RESUMEN
BACKGROUND: To evaluate whether dedicated access surgeons might have a significantly higher risk of acquiring hepatitis C infection compared to other vascular surgeons by assessing the prevalence of hepatitis C patients who are on chronic hemodialysis and to compare the frequency to patients undergoing elective vascular interventions. PATIENTS AND METHODS: A retrospective chart and data analysis of all patients on chronic hemodialysis was conducted. As a comparative group, the prevalence of anti-HCV antibodies and positive HCV RNA PCR among patients admitted for elective vascular surgery was assessed. RESULTS: Of 285 patients on chronic hemodialysis, 202 (71%) were had both tests (antibody test for HCV and specific HCV RNA PCR testing). 5% (n = 11; CI 95 = 3-10%) were antibody positive, and 4% (n = 8; CI 95 = 2-8%) were also PCR positive and therefore infectious. One patient was acutely infected. Of 4963 vascular surgical patients, 1141 (23%) had an anti-HCV antibody ELISA test and specific HCV RNA PCR testing. 0.4% (n = 4; CI 95 = 0.1-1%) were antibody positive and 0.2% (n = 2; CI 95 = 0.03-0.7%) were also PCR positive and hence infectious. No acutely infected patient was detected in this population. The chance of operating on a HCV positive and infectious patient among hemodialysis patients was almost 27 times higher than among elective vascular surgical patients (P < 0.0001; OR = 26.56; CI 95 = 5.42-253.40). CONCLUSIONS: Dedicated hemodialysis access surgeons have a higher risk to acquire hepatitis C infection compared to vascular surgeons performing all other elective vascular surgical interventions. To identify early infected surgeons operating on high risk HCV patient collectives and to start rapid treatment, PCR testing at regular intervals would be advisable.
Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Hepatitis C/transmisión , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Enfermedades Renales/terapia , Diálisis Renal , Procedimientos Quirúrgicos Vasculares/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Electivos , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/cirugía , Anticuerpos contra la Hepatitis C/sangre , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , ARN Viral/sangre , Estudios Retrospectivos , Medición de Riesgo , Recursos HumanosRESUMEN
Prediction of treatment response is clinically important in chronic hepatitis C virus (HCV) genotype 4 infection. Early viral kinetics is useful in this respect for genotype 1 but interpretation is dependent on assay linearity and reproducibility. The VERSANT HCV RNA 3.0 (bDNA-3.0) and the COBAS Amplicor HCV Monitor 2.0 (HCM-2.0) have been widely used quantitative assays. We wanted to comparatively evaluate the two tests in a large genotype 4 sample. Genotyping was performed by NS5b sequencing. Viral load was tested in parallel in 32 patients at least six times on antiviral therapy with interferon alpha (IFNalpha). Totally, 198 samples within a quantitative range from undetectable to about 7 x 10(6) IU/mL (bDNA-3.0) were obtained and compared. Twenty-two samples with viral load above 500 000 IU/mL tested by HCM-2.0 were 1:100 diluted and retested. Quantitative values were fitted to a third order polynomial (M = 0.118303 + 1.07503 x V+ 0.0112128 x V(2) - 0.0055504 x V(3); M...HCM-2.0, V...bDNA-3.0, both log IU/mL) showing progressive nonlinearity of HCM-2.0 above 100 000 IU/mL but better clinical sensitivity with respect to bDNA-3.0. Dilution lead to a gain of at least a factor of 2.7 and thus, overestimation compared with bDNA-3.0. Deviation from linearity and overestimation upon dilution by HCM-2.0 are similar with HCV genotype 4, compared with other HCV genotypes. Differences in test performance were not detected for subtypes but for individual patients possibly related to specific quasi-species patterns. The interpretation of viral kinetic data becomes difficult due to overestimation upon dilution of baseline values by HCM-2.0.
Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , ARN Viral/sangre , Genotipo , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Polietilenglicoles , Reacción en Cadena de la Polimerasa , ARN Viral/química , ARN Viral/genética , Proteínas Recombinantes , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Estadísticas no Paramétricas , Carga Viral/métodos , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genéticaRESUMEN
Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG-IFN-alpha-2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN-alpha-2a (days 0 and 1), and before and during weekly 180 microg PEG-IFN-alpha-2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty-eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV-RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN-alpha-2a was greater in virological responders (1.05 log [0.25-1.67]) than in nonresponders (NR) (0.34 [0.14-0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG-IFN-alpha-2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG-IFN-alpha-2a is different to that on standard IFN. In spite of a lower initial response PEG-IFN-alpha-2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Carga Viral , Adulto , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/fisiología , Hepatitis C Crónica/genética , Hepatitis C Crónica/inmunología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
Only 30% of patients with chronic hepatitis C virus genotype 1 (HCV-1) infection achieve a sustained virological response to interferon and ribavirin combination therapy. We prospectively assessed decline in viral load 24 h after one dose of interferon alfa as a predictor of non-response to 6 months of treatment with interferon and ribavirin. Interferon sensitivity was measured before initiation of combination therapy. We measured viral load in 29 consecutive patients, who had not previously been treated with interferon and who were chronically infected with HCV-1 within 24 h after one dose of 5 MU or 10 MU interferon alfa-2b, and 14 days of daily 5 MU interferon alfa-2b. A 24 h viral load decline by less than 70% of baseline after 5 MU interferon was the best pretreatment measure to identify non-responders (specificity 100%, n=10, 95% CI 74-100], sensitivity 83% [15/18], 59-96]).
Asunto(s)
Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Esquema de Medicación , Farmacorresistencia Microbiana/genética , Quimioterapia Combinada , Genotipo , Humanos , Interferón-alfa/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/administración & dosificación , Carga ViralRESUMEN
OBJECTIVE: To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders. STUDY DESIGN: 304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months. MAIN OUTCOME MEASURES: Virological response at end of treatment and 6 months thereafter. SETTING: University hospitals and tertiary referral centres. RESULTS: At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA. CONCLUSIONS: A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , ARN Viral/análisis , Ribavirina/administración & dosificación , Adulto , Anciano , Secuencia de Bases , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/diagnóstico , Humanos , Interferones/administración & dosificación , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Organización y Administración , Reacción en Cadena de la Polimerasa , Probabilidad , Estudios Prospectivos , Valores de Referencia , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Acute phase serum samples from 23 patients with Mycoplasma pneumoniae pneumonia were examined for specific antibodies with microparticle agglutination (MAG)-assay, complement fixation (CF)-test, IgM-specific ELISA, and Immunocard-based IgM-EIA. A novel 3-h IgA-ELISA (SeroMP-IgA) was tested to assess its diagnostic value. For MAG, CF, IgM-ELISA, card-based IgM-EIA, and IgA-ELISA positive results were obtained in 87%, 87%, 91%, 87%, and 100%, respectively. Overall concordance was 78%. Specificity testing of 46 healthy blood donors revealed an optimal diagnostic cut-off range of 22-30 IgA-ELISA binding units (BU)/mL resulting in 91%-100% specificity and 100%-96% sensitivity for serologic diagnosis of acute M. pneumoniae infection.
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Anticuerpos Antibacterianos/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunoglobulina A/sangre , Mycoplasma pneumoniae/inmunología , Neumonía por Mycoplasma/diagnóstico , Adolescente , Adulto , Niño , Humanos , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Especificidad de la EspecieRESUMEN
We prospectively monitored 74 consecutive allogeneic and 50 autologous patients after bone marrow/stem cell transplantation from May 1999 to October 2000 at our institution with quantitative CMV PCR and pp65 antigen assay once weekly from conditioning therapy to days 120 and 80 after transplantation, respectively. Written informed consent was obtained from every patient. CMV prophylaxis consisted of acyclovir during transplant. Additionally all patients received only platelet products from CMV-negative donors. In the case of CMV infection preemptive therapy with gancyclovir was applied. In the case of CMV disease high-dose immunoglobulin was given as well. In the allogeneic setting 16 out of 74 (22%) patients developed a positive PCR. Seven episodes of a positive pp65 antigen assay occurred in six allograft recipients. In the autologous setting no positive assay was found during the whole observation period. Additionally, in 6/16 patients a lymphoproliferative assay was performed during CMV infection. Two patients showed a positive (15 and 5.4) and four a negative (2,1.6,1,1.8) stimulation index.
Asunto(s)
Antígenos Virales/sangre , Trasplante de Médula Ósea , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , ADN Viral/sangre , Trasplante de Células Madre Hematopoyéticas , Fosfoproteínas/sangre , Reacción en Cadena de la Polimerasa/métodos , Proteínas de la Matriz Viral/sangre , Viremia/diagnóstico , Adolescente , Adulto , Antivirales/uso terapéutico , Biomarcadores , Trasplante de Médula Ósea/mortalidad , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/prevención & control , Femenino , Ganciclovir/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Huésped Inmunocomprometido , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Viremia/sangre , Viremia/etiologíaRESUMEN
BACKGROUND: Although specific therapy is available with ganciclovir, cytomegalovirus (CMV) disease remains a major problem after renal transplantation especially in CMV seronegative recipients of organs of seropositive donors (D+R-). METHODS: In an open-labeled prospective controlled trial we evaluated the effect of long-term oral ganciclovir prophylaxis (3 g/day for 3 months posttransplantation) in a cohort of 31 CMV-high risk (D+R-) renal transplant recipients (GC) compared with a cohort of 28 high-risk patients with targeted CMV prophylaxis (CO) receiving i.v. ganciclovir during antirejection therapy. Primary end-points were CMV infection, diagnosed by pp65 antigenemia assay or serologic method, and CMV disease. Additionally severity of CMV disease quantified by a scoring system was evaluated. RESULTS: CMV prophylaxis significantly reduced the incidence of CMV infection (CO: 75%, GC: 45%; P<.05) and CMV disease (CO: 60%, GC: 29%; P<.05) without relevant side effects and without any clinical suspicion of ganciclovir resistance. Severity of CMV disease as quantified by a scoring system was reduced from 8.3+/-6.7 points in controls to 3.3+/-2.6 points in ganciclovir-treated patients (P<.05). Mortality did not differ significantly between the two groups (CO: n=3, GC: n=1; NS). However, there was one lethal CMV disease and a second death possibly attributable to CMV disease in the control group, whereas in ganciclovir-treated patients there was no CMV-associated fatal outcome. CONCLUSION: Long-term oral ganciclovir prophylaxis is effective and safe in CMV high-risk renal transplant recipients.
Asunto(s)
Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/administración & dosificación , Trasplante de Riñón , Administración Oral , Adulto , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/mortalidad , Femenino , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia , Factores de TiempoRESUMEN
UNLABELLED: This trial investigated the efficacy of a combination of high-dose interferon-alpha (IFN-alpha) with ribavirin in IFN nonresponders. STUDY PROTOCOL: 304 patients with chronic hepatitis C were treated with 5 MU IFN-alpha2b (IntronA(R), Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW for each 3 months) alone (group A) or in combination with ribavirin (1-1.2 g per day) (group B). ALT was measured in monthly intervals, HCV-RNA in 3 monthly intervals. Pretreatment characteristics of the randomized patients were as follows: group A, n = 76; m/f, 54/22; 16% cirrhosis, age, 45. 7 +/- 12 years; ALT (U per litre), 66 +/- 35; group B, n = 81; m/f, 57/24; 17% cirrhosis, age, 48.2 +/- 12; ALT, 71 +/- 40. After 9 months of treatment, nine (11.6%) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in group A and 15 in group B. Six months after treatment only two patients in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT and no detectable HCV-RNA in serum. In addition to the well-known side-effects of IFN the mean haemoglobin concentration dropped by 2 g per litre in group B. These data indicate that a combination of high-dose IFN with ribavirin is effective in inducing a short-lasting complete response in one-third of IFN nonresponders. Prolonged treatment with IFN/ribavirin may be necessary to obtain a sustained response.