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1.
Postepy Dermatol Alergol ; 39(6): 1128-1133, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36686024

RESUMO

Introduction: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is associated with the risk of anogenital and oropharyngeal cancers. Men who have sex with men (MSM) are at a high risk of HPV infection. However, little up-to-date data are available regarding the prevalence of HIV and HPV co-infection in MSM in Poland. Aim: To evaluate the prevalence, genotype distribution and risk factors for HPV infection among HIV-positive MSM living in Lower Silesia. Material and methods: A total of 54 HIV-positive and 28 HIV-negative MSM participated in the study. The polymerase chain reaction was performed to detect HPV from oral and anal swabs. A self-applied written questionnaire was conducted to collect sociodemographic and behavioural data. Results: The prevalence rates of oral and anal HPV infection were higher in HIV-infected MSM than in HIV-negative MSM. Statistical analysis showed that the prevalence of high oncogenic genotypes, HPV 16 and HPV 18, at the anal site was significantly higher in patients with lower CD4 cell counts, in addition, HPV 18 infection was significantly more frequent in patients with higher levels of HIV RNA. Moreover, HPV 33 and HPV 52 at the anal site were significantly more common in patients with lower nadir CD4. Conclusions: This is the first report of HPV infection among Polish HIV-infected MSM. Our results show that HIV-related immunodeficiency is associated with a higher prevalence of high-risk HPV infections, therefore early detection of HIV infection and initiation of antiretroviral therapy might reduce the risk of HPV-related diseases.

2.
J Psychiatry Neurosci ; 46(1): E166-E175, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33464780

RESUMO

Background: Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods: The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery-Åsberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results: Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (ß = -0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery-Åsberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.


Assuntos
Antivirais/farmacologia , Depressão , Transtorno Depressivo Maior , Hepatite C Crônica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Interferon-alfa/farmacologia , Polietilenoglicóis/farmacologia , Ribavirina/farmacocinética , ortoaminobenzoatos/metabolismo , Adulto , Antivirais/efeitos adversos , Estudos Transversais , Depressão/imunologia , Depressão/metabolismo , Depressão/fisiopatologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Indolamina-Pirrol 2,3,-Dioxigenase/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Interferon-alfa/efeitos adversos , Ácido Cinurênico/metabolismo , Cinurenina/efeitos dos fármacos , Cinurenina/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Ribavirina/efeitos adversos , Triptofano/efeitos dos fármacos , Triptofano/metabolismo , ortoaminobenzoatos/sangue
3.
Przegl Epidemiol ; 74(1): 33-42, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32500982

RESUMO

BACKGROUND: Immunosuppressed patients, also those who are HIV-positive patients, are susceptible to oral cavity fungal infections. AIM OF STUDY: In this study, we aimed to show differences in qualitative composition of oral cavity flora between HIV-positive people and healthy controls and identify factors which affect fungal oral cavity flora. MATERIALS AND METHODS: The study group contained HIV-positive people and a control group of healthy people. All cultured species were analysed using MALDI-TOF MS. RESULTS: More HIV-positive people had two or more fungus species present than controls (p=0.008). Seven species were cultured in the study group compared to three in the control group. Smoking was associated with higher prevalence of C. albicans (p=0.03), C. glabrata (p=0.026), C. tropicalis (p=0.01). Dental prosthesis or braces was also associated with presence of more species (p=0.04).The lower level of lymphocytes CD4+ was not associated with fungus presence in oral cavity. CONCLUSIONS: HIV infection is associated with changes to oral cavity fungal flora. Given the higher number of non-albicans species among HIV-positive patients it is important to individually choose a treatment for such patients' fungal infections. Proper oral hygene and not smoking can reduce prevalence of fungi in oral cavity. Patients' immunological status did not have an impact on the frequency of Candida species isolation from the oral cavity.


Assuntos
Candidíase/epidemiologia , Infecções por HIV/epidemiologia , Boca/microbiologia , Adulto , Candida albicans , Feminino , Infecções por HIV/microbiologia , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Polônia/epidemiologia
4.
J Viral Hepat ; 26(6): 635-643, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30702208

RESUMO

The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.


Assuntos
Antivirais/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Hepatite C Crônica/diagnóstico por imagem , Substância Branca/efeitos dos fármacos , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Imagem de Tensor de Difusão , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Substância Branca/diagnóstico por imagem
5.
Euro Surveill ; 23(21)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29845931

RESUMO

BACKGROUND: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. AIM: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends. METHODS: In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression. RESULTS: Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe. CONCLUSIONS: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Disparidades em Assistência à Saúde/estatística & dados numéricos , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Falha de Tratamento
6.
Przegl Epidemiol ; 72(3): 363-370, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30394060

RESUMO

INTRODUCTION: Malaria is caused by the Plasmodium spp. which are spread through Anopheles mosquitoes. Disease is not endemic in Poland currently but can be brought from other countries, mostly from Africa and Asia. The main sign of the disease is fever with shivers repeated periodically. There is highly effective chemoprophylaxis available and treatment, which should be given quickly CASE REPORT: A 35-year-old man have worked monthly in Nigeria since two years. He was using Malarone chemoprophylaxis, but contrary to recommendations. Patient presented to a hospital after four days of having fever in a medium-serious state. He reported three similar incidents in the past. Physical examination revealed hepatomegaly, depressive state, oliguria and diarrhoea. Lab tests showed DIC with thrombocytopenia, renal injury, liver injury, hypoalbuminemia. ECG indicated myocardial ischemia. Malaria Rapid Test and blood smear confirmed Plasmodium falciparum infection with 9,9% parasitemia. When antimalarial treatment was given, patient condition improved, but after three days in hospital he got pneumonia as a complication of malaria ­ antibiotic admission was committed. Moreover, quinine caused temporary deafness and serological tests revealed chronic HBV infection. After 23-days of hospitalisation the patient was discharged in a good condition. A month later patient went to follow-up and only mild anaemia was shown. CONCLUSIONS: This case shown that even such severe disease like malaria can be cured well without serious complications if patient will be diagnosed quickly. Moreover patient's experience and respecting symptoms improve prognosis. There also should be stronger emphasis on the role of chemoprophylaxis ­ patient did not use it properly, so it did not have to prevent development of malaria.


Assuntos
Antimaláricos/uso terapêutico , Doenças Transmissíveis Importadas/diagnóstico , Malária Falciparum/diagnóstico , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Ácido Clavulânico/uso terapêutico , Doenças Transmissíveis Importadas/complicações , Doenças Transmissíveis Importadas/tratamento farmacológico , Humanos , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Masculino , Nigéria , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Polônia
7.
BMC Infect Dis ; 15: 556, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26637466

RESUMO

BACKGROUD: Cytokine response against hepatitis C virus (HCV) is likely to determine the natural course of infection as well as the outcome of antiviral treatment. However, the role of particular cytokines remains unclear. The current study analyzed activation of cytokine response in chronic hepatitis C patients undergoing standard antiviral treatment. METHODS: Twenty-two patients were treated with pegylated interferon and ribavirin. Twenty-six different cytokine transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy and correlated with therapy outcome as well as with clinical and liver histological data. RESULTS: We found that patients who achieved sustained virological response (SVR) showed higher pretreatment cytokine response when compared to subjects in whom therapy was unsuccessful. The differentially expressed factors included IL-8, IL-16, TNF-α, GM-CSF, MCP-2, TGF-ß, and IP-10. Serum ALT activity and/or histological grading also positively correlated with the expression of IL-1α, IL-4, IL-6, IL-10, IL-12, IL-15, GM-CSF, M-CSF, MCP-2 and TGF-ß. CONCLUSION: Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity.


Assuntos
Antivirais/administração & dosagem , Citocinas/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interferon-alfa/administração & dosagem , Leucócitos Mononucleares/metabolismo , Ribavirina/administração & dosagem , Adulto , Idoso , Citocinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Hepacivirus/imunologia , Hepatite C Crônica/metabolismo , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Postepy Hig Med Dosw (Online) ; 67: 186-91, 2013 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-23619217

RESUMO

INTRODUCTION: Hepatitis C virus (HCV) is a primarily hepatotropic virus, but hepatocytes are not the only localization of its replication. It is still unclear if extrahepatic HCV replication, measured as the detection of HCV RNA negative strand in peripheral blood mononuclear cells (PBMCs) before initiation of treatment, has an influence on therapy response. Detection of HCV RNA in extrahepatic sites for assessment of therapy efficacy is not routinely used in clinical practice. The aim of the study was to evaluate whether the replication of HCV in PBMCs affects the rate of sustained virological response (SVR). MATERIALS AND METHODS: The study group comprised 55 patients with chronic hepatitis C, originally treatment naive. They were treated with pegylated interferon (PEG-IFN) alpha 2a and ribavirin, with the standard dosing schedule. Parallel serum samples for HCV RNA and PBMC samples for HCV RNA negative strand were obtained at baseline, at the end of treatment and 24 weeks after finishing therapy. RESULTS: Undetectable HCV RNA in serum at the end of therapy was found in 48 patients (87.3%), while 33 patients (60.0%) achieved sustained virological response (SVR) (51% for HCV genotype 1 and 78% for genotype 3, respectively). Fifteen individuals (31.3%) were relapsers. Factors associated with significantly higher rate of SVR were young age, mild or no fibrosis and infection with HCV genotype 3. HCV RNA negative strand in PBMCs before treatment was found in 21.8% (12 out of 55 patients). HCV RNA negative strand was detected at baseline more frequently in patients who later achieved SVR. Relapse appeared significantly more often in patients with negative strand at the end of therapy: in 2 out of 15 individuals compared to 0 out of 33 patients (p=0.03). CONCLUSIONS: Presence of negative HCV RNA strand in PBMCs before treatment may be suggested as a potential marker of good treatment response. Detection of negative strand at the end of therapy is a predictor of relapse.


Assuntos
Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares/virologia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Recidiva , Ribavirina/uso terapêutico , Adulto Jovem
9.
Viruses ; 15(12)2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38140673

RESUMO

In the last three decades, there has been a considerable improvement in human immunodeficiency virus (HIV) therapy. Acquired immunodeficiency syndrome (AIDS) is no longer a common cause of death for people living with HIV (PLWH) in developed countries, and co-infections with hepatitis viruses can be effectively managed. However, metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) are emerging threats these days, especially as the HIV-positive population gets older. The factors for MASLD development in PLWH are numerous, including non-specific (common for both HIV-positive and negative) and virus-specific. We focus on what is known for both, and in particular, on the burden of antiretroviral therapy (ART) for metabolic health and liver damage. We review data on contemporary drugs, including different groups and some particular agents in those groups. Among current ART regimens, the switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) and particularly its combination with integrase inhibitors (INSTIs) appear to have the most significant impact on metabolic disturbances by increasing insulin resistance, which over the years promotes the evolution of the cascade leading to metabolic syndrome (MetS), MASLD, and eventually metabolic dysfunction-associated steatohepatitis (MASH).


Assuntos
Fármacos Anti-HIV , Fígado Gorduroso , Infecções por HIV , Soropositividade para HIV , HIV-1 , Síndrome Metabólica , Humanos , Adenina/farmacologia , Antirretrovirais/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
10.
Cells ; 12(6)2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36980311

RESUMO

BACKGROUND: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. MATERIALS AND METHODS: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times-at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. RESULTS: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, LG/LG, and S/LG) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. CONCLUSIONS: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression.


Assuntos
Depressão , Hepatite C Crônica , Interferon alfa-2 , Triptofano , Adulto , Humanos , Antivirais/uso terapêutico , Depressão/genética , Depressão/metabolismo , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interferon alfa-2/efeitos adversos , Interferon alfa-2/farmacologia , Interferon alfa-2/uso terapêutico , Cinurenina , Polietilenoglicóis/farmacologia , Polimorfismo Genético , Estudos Prospectivos , Receptor 5-HT1A de Serotonina/genética , Ribavirina/efeitos adversos , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Triptofano/efeitos dos fármacos , Triptofano/metabolismo , Triptofano Hidroxilase/genética , Triptofano Oxigenase/genética
12.
Neuro Endocrinol Lett ; 32(1): 1-3, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21407153

RESUMO

BACKGROUND: Serious infections are rare complications of standard treatment in chronic hepatitis C with pegylated interferon alpha (Peg IFN) and ribavirin. CASE: We report two cases of life-threatening tubo-ovarian abscess (TOA) in women older than 40 year of age. No casual risk factors of TOA could be identified in them. In one case septic shock and acute renal failure occured. TOA was caused by endogenic bacteria (Porphyromonas asaccharolytica in the first case and Streptococcus intermedius in the latter). Surgical treatment and interruption of IFN therapy was necessary in both cases. CONCLUSIONS: Serious gynecological infections may have the significant negative influence on chronic hepatitis C therapy outcome. Because of the risk of TOA developing during IFN therapy gynecological care is needed in chronic hepatitis C management.


Assuntos
Abscesso Abdominal/microbiologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Ooforite/microbiologia , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Salpingite/microbiologia , Abscesso Abdominal/epidemiologia , Abscesso Abdominal/cirurgia , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Pessoa de Meia-Idade , Ooforite/epidemiologia , Ooforite/cirurgia , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Ribavirina/administração & dosagem , Fatores de Risco , Salpingite/epidemiologia , Salpingite/cirurgia
13.
Nat Med ; 27(10): 1836-1848, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34635855

RESUMO

Alterations in lipid metabolism might contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, no pharmacological agents are currently approved in the United States or the European Union for the treatment of NAFLD. Two parallel phase 2a studies investigated the effects of liver-directed ACC1/2 inhibition in adults with NAFLD. The first study ( NCT03248882 ) examined the effects of monotherapy with a novel ACC1/2 inhibitor, PF-05221304 (2, 10, 25 and 50 mg once daily (QD)), versus placebo at 16 weeks of treatment; the second study ( NCT03776175 ) investigated the effects of PF-05221304 (15 mg twice daily (BID)) co-administered with a DGAT2 inhibitor, PF-06865571 (300 mg BID), versus placebo after 6 weeks of treatment. The primary endpoint in both studies was percent change from baseline in liver fat assessed by magnetic resonance imaging-proton density fat fraction. Dose-dependent reductions in liver fat reached 50-65% with PF-05221304 monotherapy doses ≥10 mg QD; least squares mean (LSM) 80% confidence interval (CI) was -7.2 (-13.9, 0.0), -17.1 (-22.7, -11.1), -49.9 (-53.3, -46.2), -55.9 (-59.0, -52.4) and -64.8 (-67.5, -62.0) with 16 weeks placebo and PF-05221304 2, 10, 25 and 50 mg QD, respectively. The overall incidence of adverse events (AEs) did not increase with increasing PF-05221304 dose, except for a dose-dependent elevation in serum triglycerides (a known consequence of hepatic acetyl-coenzyme A carboxylase (ACC) inhibition) in 23/305 (8%) patients, leading to withdrawal in 13/305 (4%), and a dose-dependent elevation in other serum lipids. Co-administration of PF-05221304 and PF-06865571 lowered liver fat compared to placebo (placebo-adjusted LSM (90% CI) -44.6% (-54.8, -32.2)). Placebo-adjusted LSM (90% CI) reduction in liver fat was -44.5% (-55.0, -31.7) and -35.4% (-47.4, -20.7) after 6 weeks with PF-05221304 or PF-06865571 alone. AEs were reported for 10/28 (36%) patients after co-administered PF-05221304 and PF-06865571, with no discontinuations due to AEs, and the ACC inhibitor-mediated effect on serum triglycerides was mitigated, suggesting that PF-05221304 and PF-06865571 co-administration has the potential to address some of the limitations of ACC inhibition alone.


Assuntos
Acetil-CoA Carboxilase/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Inibidores Enzimáticos/administração & dosagem , Fígado/enzimologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Acetil-CoA Carboxilase/genética , Diacilglicerol O-Aciltransferase/genética , Método Duplo-Cego , Sinergismo Farmacológico , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Placebos
14.
Przegl Epidemiol ; 64(4): 465-71, 2010.
Artigo em Polonês | MEDLINE | ID: mdl-21473059

RESUMO

The paper presents the pathogenetic base of liver fibrosis in HIV/HCV co-infection. The factors influencing on fibrosis progression, dependent on progressive immunosuppression and the effects of antiretroviral drugs are discussed in details. Current diagnostic possibilities, including the role of histopathologic evaluation of liver tissue and non-invasive methods--serum fibrosis markers and elastometry--are presented.


Assuntos
Infecções por HIV/patologia , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Antivirais/uso terapêutico , Progressão da Doença , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico
15.
Adv Clin Exp Med ; 28(9): 1217-1222, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30811903

RESUMO

BACKGROUND: Depressive symptoms are frequent side effects of interferon α therapy (IFN-α). Both biological and psychological processes may occur concomitantly during hepatitis C treatment. OBJECTIVES: This study was carried out to determine the impact of biological (immune response) and psychological factors on formation of depressive symptoms and major depressive disorder (MDD) during hepatitis C treatment. MATERIAL AND METHODS: A total of 99 patients receiving pegylated IFN-α and ribavirin for chronic C type hepatitis participated in the prospective cohort study. Symptoms of depression were assessed with the MontgomeryÅsberg Depression Rating Scale (MADRS) during treatment and 24 weeks after treatment. Neuroticism was measured with the Eysenck Personality Questionnaire - Revised (EPQ-R/N). Diagnosis of MDD was made using the Present State Examination (PSE-10) and DSM-IV-TR criteria. Factor analysis was used to detect factors adding up to total severity of depressive symptoms. Predictors of MDD were investigated using logistic regression analysis. RESULTS: Factor analysis returned 3 factors: 1st - MADRS scores at weeks 0-12, 2nd - MADRS and N scores before treatment, 3rd - MADRS at the 24th week of treatment and 24 weeks after treatment. The total severity of depressive symptoms consisted of 3 components: personality-related before treatment, IFN-α-related during treatment and dependent on the effect of treatment. Regression analysis showed that a history of psychiatric disorders (OR = 4.8) and MADRS scores before treatment (OR = 1.25) were predictors of MDD, as opposed to level of neuroticism. CONCLUSIONS: The severity of depressive symptoms and MDD during the hepatitis C treatment was related to general depressive vulnerability, not to psychological factors related to neuroticism.


Assuntos
Antivirais/efeitos adversos , Depressão , Hepatite C Crônica , Interferon-alfa/efeitos adversos , Antivirais/uso terapêutico , Depressão/induzido quimicamente , Depressão/epidemiologia , Depressão/psicologia , Transtorno Depressivo Maior/epidemiologia , Quimioterapia Combinada , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/psicologia , Humanos , Interferon-alfa/uso terapêutico , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Ribavirina/efeitos adversos
16.
J Neurol Sci ; 399: 36-43, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30769221

RESUMO

The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24 weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.


Assuntos
Antivirais/farmacologia , Atenção/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Hepatite C/diagnóstico por imagem , Memória de Curto Prazo/efeitos dos fármacos , Adulto , Idoso , Anilidas/farmacologia , Anilidas/uso terapêutico , Antivirais/uso terapêutico , Encéfalo/diagnóstico por imagem , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/psicologia , Humanos , Lactamas Macrocíclicas , Compostos Macrocíclicos/farmacologia , Compostos Macrocíclicos/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão/efeitos dos fármacos , Projetos Piloto , Prolina/análogos & derivados , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Sulfonamidas , Valina
17.
Int J Infect Dis ; 80: 122-128, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30641198

RESUMO

INTRODUCTION: The aim of this study was to investigate brain bioelectrical activity disturbances in HCV-positive patients before and 24 weeks after interferon-free therapy (DAA), using visual (VEP) and brainstem (BAEP) evoked potentials and advanced magnetic resonance techniques. MATERIALS AND METHODS: 11 HCV-infected patients (6 women, 5 men, mean age 51 years old) and 30 healthy controls, sex and age-matched, were studied. Clinical neurological examinations, VEP, BAEP, diffusion tensor imaging (DTI) and perfusion weighted imaging (PWI) were performed. RESULTS: 11 patients achieved a sustained viral response, and liver fibrosis regression in APRI and in elastography were observed. The mean P100 latency was significantly shorter in HCV-patients after therapy compared to the values before treatment (p<0.05). The mean wave BAEP V latency and I-V interpeak latency were significantly longer in the HCV-infected patients before therapy compared to HCV-patients after therapy. CONCLUSIONS: This study confirms that treatment with DAA in patients with chronic HCV infection positively affects the bioelectrical activity of the brain. An increase in the amplitude of EP after treatment indicates an improvement in the activity of the cerebral cortex. EP examination may be a useful method of assessing the function of the nervous system before and after antiviral treatment.


Assuntos
Antivirais/uso terapêutico , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Encéfalo/virologia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , RNA Viral/isolamento & purificação
19.
Przegl Epidemiol ; 62(2): 383-91, 2008.
Artigo em Polonês | MEDLINE | ID: mdl-18807485

RESUMO

Liver diseases, mainly chronic viral hepatitis, recently have become the main cause of hospitalization and death in individuals with HIV infection. As HCV infection is predominant condition in this group of patients, treatment of hepatitis C is extremely important in halting hepatic injury. Large clinical trials (APRICOT, RIBAVIC, ACTG 5071) showed satisfactory efficacy and safety of therapy with pegylated interferon alpha and ribavirin. Other trials, searching ways to improve efficacy of chronic hepatitis C treatment in HIV co-infected individuals, are still running. Management possibilities include higher doses of ribavirin and, prolonged course of treatment. The article summarizes current state of knowledge in the field of chronic hepatitis C treatment in HIV/HCV-coinfected individuals.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Atenção Primária à Saúde/organização & administração , Ribavirina/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Comorbidade , Medicina Baseada em Evidências , Hepatite C Crônica/epidemiologia , Humanos , Polônia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
20.
Wiad Lek ; 61(1-3): 13-8, 2008.
Artigo em Polonês | MEDLINE | ID: mdl-18717037

RESUMO

UNLABELLED: Many articles concerning the hepatitis C virus (HCV) infection emphasize the role of cytokines Th1- and Th2-dependent. The aim of our study was to assess the changes in the concentration of cytokines (IL-2, IFN-gamma, IL-4, IL-10) determined by ELISA test in serum of HCV infected patients treated with interferon alpha (IFN-alpha) and ribavirine. RESULTS: The cytokine levels in HCV patients (n = 40) were similar to levels observed in healthy volunteers (p > 0.05). During IFN-alpha and ribavirine therapy no statistically significant changes in cytokine levels were observed in patients who achieved sustained virological response (SVR) compared to unsuccessfully treated patients (p > 0.05). CONCLUSIONS: 1. Serum is not useful compartment to determinate level of cytokines by ELISA method in chronic hepatitis C. 2. The measurement of cytokine levels using ELISA test was not confirmed to be useful in monitoring and assessment of the therapy results in HCV infected patients.


Assuntos
Citocinas/metabolismo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Masculino , Monitorização Fisiológica/métodos
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