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Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.
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INTRODUCTION: New Delhi metallo-ß-lactamase producing Klebsiella pneumoniae (NDM-Kpn) strains have been causing healthcare-associated infections worldwide. The aim of this study was to describe the molecular mechanisms of antimicrobial resistance and to analyze the clonality of NDM-Kpn isolates collected between January 2019 and June 2020 from patients admitted to hospitals from the Lazio region, Italy. METHODS: We performed a retrospective cohort study. Whole-genome sequencing (WGS) was performed on all NDM-Kpn strains; clonality and genetic relationships were further investigated. RESULTS: During the surveillance period, 17 NDM-Kpn isolates were obtained from 17 patients admitted to seven different hospitals. Eight different sequence types (STs) were detected: ST147 (n = 4), ST383 (n = 4), ST15 (n = 3), ST11 (n = 2), ST17 (n = 1), ST29 (n = 1), ST307 (n = 1) and the newly identified ST4853 (n = 1). Genetic relationships were further investigated by the WGS-based core genome MLST (cgMLST) scheme, and 5 cluster types (CTs) were identified. Whereas a substantial overall heterogeneity among isolates was detected (8 different STs were identified out of 17 isolates), the strains within each cluster showed a very high level of genome similarity. DISCUSSION: Our study highlights the key role of surveillance, which allowed taking a picture of a part of the NDM-Kpn strains circulating in Italy, adding further insight into their molecular features.
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OBJECTIVES: Clostridioides difficile infection (CDI) represents a challenging issue, with an evolving epidemiology. Main objectives of our study were: to assess the frequency of diarrhea of overall etiology, including CDI, as a cause of hospital admission or occurring during hospital stay;- to determine the rate of underdiagnosis of community-acquired (CA-), health care associated (HCA)- and hospital onset (HO-) CDI, and explore factors associated with its clinical suspicion by physicians. METHODS: A prospective cohort study included all hospitalized patients with diarrhea at two acute-care hospitals. C. difficile (CD) tests were performed on every stool samples, irrespective of the treating physician request. Factors associated with the likelihood of CD test request by physicians were assessed. RESULTS: We enrolled 871 (6%) patients with diarrhea. CD test performed on all diarrheic stool samples was positive in 228 cases (26%); 37, 106, 85 cases of CA- (14%), HCA- (42%) and HO- diarrhea (24%), respectively. Treating physicians did not request CD test in 207 (24%) diarrhea cases. The rate of CDI underdiagnosis was 11% (24/228); it was higher in CA-CDI (27%, 10/37). Logistic regression analysis identified age >65 years (RR 1.1; 95 CI 1.06-1.2) and hospitalizations in the previous 3 months (RR 1.2; 95% CI 1.1-1.3) as independent factors associated with the likelihood of requesting the CD test by the physician. These risk factors differed by epidemiological classification of diarrhea and by hospital. CONCLUSIONS: Our study confirmed the relevance of CDI underdiagnosis and provided new insights in the factors underlying the lack of CDI clinical suspicion.
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Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Diarreia/diagnóstico , Diarreia/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a Trojan Horse Strategy. To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized in vitro. Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases.
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Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).
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Endocardite/epidemiologia , Infecções Relacionadas à Prótese/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/microbiologia , Bactérias/isolamento & purificação , Endocardite/microbiologia , Endocardite/mortalidade , Endocardite Bacteriana , Feminino , Mortalidade Hospitalar , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Valva Mitral/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas , Estreptococos Viridans , Adulto JovemRESUMO
Back pain and spine tenderness over the involved spine segment are common clinical findings of a number of relative benign conditions. However, back pain may be the presenting symptom of vertebral metastases in patients with systemic cancer, including hepatocellular carcinoma, a not uncommon complication in HCV-HIV infected patients. We describe a case of a 51-year-old intravenous drug user with HIV and HCV co-infection who developed dorsal spondylodiscitis due to Pseudomonas aeruginosa, which improved following antibiotic therapy. Three months after the end of therapy, the patient referred recurrence of back pain. The MRI showed different vertebral lesions of the dorsal spine and costal arch which turned out to be hepatocellular carcinoma metastasis at the histological examination. The patient had never been treated with the interferon-ribavirine combination therapy because of a major depressive syndrome. Interferon-free regimens are urgently required for HIV-HCV coinfected patients, especially when interferon-based regimens are contraindicated.
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Infecções Oportunistas Relacionadas com a AIDS/complicações , Carcinoma Hepatocelular/complicações , Discite/microbiologia , Infecções por HIV/complicações , Hospedeiro Imunocomprometido , Neoplasias Hepáticas/complicações , Infecções por Pseudomonas/complicações , Neoplasias da Coluna Vertebral/complicações , Antibacterianos/uso terapêutico , Carcinoma Hepatocelular/secundário , Coinfecção , Diagnóstico Diferencial , Discite/diagnóstico , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa/isolamento & purificação , Recidiva , Fatores de Risco , Neoplasias da Coluna Vertebral/secundário , Abuso de Substâncias por Via Intravenosa/complicações , Resultado do TratamentoRESUMO
PATIENT: Male, 73 FINAL DIAGNOSIS: Salmonella typhimurium abscess of the chest wall Symptoms: - MEDICATION: Ciprofloxacin Clinical Procedure:- Specialty: Infectious Diseases. OBJECTIVE: Unusual clinical course. BACKGROUND: Non-typhoid Salmonella extra-intestinal infections usually develop in infants and in adult patients with pre-existing predisposing conditions. Blood stream infections and urinary tract infections are the most common clinical presentations, but other sites of infection may be involved as well. CASE REPORT: We describe a case of invasive salmonellosis caused by Salmonella typhimurium involving the chest wall in a 73-year-old man. The patient had suffered from gastroenteritis followed by left basal pneumonia with pleural effusion 7 weeks before. The CT scan of the chest wall showed a pericostal abscess with shirt-stud morphology near the left last cartilaginous arch. The abscess was surgically drained and patient was cured after a 40-day ciprofloxacin treatment. CONCLUSIONS: A review of the literature on extra-intestinal non-typhoid salmonellosis shows that pleuropulmonary and soft-tissue infections are uncommon. We argue that non-typhoid Salmonella might be considered as a possible cause of chest wall abscess in individuals with recent history of gastroenteritis complicated by pneumonia and pleural effusion.
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The aim of our study was to evaluate the presence of occult HCV infection in two settings of patients experiencing immunosuppression: patients with Human Immunodeficiency Virus (HIV) infection and those with onco-haematological disease. Sixty consecutive HIV-positive/anti-HCV-negative/HCV RNA-negative patients (HIV group) and 32 consecutive anti-HCV/HCV RNA negative patients with an onco-haematological disease first undergoing chemotherapy (Onco-haematological group) were enrolled. HCV-RNA was sought by real time RT-PCR in plasma and Peripheral Blood Mononuclear Cell (PBMC) samples obtained at enrolment and during follow-up, in the patients in the HIV group every three months and in those in the onco-haematological group at months 1 and 3 during chemotherapy and then every three months after treatment discontinuation. No plasma or PBMC sample collected at enrolment and during the follow-up in the HIV and onco-haematological groups was HCV RNA positive. The results of this study rule out the existence of occult HCV infection in patients with strong immunosuppression due to different conditions, HIV infection and onco-haematological diseases.
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Infecções por HIV/complicações , Infecções por HIV/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Hepatite C/complicações , Hepatite C/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
We describe the case of transmission of an HBsAg-negative hepatitis B infection to an immunosuppressed patient by plasma donation from an HBsAg-negative subject, but with very low serum HBV DNA (about 50 IU/ml) and five mutations in the major hydrophilic region of HBsAg.
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Transfusão de Componentes Sanguíneos/efeitos adversos , Portador Sadio/virologia , Antígenos de Superfície da Hepatite B/genética , Hepatite B/diagnóstico , Hepatite B/transmissão , Hospedeiro Imunocomprometido , Mutação de Sentido Incorreto , Idoso , Portador Sadio/diagnóstico , DNA Viral/sangue , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Carga ViralRESUMO
To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to ß-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >10(3) IU/ml (p<0.02), in those with HAI >6 (p = 0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p = 0.005) and ALT serum levels (p = 0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p = 0.001) and those with fibrosis score >2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R.â=â4.21, C.I. 95% = 1.08-16.43, p<0.05, for HAI >6; O.R. = 3.12, C.I. 95% = 1.17-8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression.
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Vírus da Hepatite B/fisiologia , Hepatite B Crônica/genética , Fígado/metabolismo , Fígado/virologia , MicroRNAs/genética , Adulto , DNA Viral/sangue , DNA Viral/metabolismo , Progressão da Doença , Feminino , Expressão Gênica , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carga Viral , Replicação ViralRESUMO
AIMS: To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. METHODS: Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). RESULTS: No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p < 0.05) and lower values of serum HBV DNA (1.77 × 10(6) ± 4.76 × 10(6) vs. 1.68 × 10(8) ± 5.46 × 10(8)). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B (p < 0.05). CONCLUSIONS: HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load may suggest that greater and/or more prolonged immune pressure might have induced their selection.
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Antivirais/administração & dosagem , Farmacorresistência Viral , Vírus da Hepatite B/isolamento & purificação , Hepatite B/tratamento farmacológico , Lamivudina/administração & dosagem , Mutação de Sentido Incorreto , DNA Polimerase Dirigida por RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Antivirais/farmacologia , DNA Viral/sangue , DNA Viral/química , DNA Viral/genética , Feminino , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Itália , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Carga Viral , Adulto JovemRESUMO
A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months.
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Antivirais/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite B/tratamento farmacológico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , DNA Viral/sangue , Feminino , Hepatite B/complicações , Hepatite B/virologia , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Carga Viral , Ativação ViralRESUMO
BACKGROUND: Two formulations of Pegylated interferon (Peg-IFN) are on the market for treatment of chronic hepatitis C virus (HCV) infection. The purpose of this meta-analysis was to assess the efficacy of Peg-IFN α-2a versus Peg-IFN α-2b in combination with ribavirin in anti-human immunodeficiency virus (HIV)-negative patients with genotype 1 chronic HCV infection. METHODS: The following criteria were to be met for inclusion in the meta-analysis: (a) original data from randomized and non-randomized clinical trials; (b) study on the efficacy of conventional doses of Peg-IFN α-2a (180 µg/week) versus Peg-IFN α-2b (1.5 µg/kg of body weight/week), both in combination with ribavirin, in antiviral therapy-naïve HCV-genotype 1 subjects; (c) at least one of these primary outcomes: Rapid Virological Response (RVR); Early Complete Virological Response (EVR); End of Treatment Response (ETR); Sustained Virological Response (SVR); (d) odds ratio estimates of relative risk (RR) and associated 95% confidence intervals (CIs) or at least data enabling them to be computed; (e) English language; and (f) published as a full paper up to December 2011. RESULTS: Seven published studies met the inclusion criteria, allowing a meta-analysis on 3,026 patients. Peg-IFN α-2a and Peg-IFN α-2b showed similar rate of RVR (RR = 1.05; 95% CI = 0.87-1.27, p = 0.62) and SVR (RR = 1.08; 95% CI = 0.99-1.18, p = 0.098). Peg-IFN α-2a more frequently than Peg-IFN α-2b achieved EVR (RR = 1.11; 95% CI = 1.02-1.21, p = 0.013) and ETR (RR = 1.22; 95% CI = 1.14-1.31, p < 0.0001). CONCLUSION: The standard schedules of Peg-IFN α-2a and Peg-IFN α-2b, both in combination with ribavirin, can be used indifferently for patients with chronic HCV genotype 1 who are anti- to eliminate HIV-negative and antiviral treatment-naïve.
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Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
Acute hepatitis C is often asymptomatic, frequently remains undiagnosed and frequently evolves to chronic hepatitis. Early, short-term interferon treatment is efficacious in acute hepatitis C, and so underscores the importance of an early diagnosis and the need to distinguish acute infection from acute exacerbation of chronic HCV infection. The gold standard for the diagnosis of acute hepatitis C is demonstration of conversion to anti-HCV positivity, HCV RNA positivity or both, events that frequently occur before the patient comes to medical attention. Several laboratory approaches to assist with early diagnosis of acute hepatitis C have been developed. Our studies, reviewed here, show that testing for antibody avidity and anti-HCV immunoglobulin M allow diagnosis in up to 90% of cases of acute hepatitis C.
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Afinidade de Anticorpos , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Imunoglobulina M/imunologia , Doença Aguda , Doenças Assintomáticas , Diagnóstico Precoce , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Imunoglobulina G/imunologia , RNA Viral/genéticaRESUMO
AIMS: To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients. PATIENTS AND METHODS: 8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naïve to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy. RESULTS: An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare. CONCLUSION: Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.
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Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Leucemia Linfocítica Crônica de Células B/virologia , Linfoma não Hodgkin/virologia , Idoso , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/fisiologia , Hepatite C/complicações , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Rituximab , Carga Viral , Replicação ViralRESUMO
The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation.
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Hepatite B/imunologia , Hepatite B/virologia , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Ativação Viral , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Antivirais/administração & dosagem , DNA Viral/sangue , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Carga Viral , ViremiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Anticorpos Anti-Hepatite C/imunologia , Hepatite C/imunologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Estudos de Coortes , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/imunologia , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de RiscoRESUMO
We report the case of a patient with non-Hodgkin's lymphoma who, during chemotherapy according to the r-CHOP schedule (rituximab-cyclophosphamide-doxorubicin-vincristine and prednisone), showed a hepatic flare with jaundice. Given the patient's state of asymptomatic carrier of HBsAg, we began a treatment of telbivudine (600 mg/die), resulting in a regression of hepatitis flare and negativization of HBV viraemia.
Assuntos
Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase Intra-Hepática/induzido quimicamente , Imunossupressores/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Humanos , Hiperbilirrubinemia/induzido quimicamente , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Pirimidinonas/uso terapêutico , Rituximab , Telbivudina , Timidina/análogos & derivados , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Viremia/complicações , Ativação ViralRESUMO
BACKGROUND: The gold standard for the diagnosis of acute hepatitis C (AHC) is seroconversion to anti-HCV/HCV-RNA positivity, an occurrence frequently missed in clinical practice. OBJECTIVES: This study aims to diagnose AHC by the combined use of the HCV Avidity Index (HCV-AI) and HCV-IgM titre. STUDY DESIGN: We enrolled 45 patients with AHC diagnosed by seroconversion to anti-HCV/HCV-RNA positivity and 36 with exacerbation of chronic hepatitis C (e-CHC) diagnosed at least 1 year earlier. HCV-IgM titres were determined by a commercial enzyme-linked immunosorbent assay (ELISA) and HCV-AI by an ELISA for detection of HCV IgG with a partial modification. For each test, specific cut-off values at four selected checking points were established during the observation (<10 days, 11-15 days, 16-20 days and >20 days from the onset of symptoms): for the HCV-IgM assay, the highest value in e-CHC +5% and for HCV-AI assay, the lowest value in e-CHC -5%. RESULTS: Around 90% of patients with AHC or e-CHC were correctly diagnosed at all checking points by combining the results of both tests. This practice afforded an improvement in sensitivity for the diagnosis of AHC, with the highest values at first and third checking points (92.3% and 92.6%, respectively) and an improvement in negative predictive value (NPV), with the highest value at first checking point (92.6%). CONCLUSIONS: The diagnosis of AHC, made by seroconversion to anti-HCV/HCV-RNA positivity, was confirmed in more than 90% of patients by combining the results of IgG Avidity Index (IgG-AI) and HCV-IgM obtained in a single serum sample.
Assuntos
Anticorpos Antivirais/sangue , Afinidade de Anticorpos , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Algoritmos , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Hepacivirus/imunologia , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Curva ROC , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: The impact of hepatitis B virus (HBV) superinfection in hepatitis C virus (HCV) chronic carriers was evaluated in a long-term follow-up study on 29 chronic anti-HCV carriers with acute hepatitis B (AVH-B) (Case group BC) and 29 anti-HCV negative patients with AVH-B (Control group B), pair-matched for age (+/-5 years), sex, and risk factors for the acquisition of HBV infection. Patients in Case group BC and those in Control group B showed similar initial HBV viral load and a similar trend of becoming negative for HBV-DNA. AVH-B showed a severe course more frequently in Case group BC than in Control group B (34.5% versus 6.9%, P < 0.05). Of the 28 patients in Case group BC alive at the end of the acute illness (one death from liver failure), 24 were followed up for 2-6 years, median 5 years: 22 patients became HBsAg-negative and two progressed to HBsAg-positive chronic hepatitis. HCV-RNA was undetectable in all patients during AVH-B; in the 24 patients with a long-term follow-up, HCV-RNA was detected in seven (29.2%) after 1 year, in 14 (58.3%) after 2 years, and in 18 (75%) after 3-6 years. The six patients who eradicated chronic HCV infection, compared with 18 showing reactivation of HCV replication, had higher values of aspartate aminotransferase and alanine aminotransferase and a higher prevalence of cases with severe AVH-B (83.3% versus 22.2%, P < 0.05). CONCLUSIONS: Although it can be life-threatening, HBV superinfection in HCV chronic carriers may lead to clearance of chronic HCV infection, especially in patients with severe AVH-B.