Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Differences between childhood- and adulthood-onset eosinophilic esophagitis: An analysis from the EoE connect registry.

BACKGROUND: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce. AIM: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages. METHODS: Cross-sectional analysis of the EoE CONNECT registry. RESULTS: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001). CONCLUSIONS: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry.

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe.

BACKGROUND: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. METHODS: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. RESULTS: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. CONCLUSION: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe.

Efficacy and safety of cold versus hot snare polypectomy for small (5-9 mm) colorectal polyps: a multicenter randomized controlled trial.

BACKGROUND: Resection techniques for small polyps include cold snare polypectomy (CSP) and hot snare polypectomy (HSP). This study compared CSP and HSP in 5-9 mm polyps in terms of complete resection and adverse events. METHODS: This was a multicenter, randomized trial conducted in seven Spanish centers between February and November 2019. Patients with ≥ 1 5-9 mm polyp were randomized to CSP or HSP, regardless of morphology or pit pattern. After polypectomy, two marginal biopsies were submitted to a pathologist who was blinded to polyp histology. Complete resection was defined as normal mucosa or burn artifacts in the biopsies. Abdominal pain was only assessed in patients without < 5 mm or > 9 mm polyps. RESULTS: 496 patients were randomized: 237 (394 polyps) to CSP and 259 (397 polyps) to HSP. Complete polypectomy rates were 92.5 % with CSP and 94.0 % with HSP (difference 1.5 %, 95 % confidence interval -1.9 % to 4.9 %). Intraprocedural bleeding occurred during three CSPs (0.8 %) and seven HSPs (1.8 %) (P = 0.34). One lesion per group (0.4 %) presented delayed hemorrhage. Post-colonoscopy abdominal pain presented similarly in both groups 1 hour after the procedure (CSP 18.8 % vs. HSP 18.4 %) but was higher in the HSP group after 5 hours (5.9 % vs. 16.5 %; P = 0.02). A higher proportion of patients were asymptomatic 24 hours after CSP than after HSP (97 % vs. 86.4 %; P = 0.01). CONCLUSIONS: We observed no differences in complete resection and bleeding rates between CSP and HSP. CSP reduced the intensity and duration of post-colonoscopy abdominal pain.

Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry.

BACKGROUND: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown. AIMS: To assess the effectiveness of PPI therapy for EoE in real-world practice. METHODS: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses. RESULTS: Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4-9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3-5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype. CONCLUSIONS: Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term.

Limitaciones de la determinación de calprotectina fecal en pacientes con colitis ulcerosa y pólipos inflamatorios / Limitations of the determination of faecal calprotectin in patients with ulcerative colitis and inflammatory polyps

Introducción: La calprotectina en heces es una técnica útil para detectar actividad en pacientes con colitis ulcerosa. No obstante, puede haber valores elevados debido a otros factores distintos de la actividad de la colitis ulcerosa. Nuestro objetivo fue analizar posibles resultados falsos positivos de calprotectina para la actividad de la colitis ulcerosa debidos a la presencia de pólipos inflamatorios. Pacientes y métodos: Estudio retrospectivo, descriptivo y observacional. Se recogieron los datos de pacientes seguidos durante 2 años en los que se realizó una colonoscopia dentro de los 3 meses posteriores a detectarse valores de calprotectina elevados (>150μg/g) antes de modificar el tratamiento. Resultados: Se revisaron 39 pacientes y en 5 de ellos, previamente diagnosticados de colitis ulcerosa extensa, se detectaron pólipos inflamatorios. Tres pacientes tomaban mesalazina, uno azatioprina y otro estaba en tratamiento con infliximab. Todos ellos se encontraban asintomáticos y la endoscopia no presentaba actividad macroscópica (Mayo endoscópico=0) ni histológica. La mediana de los valores de calprotectina fue de 422μg/g (RIC: 298-2.408) y permanecieron elevados en una segunda determinación. En 4 de los pacientes los pólipos inflamatorios eran múltiples y de pequeño tamaño. Otro paciente presentaba un pólipo de 4cm. Discusión: En la práctica clínica podemos encontrar valores de calprotectina fecal elevados no debidos a la presencia de actividad de la colitis ulcerosa, sino a otras lesiones, como pólipos inflamatorios. Este hecho debe ser tenido en cuenta antes de llevar a cabo cambios relevantes como la subida de escalón terapéutico a inmunosupresores o biológicos en pacientes con elevación de calprotectina confirmada

Introduction: Faecal calprotectin is a useful technique for detecting activity in patients with ulcerative colitis. However, there may be high levels due to factors other than the activity of ulcerative colitis. Our aim was to analyse possible false positive results of calprotectin for the activity of ulcerative colitis owing to the presence of inflammatory polyps. Patients and methods: Retrospective, observational, descriptive study. Data was collected from patients monitored for 2 years in whom a colonoscopy had been requested within 3 months after detecting high calprotectin values (>150μg/g) and before modifying the treatment. Results: We reviewed 39 patients and in 5 of them, with previous diagnosis of extensive ulcerative colitis, inflammatory polyps were detected. Three patients were on treatment with mesalazine, one with azathioprine and other with infliximab. All of them were asymptomatic and the endoscopy did not show macroscopic activity (endoscopic Mayo score=0) or histological activity. The median values of calprotectin were 422μg/g (IQR: 298-2,408) and they remained elevated in a second measurement. In 4 of the patients the inflammatory polyps were multiple and small in size. The other patient had a polyp measuring 4cm. Discussion: In clinical practice we can find high faecal calprotectin levels not due to the presence of ulcerative colitis activity, but due to other lesions such as inflammatory polyps. This fact must be taken into account before carrying out relevant changes such as step-up therapy to immunosuppressive drugs or biological drugs in patients with confirmed high calprotectin levels

Limitations of the determination of faecal calprotectin in patients with ulcerative colitis and inflammatory polyps. / Limitaciones de la determinación de calprotectina fecal en pacientes con colitis ulcerosa y pólipos inflamatorios.

INTRODUCTION: Faecal calprotectin is a useful technique for detecting activity in patients with ulcerative colitis. However, there may be high levels due to factors other than the activity of ulcerative colitis. Our aim was to analyse possible false positive results of calprotectin for the activity of ulcerative colitis owing to the presence of inflammatory polyps. PATIENTS AND METHODS: Retrospective, observational, descriptive study. Data was collected from patients monitored for 2 years in whom a colonoscopy had been requested within 3 months after detecting high calprotectin values (>150µg/g) and before modifying the treatment. RESULTS: We reviewed 39 patients and in 5 of them, with previous diagnosis of extensive ulcerative colitis, inflammatory polyps were detected. Three patients were on treatment with mesalazine, one with azathioprine and other with infliximab. All of them were asymptomatic and the endoscopy did not show macroscopic activity (endoscopic Mayo score=0) or histological activity. The median values of calprotectin were 422µg/g (IQR: 298-2,408) and they remained elevated in a second measurement. In 4 of the patients the inflammatory polyps were multiple and small in size. The other patient had a polyp measuring 4cm. DISCUSSION: In clinical practice we can find high faecal calprotectin levels not due to the presence of ulcerative colitis activity, but due to other lesions such as inflammatory polyps. This fact must be taken into account before carrying out relevant changes such as step-up therapy to immunosuppressive drugs or biological drugs in patients with confirmed high calprotectin levels.

Randomized clinical trial evaluating the effect of a visual educational leaflet on the preparation of colonoscopies in hospitalized patients

Background: the safety and diagnostic accuracy of colonoscopies depends on the quality of colon cleansing. Several factors have been reported that affect the quality of bowel cleansing, hospitalization being one of them. Aims: the aim of the study was to investigate whether a visual educational leaflet improved the level of cleanliness achieved in hospitalized patients undergoing a colonoscopy and to identify predictors of a poor bowel preparation. Methods: a prospective, single-center, endoscopist-blinded, randomized controlled trial was performed. The intervention group was given a visual educational leaflet and both groups received four liters of polyethylene glycol solution. Demographic data, personal history, reason for admission and indication for colonoscopy, work shift during which the procedure was performed and endoscopy findings were collected. The Boston Bowel Preparation Scale (BBPS) was used to assess the bowel preparation. Results: one hundred and thirty-six patients were included in the study; 51.5% were male, with a mean age of 64.3 +/- 17.6 years. The educational leaflet did not result in a difference in the total BBPS obtained between the standard group and the intervention group (7 [6-9] vs 6 [5.7-9]; p = 0.17). According to the multivariable analysis, the only factors associated with a poor bowel cleansing were heart disease (OR 3.37 [1.34-8.46]; p = 0.010) and colorectal cancer (OR 3.82 [1.26-11.61]; p = 0.018). Conclusion: the use of a visual educational leaflet for the preparation of colonoscopies did not provide a significant improvement in hospitalized patients in our health area. Heart disease was identified as the only predictor of poor preparation for colonoscopy

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Randomized clinical trial evaluating the effect of a visual educational leaflet on the preparation of colonoscopies in hospitalized patients.

BACKGROUND: the safety and diagnostic accuracy of colonoscopies depends on the quality of colon cleansing. Several factors have been reported that affect the quality of bowel cleansing, hospitalization being one of them. AIMS: the aim of the study was to investigate whether a visual educational leaflet improved the level of cleanliness achieved in hospitalized patients undergoing a colonoscopy and to identify predictors of a poor bowel preparation. METHODS: a prospective, single-center, endoscopist-blinded, randomized controlled trial was performed. The intervention group was given a visual educational leaflet and both groups received four liters of polyethylene glycol solution. Demographic data, personal history, reason for admission and indication for colonoscopy, work shift during which the procedure was performed and endoscopy findings were collected. The Boston Bowel Preparation Scale (BBPS) was used to assess the bowel preparation. RESULTS: one hundred and thirty-six patients were included in the study; 51.5% were male, with a mean age of 64.3 ± 17.6 years. The educational leaflet did not result in a difference in the total BBPS obtained between the standard group and the intervention group (7 [6-9] vs 6 [5.7-9]; p = 0.17). According to the multivariable analysis, the only factors associated with a poor bowel cleansing were heart disease (OR 3.37 [1.34-8.46]; p = 0.010) and colorectal cancer (OR 3.82 [1.26-11.61]; p = 0.018). CONCLUSION: the use of a visual educational leaflet for the preparation of colonoscopies did not provide a significant improvement in hospitalized patients in our health area. Heart disease was identified as the only predictor of poor preparation for colonoscopy.

Self-Formation Assessed by Cumulative Summation Test Does Not Reach Recommended Thresholds for Optical Diagnosis of Colorectal Polyps ≤ 7 mm.

BACKGROUND AND AIMS: Accurate optical diagnosis of diminutive polyps would allow implementing a resect and discard strategy. We evaluated the learning curve of a single training session followed by self-education in subjects with no endoscopic experience. METHODS: Learning curves were evaluated in 38 subjects employing learning curve-cumulative summation (LC-CUSUM) tests, with each participant attending one training session regarding narrow band imaging and optical diagnosis and then individually assessing 100 lesions, receiving feedback after each diagnosis. Diagnostic accuracy was subsequently evaluated in 180 patients with lesions ≤ 7 mm. Evaluators predicted each polyp's histology and recommended a surveillance interval. Determinants of accuracy were explored using regression analysis. RESULTS: According to the LC-CUSUM curve, 20 evaluators (52.6%) reached diagnostic competence after 57 lesions (IQR 55-76.5). During the diagnostic performance assessment, 11,666 diagnoses and 6840 follow-up recommendations were generated. Considering high confidence diagnoses, accuracy was 81.3% (80.5-82.1%), negative predictive value (NPV) for rectosigmoid adenomas 78.6% (76.4-80.6%), and sensitivity for adenomas 86.6% (85.8-87.4%). Two (5.3%) evaluators reached a ≥ 90% accuracy, 3 (7.9%) presented a NPV for rectosigmoid adenomas ≥ 90%, and 18 (47.4%) a sensitivity for adenomas ≥ 90%. Multivariable logistic regression showed high confidence and size ≥ 5 mm as the strongest predictors of accuracy. Fifteen (39.5%) evaluators recommended a correct or reduced follow-up interval in over 90% of subjects. CONCLUSIONS: Self-formation after a single training session did not allow most evaluators to reach the required accuracy. LC-CUSUM tests did not identify competent evaluators. Despite these results, 86.7% of follow-up intervals would have been corrected or reduced.

Infección crónica por virus de la hepatitis B antígeno e negativo. Manejo en función de puntos de corte de glutámico-pirúvica transaminasa y ácido desoxirribonucleico del virus de la hepatitis B / Hepatitis B virus e antigen-negative chronic infection. Treatment based on glutamic pyruvic transaminase and hepatitis B virus deoxyribonucleic acid cut-off values

Objetivos: Buscar puntos de corte de la glutámico-pirúvica transaminasa (GPT) y de ADN del virus de hepatitis B (ADN-VHB) al diagnóstico, en pacientes con infección crónica VHB antígeno e negativo (AgHBe(-)), que puedan ser predictores de la evolución, pronóstico y/o de la necesidad de terapia antiviral. Métodos: Estudio observacional de cohortes retrospectivo de pacientes diagnosticados de infección crónica por VHB AgHBe(-) (2005-2012). Se investigó un punto de corte de GPT normal al diagnóstico que predijera la alteración de esta en la evolución, de ADN-VHB basal que predijera la elevación de este por encima de 2.000UI/ml, y de GPT y ADN-VHB como predictores de la necesidad de tratamiento, mediante curvas ROC. Resultados: Se incluyeron 126 pacientes (seguimiento: 42,1±21,5meses), de los cuales 93 tenían GPT normal al diagnóstico. En el análisis de curvas ROC el punto de corte de ADN-VHB que mejor predijo la elevación de este por encima de 2.000UI/ml fue 900UI/ml (sensibilidad: 90%; especificidad: 88%; VPP: 79%; VPN: 100%; precisión diagnóstica: 89%), y el que mejor predijo la alteración de GPT normal al diagnóstico posteriormente elevada fue 25mU/ml (sensibilidad: 95,4%; especificidad: 81,6%; VPP: 67%; VPN: 96%; precisión diagnóstica: 80,6%). Los pacientes con GPT 26-40mU/ml al diagnóstico presentaron más complicaciones o necesidad de tratamiento que aquellos con GPT≤25mU/ml (p<0,05). La combinación de GPT y ADN-VHB que maximizó la necesidad de tratamiento fue 38mU/ml de GPT y 6.000UI/ml de ADN-VHB (sensibilidad: 75%; especificidad: 93,4%; VVP: 60%; VPN: 96,6%). Conclusión: Los pacientes VHB AgHBe(-) con GPT<25mU/ml y ADN-VHB<9.000UI/ml al diagnóstico presentan buena evolución y podrían no requerir un seguimiento tan estrecho en los primeros años desde el diagnóstico (AU)

Objectives: To identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(-)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. Methods: A retrospective and observational cohort study of patients diagnosed with HBeAg(-) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. Results: 126 patients were enrolled (follow-up: 42.1±21.5months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT≤25mU/ml (P<.05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38mU/ml of GPT and 6,000IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). Conclusion: HBeAg(-) patients with GPT<25mU/ml and HBV-DNA<900IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosis (AU)

Hepatitis B virus e antigen-negative chronic infection. Treatment based on glutamic pyruvic transaminase and hepatitis B virus deoxyribonucleic acid cut-off values. / Infección crónica por virus de la hepatitis B antígeno e negativo. Manejo en función de puntos de corte de glutámico-pirúvica transaminasa y ácido desoxirribonucleico del virus de la hepatitis B.

OBJECTIVES: To identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(-)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. METHODS: A retrospective and observational cohort study of patients diagnosed with HBeAg(-) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. RESULTS: 126 patients were enrolled (follow-up: 42.1±21.5months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT≤25mU/ml (P<.05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38mU/ml of GPT and 6,000IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). CONCLUSION: HBeAg(-) patients with GPT<25mU/ml and HBV-DNA<900IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosis.

Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo / Characteristics and course of chronic hepatitis B e antigen-negative infection

OBJETIVO: Describir las características epidemiológicas, analíticas, histológicas y evolutivas de pacientes con infección crónica por VHB AgHBe-negativo. MATERIAL Y MÉTODOS: Estudio observacional de cohorte retrospectivo de pacientes diagnosticados de infección crónica VHB AgHBe-negativo (2005-2012) sin otras hepatopatías. RESULTADOS: Se incluyeron 138 pacientes con edad media de 40,5 ± 12,2 años, de los cuales el 54% eran mujeres. El 38% eran extranjeros, con incremento de estos en los últimos años (p < 0,001). Las transaminasas en el momento del diagnóstico eran normales en casi el 75% y el ADN-VHB < 2.000 UI/ml en el 56%. En los portadores inactivos existe una disminución progresiva de los niveles de ADN-VHB en el periodo de estudio. En el 47% se evaluó la fibrosis hepática por Fibroscan ® o biopsia hepática: el 55,4% resultó normal y el 6,1% reportó cirrosis. El 77,77% eran portadores inactivos. Precisaron tratamiento el 15,5% (20% por cirrosis y 80% por HBC AgHBe-negativo). Aclararon el AgHBs 5 pacientes (tasa anual 0,94%), presentando todos al diagnóstico ADN-VHB < 2.000 UI/ml. Cinco pacientes desarrollaron alguna complicación (3,6%), 4 de ellos carcinoma hepatocelular (CHC) (solo 2 presentaban cirrosis). Hubo un fallecimiento relacionado con el VHB (0,72%). CONCLUSIÓN: Entre los enfermos con infección crónica por VHB AgHBe-negativo predominan los portadores inactivos. Se produce un progresivo descenso de ADN-VHB en los primeros años tras el diagnóstico. Desarrollan poca morbimortalidad, especialmente si existe GPT normal y ADN-VHB bajo al diagnóstico. Un número no despreciable de pacientes precisa tratamiento. El CHC es la complicación más frecuente, incluso en pacientes sin cirrosis

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5 ± 12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P < .001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was < 2,000 IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan ® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis

Characteristics and course of chronic hepatitis B e antigen-negative infection. / Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo.

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5±12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P<.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was <2,000IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis.

Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes / Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients

Objetivo El objetivo de nuestro estudio fue conocer las características clínicas, analíticas, serológicas e histológicas de los portadores crónicos del virus de la hepatitis B en nuestra área. Material y métodos Se realizó un estudio de cohortes retrospectivo que incluyó pacientes mayores de 13 años portadores crónicos del AgHBs, valorados en nuestro servicio desde enero de 2000.ResultadosSe incluyeron 474 enfermos. Al diagnóstico el 55,49% fueron varones, con una edad media de 41,05±13,93 y GPT normal en el 57,17% de los casos, siendo el 87,76% AgHBe(−). Las coinfecciones VHC y VHD ocurrieron en el 3,62 y 1,86%, respectivamente. Se realizó biopsia hepática al 31,22%, presentando el 63,51% grados variables de inflamación-fibrosis, y el 12,84%, cirrosis. Los pacientes AgHBe(+) en comparación con los (−) fueron más jóvenes y presentaron mayor actividad de la enfermedad de forma estadísticamente significativa. Los pacientes en fase inmunotolerante fueron los más infrecuentes (5,26%), y los que presentaban HBC AgHBe(−) los (..) (AU)

Objective To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. Material and methods A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000.ResultsA total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(−). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(−) patients, those who were AgHBe(+) were younger and had greater disease activity. This (..) (AU)

[Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients]. / Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes.

OBJECTIVE: To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. MATERIAL AND METHODS: A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000. RESULTS: A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(-). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(-) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(-) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%. CONCLUSION: Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(-), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.

Amyloidosis and Crohn´s disease.

Secondary amyloidosis is a rare but serious complication of inflammatory bowel disease that may influence the prognosis even more than the underlying disease. Due to a better knowledge of the association of secondary amyloidosis to inflammatory bowel disease, early diagnosis of this complication is becoming more frequent, but its treatment continues to pose a challenge. We report 4 cases of patients with Crohn´s disease and amyloidosis diagnosed in the inflammatory bowel disease Units of Toledo and Ciudad Real, which represent 0.68% of the patients with Crohn´s disease of our health areas. There have been not cases of amyloidosis in patients with ulcerative colitis. In our 4 patients the secondary amyloidosis was clearly related to Crohn´s disease,which was often of fistulising type. The predominant clinical picture of amyloidosis was nephrotic syndrome. The patients responded to medical and surgical treatment of Crohn´s disease and colchicine, which improved renal function in all cases except in one who required kidney transplantation.