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1.
J Viral Hepat ; 31(6): 309-319, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38483035

RESUMO

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.


Assuntos
Antivirais , Genótipo , Hepacivirus , Hepatite C Crônica , Humanos , Feminino , Antivirais/uso terapêutico , Estudos Retrospectivos , Adulto , Adolescente , Pessoa de Meia-Idade , Masculino , Adulto Jovem , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Resultado do Tratamento , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Fatores Sexuais
2.
Przegl Epidemiol ; 78(1): 16-21, 2024 Jun 07.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-38904308

RESUMO

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.


Assuntos
Actinomicose , Tonsilite , Humanos , Feminino , Adulto , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Tonsilite/microbiologia , Tonsilite/tratamento farmacológico , Tonsilite/diagnóstico , Antibacterianos/uso terapêutico , Actinomicose Cervicofacial/diagnóstico , Actinomicose Cervicofacial/tratamento farmacológico , Abdome
3.
J Med Virol ; 95(6): e28864, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37310140

RESUMO

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.


Assuntos
Antígenos de Grupos Sanguíneos , COVID-19 , Adulto , Humanos , Autoanticorpos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Estudos Soroepidemiológicos
4.
J Med Virol ; 95(7): e28962, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37466326

RESUMO

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.


Assuntos
Poluição do Ar , COVID-19 , Adulto , Humanos , SARS-CoV-2 , Exposição Ambiental , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Progressão da Doença
5.
Transfusion ; 63(2): 349-359, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36537152

RESUMO

BACKGROUND: In Poland, hepatitis A virus (HAV) RNA screening was performed in plasma for fractionation usually immediately before shipment. OBJECTIVE: Our goal was to study epidemiology, rate of transfusion transmitted HAV during epidemic (2017-2019), and viral characteristics of infected plasma donors. STUDY DESIGN AND METHODS: HAV RNA was tested in 1,866,590 donations from 1,210,423 donors using RT-PCR in mini pools of 96 (MP96) or TMA in MP16. Virological characteristics included RNA level (RL), antibody testing, and sequencing. RESULTS: Twenty-one HAV infections were identified (1.13/100,000 donations; 95% confidence interval [95% CI]: 0.74-1.72) and (1.73/100,000 donors; 95% CI: 1.35-2.65). The Blood Transfusion Centers were also informed about three donors, who were hospitalized for hepatitis A soon after their blood donation. In addition, we identified a donor, who had reactive result for HAV after receiving HAV vaccination. He tested positive twice 10 days after receiving the first and the second dose. The highest RL was 16 million IU/ml, mean 1,706,905 IU/ml, and median 220 IU/ml. The longest detectable RL lasted for 113 days. HAV-infected donors were seronegative (36%) or IgM positive (64%). We followed up on 12 HAV contaminated blood components issued for transfusion. In two out of seven identified patients viral transmission was confirmed (28.6%). CONCLUSION: Based on our results, we propose a 6 month deferral after HAV infection and 14 days post HAV vaccination. The infectivity rate was below 30%. The HAV RNA testing could be considered as an additional safeguard against HAV transmission at the time of increased incidence of HAV infections in the general population.


Assuntos
Vírus da Hepatite A , Hepatite A , Masculino , Humanos , Doadores de Sangue , Polônia/epidemiologia , RNA Viral , Transfusão de Componentes Sanguíneos , Hepatite A/epidemiologia , Vírus da Hepatite A/genética
6.
Pol Merkur Lekarski ; 51(3): 189-193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589101

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados , Hepatite B , Esclerose Múltipla , Ativação Viral , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Nucleosídeos , Esclerose Múltipla/complicações , Anticorpos Anti-Hepatite B , Hepatite B/complicações
7.
BMC Neurol ; 22(1): 91, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287619

RESUMO

BACKGROUND: COVID-19, caused by a novel coronavirus SARS-CoV 2 has rapidly developed into pandemic. This infectious disease affecting mainly respiratory system may cause multiple systemic disorders. With increasing number of new infected patients there are more and more cases with neurological complications secondary to COVID-19. CASE PRESENTATION: Here we present a case of 67-years old Polish male with previously no comorbidities, who has developed bilateral paralysis of peroneal nerve after SARS-CoV 2 infection. Prior to the hospitalization he presented cough and fever and weakness. RT-PCR was reported positive for COVID-19 infection. Then he developed pneumonia and respiratory failure with bilateral lung consolidations on radiological examination. Laboratory findings revealed elevated levels of D-dimer, CRP, AspAT, GGTP, PCT and serum glucose. After discharge from hospital he was diagnosed with thrombophlebitis and prediabetes on follow-up visits. Due to problems with walking, numbness of toes and involuntary muscle spasms in hands, the patient went to the Neurological Outpatient Clinic. After neurological examination bilateral paralysis of peroneal nerve was revealed. CONCLUSIONS: In this report we want to highlight one of the unexpected presentations of SARS-CoV 2 infection and emphasize the importance of neurological examination in COVID-19 patients.


Assuntos
COVID-19 , Pneumonia , Idoso , COVID-19/complicações , Humanos , Masculino , Paralisia , Nervo Fibular , Caminhada
8.
Neurol Neurochir Pol ; 56(3): 220-227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35735245

RESUMO

Changes in the immune system associated with ageing are known as immunosenescence. This is characterised by a decline in immune response, chronic inflammation and an increased risk of autoimmune diseases. A chronic inflammatory process with persistent production of proinflammatory mediators increases the risk for morbidity and mortality related to age, and has been dubbed 'inflamm-ageing'. Immunosenescence is associated with a decrease in the number of naive T and B cells, NK cells and disruption of the pro- and anti-inflammatory balance by changes in the production of cytokines. In fact, ageing of the immune system has a complex network of underlying causes which include not only natural mechanisms of senescence but also chronic disorders, lifestyle, environmental and epigenetic factors, and infections. Moreover, immunosenescence has an influence on the course of chronic diseases which have an onset in young adults, such as multiple sclerosis (MS). Current disease modifying therapies (DMTs) in MS aim to reduce the frequency of relapses and to slow disease progression, but they do not necessarily stop the accumulation of disability related to disease progression. Some features of immunosenescence found in aged healthy controls are already observed in MS patients at a younger age. The older population is characterised by an increased susceptibility to infections, a poor response to vaccinations, and a higher risk of developing cancer, vascular diseases and neurodegeneration. Immunosenescence is an important factor influencing the course of MS, and the safety and effectiveness of DMTs. The relationship between the pathogenic process underlying the development of MS and immunosenescence requires further investigation.


Assuntos
Imunossenescência , Esclerose Múltipla , Idoso , Envelhecimento , Progressão da Doença , Humanos , Imunossenescência/fisiologia , Inflamação
9.
Liver Int ; 41(8): 1789-1801, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33655628

RESUMO

BACKGROUND AND AIMS: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.


Assuntos
Antivirais , Hepatite C Crônica , Antivirais/efeitos adversos , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Estudos Retrospectivos , Resposta Viral Sustentada
10.
J Gastroenterol Hepatol ; 36(7): 1944-1952, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33171526

RESUMO

BACKGROUND AND AIMS: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). METHODS: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. RESULTS: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse. CONCLUSIONS: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.


Assuntos
Infecções por HIV , Hepatite C , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Benzimidazóis , Ciclopropanos , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Cirrose Hepática/tratamento farmacológico , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , Estudos Retrospectivos , Sulfonamidas
11.
J Gastroenterol Hepatol ; 35(7): 1238-1246, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31734959

RESUMO

BACKGROUND AND AIM: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. METHODS: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. RESULTS: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. CONCLUSIONS: GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.


Assuntos
Benzofuranos/administração & dosagem , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas , Antivirais/administração & dosagem , Carbamatos , Comorbidade , Ciclopropanos , Análise de Dados , Quimioterapia Combinada , Feminino , Infecções por HIV/epidemiologia , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Sulfonamidas , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
12.
Przegl Epidemiol ; 74(4): 644-651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33861031

RESUMO

Actinomycosis is one of the greatest 'chameleons' among infectious diseases. It may imitate inflammation, abscess or a neoplasmatic tumor. Moreover, correct diagnosis is even more challenging due to the fact that the disease takes on various forms like: cervicocephalic, abdominal, or affects the reproductive organs. In order to highlight the diagnostic difficulties of actinomycosis, we have decided to describe six cases of female patients (aged 31-73 years, mean age: 52 years) hospitalized due to actinomycosis in the Department of Infectious Diseases and Hepatology between 2014-2019. Additionally, a case of one patient was described in detail as the course of her disease was exceptionally non-specific. Only in 2 of 6 patients the primary diagnosis was correct. The four other patients were initially suspected with cancer or inflammation. Three of the patients were diagnosed with the abdominal form of actinomycosis, one - neck and head, and one presented both locations. Only histopathological examinations during invasive procedures allowed to state the final diagnosis. An adequate diagnosis was associated with a number of additional tests and delayed appropriate treatment. WBC and CRP were within normal range in all patients. Four patients completed treatment successfully after 60-192 days, one is still on therapy and one is lost to follow-up. In conclusion, common features of actinomycosis presented in this case series include predominance of female gender, abdominal localization and lack of typical symptoms. What is more, therapy with antibiotics, mainly doxycycline and beta-lactams resulted in complete regression of lesions in the majority of cases. Given the examples of our patients we believe that actinomycosis should be considered in the differential diagnosis of all abdominal tumors, especially in women. Abbreviations: WBC - white blood cells, CRP - C-reactive protein, CT - computed tomography, IUD - Intra-Uterine Device, i.v. - intravenous.


Assuntos
Actinomicose , Dispositivos Intrauterinos , Abscesso/tratamento farmacológico , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Antibacterianos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Polônia
13.
Przegl Epidemiol ; 74(1): 3-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32500978

RESUMO

BACKGROUND: [i]Clostridium difficile[/i] infections become a serious problem in terms of nosocomial infections, as well as a consequence of common use of antibiotics. AIM: The aim of the study was to evaluate [i]Clostridium difficile[/i] carriage in patients admitted to the Clinical Department of Infectious Diseases and Hepatology without acute or chronic diarrhea and to assess the impact of antibiotic treatment on the development of enteritis in hospital. Other factors that may affect the risk of infection were also analyzed. RESULTS: Fourteen patients (14%) were carriers of [i]Clostridium difficile[/i] at admission. Second assessment taken after fourteen days of antibiotic treatment showed decrease in GDH antigen prevalence to eight subjects (12.1%). Three patients (3%) had diarrhea during hospitalization, and the toxins A and/or B were found in them. CONCLUSIONS: The frequency of [i]Clostridium difficile[/i] carriage among adults in Poland may be underestimated. Screening for Clostridium difficile GDH antigen may be useful although do not provide definite prognosis of symptomatic disease during ceftriaxone treatment. The risk of Clostridium difficile infection may be reduced mainly by rationalizing antibiotic therapy and following appropriate procedures.


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile , Infecções por Clostridium/epidemiologia , Adulto , Infecções por Clostridium/tratamento farmacológico , Feminino , Hospitais , Humanos , Masculino , Polônia/epidemiologia , Prevalência , Fatores de Risco
14.
Clin Infect Dis ; 69(11): 1969-1979, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30715261

RESUMO

BACKGROUND: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. METHODS: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. RESULTS: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. CONCLUSIONS: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. CLINICAL TRIALS REGISTATION: NCT01401400.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/metabolismo , Interferons/metabolismo , Adulto , Antivirais/uso terapêutico , Feminino , Técnicas de Genotipagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos
16.
BMC Infect Dis ; 18(1): 580, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445916

RESUMO

BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.


Assuntos
Anilidas/administração & dosagem , Benzimidazóis/uso terapêutico , Carbamatos/administração & dosagem , Farmacorresistência Viral Múltipla/efeitos dos fármacos , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Compostos Macrocíclicos/administração & dosagem , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Uracila/análogos & derivados , Uridina Monofosfato/análogos & derivados , 2-Naftilamina , Adulto , Idoso , Anilidas/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Estudos de Coortes , Ciclopropanos , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Humanos , Interferons/administração & dosagem , Interferons/efeitos adversos , Lactamas Macrocíclicas , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prolina/análogos & derivados , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Ritonavir/efeitos adversos , Sofosbuvir , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos , Uridina Monofosfato/uso terapêutico , Valina , Adulto Jovem
18.
Mediators Inflamm ; 2017: 3480234, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28827897

RESUMO

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(-) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.


Assuntos
Hepatite B Crônica/sangue , Queratina-18/sangue , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Humanos , Inflamação/sangue , Fígado/metabolismo , Masculino , Fragmentos de Peptídeos/sangue , Adulto Jovem
19.
Przegl Epidemiol ; 70(1): 11-4, 103-6, 2016.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-27344467

RESUMO

Of 20 million of patients infected with hepatitis E virus (HEV) worldwide 57 thousand dies each year. HEV-infection is not longer regarded as a diseases in developing endemic countries of Asia, Africa and Latin America. The majority of European countries faces increasing number of endemic infections. They are caused by seven different genotypes and be responsible for acute and chronic infections. HEV is of zoonotic origin causing infections in pigs and boars which are a source of infection for humans. Infections occur orally after consumption of infected water or meat. HEV-infection is most dangerous for patients receiving immunosuppressive therapy, infected with HIV, after transplantations of solid organs and elderly. In some patients, including pregnant women, acute HEV has a serious course with fatalities reaching even 25%. Chronic HEV-infection may develop in patients following solid organ transplantations and requires long-term antiviral therapy. HEV-infection is a growing public health problem in Europe, which implies the necessity of routine screening in selected populations, especially immunocompromised.


Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/transmissão , Hepatite E/virologia , Zoonoses/transmissão , Zoonoses/virologia , Doença Aguda , Animais , Doença Crônica , Doenças Transmissíveis Emergentes/epidemiologia , Reservatórios de Doenças , Europa (Continente) , Humanos , Suínos , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia
20.
Pol Merkur Lekarski ; 40(236): 117-21, 2016 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-27000818

RESUMO

Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods.


Assuntos
Encefalopatia Hepática/diagnóstico , Diagnóstico Precoce , Encefalopatia Hepática/epidemiologia , Humanos , Cirrose Hepática
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