RESUMO
BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.
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Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Fígado/metabolismo , Pele/patologia , Algoritmos , Alopurinol/efeitos adversos , Antibacterianos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Comorbidade , Consenso , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Eosinofilia , Prova Pericial , Humanos , Leucocitose , Fígado/patologia , Fatores de Risco , Espanha/epidemiologiaRESUMO
OBJECTIVES: The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen (HLA) alleles, as well as killer immunoglobulin receptor (KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV-exposed seronegative (HESN) individuals. METHODS: A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV-infected partner admitting high-risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV-infected patients and 62 healthy controls. HLA class I and II alleles and KIR genotypes were assessed in genomic DNA from all individuals in the study by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) using bead array technology. RESULTS: HESN individuals showed a higher prevalence of HLA-A3 (62%) and HLA-B44 (83%) supertypes compared with HIV-infected individuals (42% and 66%, respectively). Regarding specific HLA alleles, HESN individuals had a higher prevalence of HLA-A*33:01, DRB1*04 and DQB1*03:02 alleles (14%, 34% and 31%, respectively) and a lower prevalence of the HLA-A*02:01 allele (27%) than HIV-infected patients (3%, 15%, 11% and 52%, respectively; P < 0.05). Interestingly, in a multivariate analysis, only the presence of DQB1*03:02 and the absence of A*02:01 alleles were independently associated with HESN status [odds ratio (OR) 3.4 (95% confidence interval (CI) 1.1-10.5) and 0.4 (95% CI: 0.1-0.9), respectively; P < 0.05]. No KIR genotype was associated with susceptibility to HIV infection. CONCLUSIONS: Our data showed that the presence of the HLA class II allele DQB1*03:02 was a correlate of immune protection against HIV infection, while the presence of the HLA class I allele A*02:01 was associated with being infected with HIV.
Assuntos
Predisposição Genética para Doença , Infecções por HIV/genética , Infecções por HIV/imunologia , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Cadeias beta de HLA-DQ/genética , Adulto , Idoso , Alelos , Estudos Transversais , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Receptores KIR/genética , EspanhaRESUMO
Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.
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Antivirais/uso terapêutico , Genótipo , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.
Assuntos
Antivirais/administração & dosagem , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Ribavirina/administração & dosagem , Terapia de Salvação/métodos , Tiazóis/administração & dosagem , Adulto , Idoso , Ácidos Aminoisobutíricos , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prolina/análogos & derivados , Quinolinas , Resultado do TratamentoRESUMO
Host-viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.
Assuntos
Hepatite C/genética , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Butirofilinas , Genótipo , Hepacivirus/genética , Hepatite C/virologia , Interações Hospedeiro-Patógeno/genética , Humanos , Família MultigênicaRESUMO
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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Hepatite C Crônica/epidemiologia , Antivirais/uso terapêutico , Saúde Global , Hepatite C Crônica/mortalidade , Hepatite C Crônica/terapia , Humanos , Incidência , Transplante de Fígado , Prevalência , Análise de SobrevidaRESUMO
The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Diagnósticos de Rotina/estatística & dados numéricos , Erradicação de Doenças , Quimioterapia Combinada/métodos , Feminino , Saúde Global , Hepatite C Crônica/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Adulto JovemRESUMO
The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Quimioterapia Combinada/métodos , Feminino , Saúde Global , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Adulto JovemRESUMO
CD4(+) regulatory T (T(reg)) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of T(reg) cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. T(reg) cells were defined as CD4(+)forkhead box P3 (FoxP3)(+). The percentage of T(reg) cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and T(reg) cell levels. Fewer than 50% of T(reg) cells expressed CD25, with differences in terms of CD127 expression between CD25(+) and CD25((-)) T(reg) cells. CD4(+)Foxp3(+) T(reg) cells displayed predominantly a central memory phenotype (CD45RA(-)CD27(+)), without differences between patients and healthy controls. Activated T(reg) cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated T(reg) cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients.
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Fatores de Transcrição Forkhead/análise , Infecções por HIV/imunologia , HIV , Hepacivirus , Hepatite C Crônica/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Estudos Transversais , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2/análise , Subunidade alfa de Receptor de Interleucina-7/análise , Ativação Linfocitária , Fenótipo , Estatísticas não Paramétricas , Adulto JovemRESUMO
Hepatitis E virus (HEV) is an enterically transmissible RNA agent that causes self-limited acute hepatitis. Recent reports have highlighted that organ-transplant recipients may develop chronic hepatitis E and progress to cirrhosis. Similar cases could occur in HIV patients. We have investigated 50 HIV-infected individuals with CD4 counts <200 cells/mm(3) and 43 with cryptogenic hepatitis. None of them showed HEV viremia. Thus, HEV infection does not seem to be prevalent in the HIV population and accordingly universal HEV vaccination is not warranted in these patients.
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Infecções por HIV/complicações , Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Contagem de Linfócito CD4 , Comorbidade , Humanos , PrevalênciaRESUMO
The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.
Assuntos
Infecções por HIV/complicações , Hepatite B/complicações , Hepatite C/complicações , Cirrose Hepática/diagnóstico , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade/métodos , Humanos , Prognóstico , Índice de Gravidade de DoençaRESUMO
Liver fibrosis progress slowly in patients with chronic hepatitis C and persistently normal alanine aminotransferase (PNALT) compared to subjects with elevated aminotransferases. Differences in liver fibrosis according to human immunodeficiency virus (HIV) status in this population have not been examined. All patients with serum hepatitis C virus (HCV)-RNA and PNALT who underwent liver fibrosis assessment using elastometry since 2004 at three different European hospitals were evaluated. Patients previously treated with interferon were excluded. PNALT was defined as ALT below the upper limit of normality in at least three consecutive determinations within the last 12 months. Fibrosis stage was defined as mild (Metavir F0-F1) if stiffness < or =7.1 kPa; moderate (F2) if 7.2-9.4 kPa; severe (F3) if 9.5-14 kPa, and cirrhosis (F4) if >14 kPa. A total of 449 HIV-negative and 133 HIV-positive patients were evaluated. HIV-negative patients were older (mean age 51.8 vs 43.5 years) and more frequently females (63%vs 37%) than the HIV counterparts. Mean serum HCV-RNA was similar in both the groups (5.9 vs 5.8 log IU/mL). Overall, 78.8% of the HIV patients were on HAART and their mean CD4 count was 525 (+/-278) cells/microL. In HIV-negatives, liver fibrosis was mild in 84.6%; moderate in 8.7%, severe in 3.3% and cirrhosis was found in 3.3%. In HIV patients, these figures were 70.7%, 18.8%, 6%, and 4.5%, respectively. In the multivariate logistic regression analysis, older age (odds ratio or OR: 1.04; 95% confidence interval or CI: 1.02-1.07; P < 0.001) and being HIV+ (OR: 2.6; 95% CI: 1.21-5.85; P < 0.01) were associated with severe liver fibrosis or cirrhosis (F3-F4). Thus, severe liver fibrosis and cirrhosis are seen in 6.6% of the HCV-monoinfected and in 10.5% of HCV-HIV co-infected patients with PNALT. Some degree of liver fibrosis that justifies treatment is seen in 15% of the HCV-monoinfected but doubles to nearly 30% in HIV-HCV co-infected patients with PNALT.
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Alanina Transaminase/sangue , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Técnicas de Imagem por Elasticidade , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soronegatividade para HIV , HIV-1/genética , HIV-1/isolamento & purificação , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Antígenos de Superfície da Hepatite B/sangue , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangueRESUMO
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes severe dysphagia and weight loss. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for the enteral nutrition of these patients. OBJECTIVES: To analyse mortality and complications in a series of patients diagnosed with ALS who underwent PEG, and to evaluate factors related to patient survival after the procedure. MATERIAL AND METHODS: We performed a prospective, observational study including all patients diagnosed with ALS and treated by our hospital's Gastroenterology Department in the period 1997-2013. We studied mortality, complications, and clinical and biochemical parameters, and correlated these with the survival rate. RESULTS: The study included a total of 57 patients, of whom 49 were ultimately treated with PEG. ALS onset was bulbar in 30 patients and spinal in 19. Mortality during the procedure and at 30 days was 2% (n = 1). Six patients (12.2%) experienced major complications; 17 (34.7%) experienced less serious complications which were easily resolved with conservative treatment. No significant differences were observed in forced vital capacity, albumin level, or age between patients with (n = 6) and without (n = 43) major complications. CONCLUSIONS: PEG is an effective, relatively safe procedure for the enteral nutrition of patients with ALS, although not without morbidity and mortality. Neither forced vital capacity nor the form of presentation of ALS were associated with morbidity in PEG.
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Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/mortalidade , Endoscopia , Nutrição Enteral , Gastrostomia , Esclerose Lateral Amiotrófica/terapia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , EspanhaRESUMO
The aims of the present study were to assess initial virological response (IVR) to adefovir (ADV) treatment for chronic hepatitis B, to identify patients with suboptimal response and to determine the incidence of ADV-resistant mutants. All patients treated with ADV for at least 12 months were evaluated for virological response and ADV resistance. IVR was defined as a reduction > or = 4 log10 IU/mL in hepatitis B virus (HBV)-DNA at month 6. Forty-two patients were analysed. Mean treatment duration was 23 +/- 7 months; 50% had prior lamivudine (LAM) therapy (LAM resistance 62%); 88% were hepatitis B e antigen (HBeAg)-negative; and 76% carried genotype D. IVR was seen in 40.5% of patients. Higher baseline ALT level was the only factor associated with IVR (P = 0.043). Patients with IVR achieved undetectable HBV-DNA at month 12 in 77% of cases compared with only 5% of those without IVR (P < 0.001). Five (12%) patients developed ADV-resistant mutations: rtN236T in four cases and one case with an rtV207L change, which has not been previously reported. This mutation was accompanied by viral rebound and alanine aminotransferase (ALT) flare. The cumulative probability of ADV-resistant mutations at 12 and 24 months was 5% and 17% respectively. IVR defined as a reduction > or = 4 log10 IU/mL in HBV-DNA at month 6 is a useful tool to predict virological response at month 12 and to identify patients with suboptimal response to ADV. Cumulative probability of ADV resistance is higher than previously reported for nucleos(t)ide-naïve patients.
Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Organofosfonatos/uso terapêutico , Carga Viral , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/farmacologia , DNA Viral/sangue , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Resultado do TratamentoRESUMO
Ribavirin (RBV) exposure is important for maximizing the response to chronic hepatitis C virus (HCV) therapy. However, RBV-associated haemolytic anaemia may force dose reductions or even treatment discontinuation. The use of zidovudine might further increases the risk of anaemia in HCV/HIV-coinfected patients. The predictors of anaemia were examined in PRESCO, a large trial conducted in HIV/HCV-coinfected patients treated with pegylated interferon alpha-2a 180 mug/week plus RBV 1000-1200 mg/day. Measurements included maximal decrease in haemoglobin (Hb) throughout treatment, drops in Hb to <10 (moderate) or to <8.5 g/dL (severe), and premature RBV discontinuation because of anaemia. Finally, the impact of anaemia on sustained virological response (SVR) was assessed. Moderate or severe anaemia occurred, respectively, in 51 (13%) and 13 (3.3%) of 389 patients included in the study. Lower baseline Hb [RR: 0.14 (95% CI 0.07-0.27); P < 0.0001] and greater Hb drops during the first 4 weeks of therapy [RR: 4.74 (95% CI 2.95-7.60); P < 0.0001] were independent predictors of moderate anaemia at any time point in the multivariate analysis. Mean drops in Hb from baseline to week 4 were significantly greater in patients receiving zidovudine compared with other drugs (-3.09 vs-2.3 g/dL; P < 0.001). Lower baseline Hb [RR: 0.33 (95% CI 0.11-0.95); P = 0.04] and maximal Hb drops during treatment [RR: 2.48 (95% CI 1.33-4.59); P = 0.004] predicted treatment discontinuation because of anaemia. However, maximal Hb drops, development of moderate-severe anaemia and RBV dose reductions were comparable among patients who achieved SVR and those who did not. Lower baseline Hb predicts maximal drops in Hb and development of anaemia in HIV/HCV-coinfected patients treated with pegylated interferon plus RBV. The use of zidovudine is associated with greater Hb declines at week 4. However, severe anaemia is relatively infrequent and seems not to have much impact on SVR. Given the availability of alternative antiretroviral drugs, it is advised to avoid zidovudine while receiving anti-HCV treatment.
Assuntos
Anemia/epidemiologia , Antivirais/efeitos adversos , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Biomarcadores , Quimioterapia Combinada , Feminino , Hemoglobinas/análise , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Análise Multivariada , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Estudos Prospectivos , Proteínas Recombinantes , Ribavirina/administração & dosagem , Resultado do Tratamento , Suspensão de Tratamento , Zidovudina/efeitos adversos , Zidovudina/uso terapêuticoRESUMO
SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.
Assuntos
Antivirais , Infecções por HIV/complicações , Hepacivirus , Hepatite C Crônica , Interferon-alfa , Polietilenoglicóis , Ribavirina , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1 , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Itália , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Espanha , Resultado do TratamentoRESUMO
Previous studies have demonstrated a high prevalence of seropositivity to the Ani s 1 protein in dyspeptic patients with Helicobacter pylori infection, but it is not known whether this represents episodes of anisakiasis misdiagnosis or previous exposure to the parasite without clinical relevance. To investigate the clinical significance of seropositivity to the Ani s 1 protein, a cohort study was performed with 87 consecutive dyspeptic patients who were treated for H. pylori infection. Fourteen (16.5%) patients were seropositive for the Ani s 1 protein, which was associated with the consumption of uncooked fish (p 0.0002). There were no differences in histological findings between subjects seropositive or seronegative for Ani s 1, but seropositive patients had increased eosinophil and basophil leukocyte counts (p < 0.05). Anti-Ani s 1 IgE was associated with a lack of improvement in the group of patients with non-ulcer dyspepsia after successful eradication of H. pylori (p 0.016). Thus, in at least a subset of patients with H. pylori infection, seropositivity to Ani s 1 could have clinical relevance. In addition, these data highlight that only anisakiasis associated with severe allergic or gastric symptoms is currently being diagnosed.
Assuntos
Alérgenos/sangue , Anisaquíase/microbiologia , Anisaquíase/parasitologia , Proteínas de Ligação ao Cálcio/sangue , Dispepsia/microbiologia , Dispepsia/parasitologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/parasitologia , Proteínas de Helminto/sangue , Adulto , Idoso , Antibacterianos/uso terapêutico , Biópsia , Estudos de Coortes , Diagnóstico Diferencial , Dispepsia/tratamento farmacológico , Endoscopia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/crescimento & desenvolvimento , Histocitoquímica , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. OBJECTIVE: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided
ANTECEDENTES: El síndrome DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) es una reacción cutánea grave inducida por hipersensibilidad a fármacos, compleja y multisistémica. Su diagnóstico y manejo es difícil e implica a diferentes especialistas. Es muy importante una correcta identificación del fármaco responsable para que el paciente disponga de opciones terapéuticas seguras en el futuro. No hay guías ni documentos de consenso españoles previos sobre el síndrome DRESS. OBJETIVO: Realizar una revisión y guía sobre el diagnóstico clínico y alergológico, manejo, tratamiento y prevención del DRESS según la evidencia científica disponible y la experiencia de expertos de diferentes especialidades médicas. MÉTODOS: Esta guía ha sido elaborada por un grupo de alergólogos del Comité de Alergia a Fármacos de la SEAIC, junto a otros especialistas involucrados en el manejo del DRESS e investigadores del Consorcio PIELenRed. Se realizó una búsqueda de publicaciones científicas sobre DRESS y el grupo de expertos evaluó la evidencia científica de la literatura y aportaron grados de recomendación. Cuando no existía evidencia se alcanzó un consenso entre expertos. RESULTADOS: Se publica la guía española sobre DRESS. Incluye aspectos prácticos importantes sobre el diagnóstico clínico, la identificación de fármacos causales a través del algoritmo del Sistema Español de Farmacovigilancia y guía para el diagnóstico alergológico. Se realizan recomendaciones sobre el manejo, tratamiento y prevención del DRESS. Se aportan algoritmos sobre el manejo en la fase aguda y en la de recuperación. Se ha elaborado una guía terapéutica escalonada consensuada por expertos especialistas implicados en el tratamiento del DRESS
Assuntos
Humanos , Síndrome de Hipersensibilidade a Medicamentos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/prevenção & controle , Síndrome de Hipersensibilidade a Medicamentos/terapia , EspanhaRESUMO
To assess the impact of chronic viral liver disease (CVLD) on hospital admissions and death in HIV-infected patients since the introduction of highly active antiretroviral therapy, all hospital charts, from January 1996 to December 2000, in a large HIV/AIDS reference center in Madrid were reviewed. Discharge diagnosis, complications during the inpatient period, and number and causes of death were recorded. A total of 1334 hospital admissions involving 875 HIV-infected individuals was recorded. Up to 82% of them were either active or former intravenous drug users. Overall, 158 (11.8%) were admitted because of complications of CVLD, or developed complications of CVLD during their admission for another reason. The absolute number and proportion of admissions caused by CVLD increased over time, from 9.4% (31 of 330) in 1996 to 16% (46 of 287) in 2000 (p < 0.05). Likewise, the total number and proportion of deaths due to CVLD increased from 9.3% (5 of 54) in 1996 to 45% (9 of 20) in 2000 (p < 0.05). Chronic hepatitis C was the only etiology in nearly three-quarters of patients who were admitted or died of CVLD. In conclusion, the proportion of hospital admissions caused by liver failure in HIV-infected patients has increased in the last 5 years, accounting for 16% of cases in 2000. End-stage liver disease currently represents 45% of causes of in-hospital death among HIV-infected individuals. Therefore, strategies to prevent infection by hepatitis viruses (hepatitis B vaccine) and specific treatment (interferon plus ribavirin for hepatitis C virus) should be encouraged among HIV-infected persons.
Assuntos
Infecções por HIV/complicações , Hepatite Viral Humana/mortalidade , Hospitalização/estatística & dados numéricos , Adulto , Doença Crônica , Feminino , Humanos , MasculinoRESUMO
The life expectancy of HIV-infected persons has extended significantly since the introduction of highly active antiretroviral therapies. Although classical opportunistic infections are now rarely seen, the toxicity of antiretroviral drugs as well as liver disease caused by hepatitis viruses represent an increasing cause of morbidity and mortality among HIV-positive persons. Since the rate of hepatitis C virus (HCV) infection is high among HIV carriers (up to 75% among intravenous drug users), HCV/HIV coinfection is widely prevalent. Predisposing liver damage favors a higher rate of hepatotoxicity of antiretroviral drugs, which can limit the benefit of HIV treatment in some individuals. Overall, severe hepatotoxicity appears in around 10% of subjects who began triple combinations including either protease inhibitors or non-nucleosides. The progression to cirrhosis seems to occur faster in the setting of HIV infection, and conversely recent data demonstrate that HCV infection can accelerate the progression to AIDS in HIV-positive persons. Although clinicians have been reluctant to treat hepatitis C in HIV-infected people, this therapeutic nihilism is unwarranted. The availability of new more successful regimens to treat hepatitis C, in particular using the new pegylated forms of interferon in combination with ribavirin, open new hopes for the care of HIV-HCV-coinfected persons.