance of initial symptoms. In conclusion, we report a case of a PML in a patient with idiopathic CD8+ lymphocytopenia, enhancing the need for a high suspicion index for this entity as well as for occult and less frequent forms of immunosuppression. Although there have been various case reports of favourable outcomes with pembrolizumab for PML, more research is needed, particularly to identify patient factors that might be associated with better responses to this therapy.
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Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovative therapeutics. Diverse bioengineering approaches exploiting patient-derived organoids, cancer-on-a-chip platforms, and 3D bioprinted living constructs have been rapidly emerging in an endeavor to seamlessly recapitulate major tumor-stroma biodynamic interactions in a preclinical setting. Gathering on this, herein we showcase and discuss the most recent advances in bio-assembling pancreatic tumor-stroma models that mimic key disease hallmarks and its desmoplastic biosignature. A reverse engineering perspective of pancreatic tumor-stroma key elementary units is also provided and complemented by a detailed description of biodesign guidelines that are to be considered for improving 3D models physiomimetic features. This overview provides valuable examples and starting guidelines for researchers envisioning to engineer and characterize stroma-rich biomimetic tumor models. All in all, leveraging advanced bioengineering tools for capturing stromal heterogeneity and dynamics, opens new avenues toward generating more predictive and patient-personalized organotypic 3D in vitro platforms for screening transformative therapeutics targeting the tumor-stroma interplay.
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BACKGROUND AND OBJECTIVE: Nowadays the "low sample size, large dimension" scenario is often encountered in genetics and in the omic sciences, where the microarray data is typically formed by a large number of possibly dependent small samples. Standard methods to solve the k-sample problem in such a setting are of limited applicability due to lack of theoretical validation for large k, lengthy computational times, missing software solutions, or inability to deal with statistical dependence among the samples. This paper presents the R package Equalden.HD to overcome the referred limitations. METHODS: The package implements several tests for the null hypothesis that a large number of samples follow a common density. These methods are particularly well suited to the "low sample size, large dimension" setting. The implemented procedures allow for dependent samples. For each method Equalden.HD reports, among other things, the standardized value of the test statistic and the corresponding p-value. The package also includes two high-dimensional genetic data sets, Hedenfalk and Rat, which are used in this paper for illustration purposes. RESULTS: The usage of Equalden.HD has been illustrated through the analysis of Hedenfalk and Rat genetic data. Statistical dependence among the samples was found for both genetic data sets. The application of an appropriate k-sample test within Equalden.HD rejected the null hypothesis of inter-samples homogeneity. The methods were used to test for the within groups homogeneity in cluster analysis too, which is usually performed when the k samples are found to be significantly different. Equalden.HD helped to identify the individuals which are responsible for the lack of homogeneity of the samples. The limitations of the standard Kruskal-Wallis test for the identification of homogeneous clusters have been highlighted. CONCLUSIONS: The methods implemented by Equalden.HD are the unique omnibus nonparametric k-sample tests that have been validated as k grows. Furthermore, the package provides suitable corrections for possibly dependent samples, which is another distinctive feature. Thus, the package opens new doors for the statistical analysis of omic data. Limitations of standard methods (e.g. Anderson-Darling and Kruskal-Wallis) and existing software solutions in the setting with a large k have been emphasized.
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Software , Animais , Análise por Conglomerados , Ratos , Tamanho da AmostraRESUMO
INTRODUCTION: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. METHODS: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. RESULTS: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. CONCLUSIONS: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.
INTRODUÇÃO: A população de doentes com hemofilia (DCH) representa uma população com alta prevalência de infeção pelo virus da hepatite C (VHC), atendendo à utilização passada de derivados sanguíneos contaminados. Apesar de os objetivos terapêuticos nesta população serem semelhantes aos da população geral, estudos de vida real com follow-up de longa data são ainda escassos. O nosso objetivo consistiu em avaliar os outcomes infeção VHC, bem como, os resultados da terapéutica antivírica nos DCH. MÉTODOS: Foi avaliada retrospetivamente uma coorte unicêntrica de DCH com positividade para anti-VHC. Os outcomes registados foram a ocorrência de clearance espontêneo, resposta virológica sustentada (RVS), desenvolvimento de doença hepática terminal e mortalidade. RESULTADOS: De 131 DCH, 73 (55.7%) apresentavam positividade para o anticorpo VHC. Durante um follow-up médio de 22 anos, 46 doentes (63.9%) desenvolveram hepatite crónica C, 16 (34.8%) dos quais com desenvolvimento de cirrose. Trinta e quatro DCH foram tratados, a maioria (n = 32) exposta previamente a regimes baseados no interferão (IFN) com RVS de 40.6%. Antivíricos de ação direta foram utilizados em 14 doentes experimentados a IFN e 2 naïves com uma taxa de RVS geral de 100%. Morte foi observada em 17 doentes (23.3%), apenas 4 relacionadas à doença hepática. Destes nenhum tinha atingido RVS. CONCLUSÕES: Descrevemos os outcomes de uma coorte portuguesa de DCH e VHC após duas décadas de follow-up, mostrando uma mortalidade inferior à previamente descrita. As taxas de RVS mostradas foram comparáveis com as da população geral salientando a importancia do tratamento precoce.