Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort.

Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post-treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2 . In conclusion, eGFR slightly declines during therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR.

Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection.

OBJECTIVE: The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens. PATIENTS AND METHODS: From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ. RESULTS: A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and ≥LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004. CONCLUSIONS: TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting.

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients.

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

[Massive venous thrombosis with cardiac invasion as primary manifestation of hepatocarcinoma]. / Trombosis venosa masiva con invasión cardiaca como primera manifestación de un hepatocarcinoma.

Hepatocellular carcinoma has a tendency to invade vascular structures. However, extension into the hepatic veins or heart is uncommon. We describe the case of a 68 years old man with chronic viral hepatitis type C, consulting about edema and pain in his left leg. Doppler scan showed deep venous thrombosis in that level and computed tomography of thorax and abdomen showed complete thrombosis of the inferior cava vein, thrombosis of the left suprahepatic vein, a voluminous thrombus in the right atrium and an irregular mass in the liver. Alpha-fetoprotein was 77,046 ng/ml The biopsy of the rigth atrium thrombus demonstrated diseminated hepatocellular carcinoma. We comment the patient progress after surgery, the incidence, clinical symptoms, and therapy options for these patients.

Trombosis venosa masiva con invasión cardiaca como primera manifestación de un hepatocarcinoma / Hepatocellular involving vascular structures and heart: diagnosis and treatment

El hepatocarcinoma tiene tendencia a invadir estructuras vasculares. Es infrecuente, sin embargo, la afectación de las venas hepáticas y las metástasis intracardíacas. Presentamos el caso de un varón de 68 años con hepatopatía crónica por virus C, que consulta por edema y dolor a nivel del miembro inferior izquierdo. Mediante eco doppler, se objetivó, trombosis venosa profunda a dicho nivel y el TAC tóraco-abdominal, mostró, trombosis completa de la vena cava inferior, trombosis de la vena suprahepática izquierda, un voluminoso trombo en aurícula derecha y una masa irregular en hígado. La alfafetoproteína fue de 77.046 ng/ml. La biopsia del trombo de aurícula derecha estableció el diagnóstico de hepatocarcinoma. Se comenta la evolución del paciente tras la intervención quirúrgica, la frecuencia y clínica de esta complicación y las posibilidades terapéuticas en estos pacientes (AU)

[Nosocomial bacteremia in the adult patient. Study of associated costs]. / Bacteriemia nosocomial en el paciente adulto. Estudio de costes asociados.

OBJECTIVE: Nosocomial infection causes a prolonged hospital stay and an increase in care costs. The objective of this study was to determine the length of stay excess and costs attributable to nosocomial bacteremia. PATIENTS AND METHODS: Retrospective study of clinical records of 148 patients with nosocomial bacteremia during 1996. A matched case-control study was performed. For matching, the following parameters were used: RDG, year of admission, age 10 years, main diagnosis and number of secondary diagnoses. Costs were determined by excess length of hospital stay and calculating alternative costs. RESULTS: Matching was obtained for 100 cases (67.5%) and cost estimation was performed. Compared with cases, non-matched cases showed differences regarding significant issues for cost, such as hospital stay ( p = 0.01), number of empirical (p = 0.001) or definitive antibiotics (p = 0.03). The median hospital stay for cases was longer than for controls (35 vs 15.5 days, respectively; p = 0.000). When only survivor case-control pairs were considered (n = 75), cases remained in hospital for a median of 36 vs 15 days for controls (p = 0.000). Hospital stay days attributable to nosocomial bacteremia were 19.5 for all matched and 21 for matched survivor cases. Only 76% of cases had stay days attributable to bacteremia. Significant differences between cases and controls included: the mean total costs of admission (p = 0.000), cost of stay (p = 0.001), pharmaceutical expenses (p = 0.000), and cost of microbiological studies (p = 0.000), laboratory work-up (p = 0.001) and radiological studies (p = 0.000). Hospital stay represented more than 60% of costs, followed by pharmaceutical expenses. Cost differences between bacteremic patients and controls, calculated in function of stay median, was 4.424 euros (p = 0.000) and 4.744 euros (p = 0.000) for alternative costs. Ten cases showed a difference that represented more than half of the total difference. CONCLUSIONS: Nosocomial bacteremia represent a stay prolongation and a significant economical burden. Hospital stay and pharmaceutical expenses accounted for the most part of the associated costs. The differences in costs obtained with both methods were small. Since not all selected cases were matched, there may be an error in the appreciation of the difference between cases and controls.

[Streptococcus bovis meningitis. An infrequent cause of bacterial meningitis in the adult patient]. / Meningitis por Streptococcus bovis: una causa poco frecuente de meningitis bacteriana en el paciente adulto.

INTRODUCTION: Bacterial meningitis in adult patients, produced by streptococci other than Streptococcus pneumoniae, is not common. CASE REPORT: We report the case of a 74 year old male patient with meningitis and endocarditis due to Streptococcus bovis (group D, not enterococcus), sensitive to penicillin (CMI< 0.1 mg/L), with no characteristic clinical or analytical discoveries. A gastrointestinal exploration revealed only diverticles in the colon and two lesions compatible with splenic infarction, observed by using computerised axial tomography of the abdomen. The patient responded favourably to a four week course of antibiotics; he remained asymptomatic, afebrile and culture negative after the therapy was stopped. CONCLUSIONS: In many previously reported cases, there is an association with gastrointestinal illness, endocarditis or oral lesions. Gram staining of the cerebrospinal fluid is usually negative and the neurological signs are often subtle. In the case of bacteraemia, endocarditis or S. bovis meningitis, the presence of an underlying pathology of the colon due to the frequent association between these processes must be ruled out. Treatment with penicillin G is usually sufficient.

Meningitis por Streptococcus bovis: una causa poco frecuente de meningitis bacteriana en el paciente adulto / Streptococcus bovis meningitis. An infrequent cause of bacterial meningitis in the adult patient

Introducción. La meningitis producida por estreptococos diferentes del S. pneumoniae es infrecuente en los pacientes adultos. Caso clínico. Paciente varón, de 74 años, que presentó meningitis y endocarditis debidas a Streptococcus bovis (grupo D, no enterococo), sensible a la penicilina (CMI< 0,1 mg/L), sin hallazgos clínicos ni analíticos característicos. En el estudio gastrointestinal sólo se observaron divertículos en el colon; mediante tomografía computarizada abdominal se observaron dos lesiones esplénicas compatibles con infarto. El paciente evolucionó favorablemente con el tratamiento antibiótico que recibió durante cuatro semanas, tras el cual permaneció asintomático, afebril y con hemocultivos negativos. Conclusiones. En muchos de los casos similares que se han comunicado coexiste una enfermedad gastrointestinal, endocarditis o lesiones orales. La tinción de Gram del líquido cefalorraquídeo suele ser negativa y los signos neurológicos son a menudo sutiles. En caso de bacteriemia, endocarditis o meningitis por S. bovis, es necesario descartar la presencia de patología colónica debido a la frecuente asociación entre estos procesos. El tratamiento con penicilina G es usualmente adecuado (AU)

[Paronychia in patients infected with HIV treated with indinavir]. / Paroniquia en pacientes infectados por el VIH tratados con indinavir.

A retrospective study of cases of paronychia associated with anti-retroviral therapy diagnosed in two general hospitals is here reported. Lesions appeared from 3 and 48 months after institution of therapy. At diagnosis, 84.6% of patients were on indinavir therapy. CD4 values ranged from 120 and 1,332 cells/mm3 and viral load was lower than 200 copies/ml in 92.3 of cases. Conservative therapy was applied in 7 patients and surgery in 6. In all patients indinavir therapy was discontinued, and cure was achieved 16 weeks later. The "retinoid" effect of indinavir is discussed as likely pathogenic explanation for this complications. We advocate for topic therapy and change of anti-retroviral therapy, reserving surgery for patients not responding to therapy. Pain and functional limitation caused by this non uncommon complication (1.6% of our patients treated with anti-retroviral agents) makes its knowledge necessary and an active search by clinicians in patients receiving indinavir therapy.

Paroniquia en pacientes infectados por el VIH tratados con indinavir / Paronychia in HIV-positive patients treated with indinavir

Presentamos un estudio retrospectivo de los casos de paroniquia, asociados a terapia antirretrovírica, diagnosticados en dos hospitales generales. Las lesiones aparecieron entre 3 y 48 meses desde el inicio de la terapia. El 84,6 por ciento de los pacientes se encontraban en tratamiento con indinavir en el momento del diagnóstico. La cifra de CD4 varió entre 120 y 1.332 cél/mm3 y la carga vírica fue inferior a 200 cop/ml en el 92,3 por ciento de los casos. Se realizó terapia médica conservadora en 7 pacientes y en 6 cirugía; en todos los casos se suspendió la terapia con indinavir, con lo que tras 16 semanas se consiguió la curación.Se discute el probable efecto retinoide-like del indinavir como probable explicación patogénica de esta complicación. Se preconiza la realización de terapia tópica y la modificación del tratamiento antirretrovírico, reservando la terapia quirúrgica para los casos refractarios. El dolor y la limitación funcional que produce esta complicación, no infrecuente (1,6 por ciento de nuestros pacientes tratados con antirretrovíricos), hace necesario su conocimiento y búsqueda activa por parte de los clínicos en los pacientes que reciben tratamiento con indinavir (AU)

[A management analysis of bacterial meningitis in a hospital emergency service: the delay from the start of treatment and related factors]. / Análisis del manejo de la meningitis bacteriana en un servicio de urgencias hospitalario: demora del inicio del tratamiento y factores relacionados.

OBJECTIVE: To establish the time elapsed from the patient arrival to the emergency room to the beginning of antibiotic therapy. To identify etiologic factors for treatment delay. METHODS: 73 patients diagnosed of bacterial meningitis in the emergency room and admitted to the hospital were studied. Patient characteristics as well as meningitis predisposing factors, symptoms, physical examination, laboratory data, radiological studies and previous ambulatory treatment, were recorded retrospectively. Arrival time, time expended at diagnostic procedures and time of administration of the first antibiotic dose, as well as the administration place were registered. Patients clinical evolution, and factors influencing the delay of antibiotic administration were analyzed. RESULTS: Median age was 17 years. Patient care was evenly distributed along the day, 80% had a light base risk, 29% had at least a risk factor for meningitis, 22% received antibiotic previously. Clinical presentation was classic in more than 71% of patients. Blood cultures were positive in 41%, and CSF cultures were positive in 63%, 43% of cases were related to Neisseria meningitidis, 20% Streptococcus pneumoniae and unknown bacteria in 31.5%. Computerized Tomography (CT) was performed in 9 cases. Median time from the arrival to the Emergency Room until antibiotic administration was 5 hours and 25 minutes: When antibiotics were given before Lumbar Puncture (LP), it was 2 hours and 50 minutes, 5 hours 20 minutes when therapy was started after LP, and 7 hours and 22 minutes when CT was performed before LP. The only factor showing a statistically significant relation with the time to antibiotic administration was the patient being sent by the primary care physician to the hospital with a presumptive diagnosis of bacterial meningitis (1 hour 20 minutes vs. 5 hours 51 minutes). CONCLUSION: Only a small part of bacterial meningitis cases start antibiotic treatment in the first 30 minutes. Delay is high and it increases when certain diagnostic tests are performed. Information received from the primary care physician, has the highest influence on the beginning of treatment.

Pasteurella spp: un nuevo germen causante de tiroiditis aguda supurada / Pasteurella spp: a new microorganism adding to acute suppurative thyroiditis etiology

La tiroiditis aguda supurada es una entidad poco frecuente debido a la resistencia natural de la glándula a la infección. Patología preexistente sobre el tiroides así como defectos anatómicos locales predisponen a padecer la enfermedad. Presentamos el primer caso descrito en la literatura por Pasteurella spp tras infección de vías respiratorias superiores, con clínica poco florida mimetizando tiroiditis subaguda. La evolución fue satisfactoria tras drenaje quirúrgico (AU)

Análisis del manejo de la meningitis bacteriana en un servicio de urgencias hospitalario: demora del inicio del tratamiento y factores relacionados / Handling of bacterial meningitis on a hospital emergency room: delays at the beginning of treatment and related factors

Fundamento. Conocer el tiempo de retraso en la administración de antibióticos en la meningitis bacteriana desde la llegada del paciente al servicio de urgencias e identificar los factores que muestran relación con el mismo. Métodos. Serie de 73 casos de pacientes con él diagnostico de meningitis bacteriana atendidos en el servicio de urgencias e ingresados en el hospital. Los datos se recogieron retrospectivamente. Se estudiaron las características de los pacientes, factores predisponentes para meningitis, clínica, exploración física, datos de laboratorio, estudios radiológicos y tratamiento ambulatorio previo. Tiempos de llegada, de realización de los procedimientos diagnósticos y de administración de la primera dosis de antibiótico y lugar de administración. Se recogió la evolución de los pacientes y se analizaron los factores que influyeron en la demora de la administración de antibióticos. Resultados. La mediana de edad fue de 17 años, la atención a los pacientes se repartió a lo largo de la jornada, el riesgo de base fue leve en el 80%, el 29% tuvo al menos un factor de riesgo para meningitis, el 22 porciento recibió antibiótico ambulatoriamente, la presentación clínica fue la clásica en mas del 71% de los pacientes. El hemocultivo fue positivo en 41% y el cultivo de LCR en el 63 porciento. El 43% de los casos fueron debidos a Neisseria meningitidis, 20% Streptococcus pneumoniae y a germen desconocido en el 31,5 porciento. Se realizaron 9 Tomografías axiales computarizadas (TAC). El tiempo medio desde la llegada al servicio de urgencias hasta la administración de antibióticos fue de 5 horas y 25 minutos. Cuando se administró antes de la punción lumbar fue de 2 horas 50 minutos; de 5 horas 20 minutos; cuando se administró después de la punción lumbar y de 7 horas 22 minutos cuando se realizo TAC cerebral antes de la punción. El único factor que demostró relación estadísticamente significativa con la demora en la administración de antibiótico fue el hecho de que el paciente fuese remitido por su medico de cabecera con sospecha de meningitis bacteriana (1 hora 20 minutos vs 5 horas 51 minutos). Conclusiones. Sólo en una pequeña parte de los casos de meningitis bacteriana se inicia el tratamiento antibiótico en los primeros 30 minutos. La demora media es elevada y aún más cuando se realizan determinadas pruebas diagnósticas (AU)

[Pasteurella spp: a new microorganism to the cause of acute suppurative thyroiditis]. / Pasteurella spp: un nuevo germen causante de tiroiditis aguda supurada.

Acute suppurative thyroiditis is an uncommon disease due to local resistance of the gland to infection. Preexisting gland pathology and local anatomic abnormalities are predisposing factors. We present the first case described in the medical literature caused by Pasteurella spp after upper respiratory infection with insidious manifestations resembling subacute thyroiditis. The course was benign after surgical drainage.