Hepatotoxicity associated with statin use: analysis of the cases included in the Spanish Hepatotoxicity Registry.

OBJECTIVES: The hepatotoxic potential of statins is controversial. The objectives of this study were to describe the relative frequency of hepatotoxicity caused by statins and the phenotypes found in Spain. PATIENTS AND METHODS: The incidence of hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH) were studied and compared with those attributed to other drugs. RESULTS: Between April 1994 and August 2012, the REH included a total of 858 cases of which 47 (5.5 %) were attributed to statins. Of these, 16 were due to atorvastatin (34 %); 13 to simvastatin (27.7 %); 12 to fluvastatin (25.5 %); 4 to lovastatin (8.5 %) and 2 to pravastatin (4.3 %). Statins represented approximately half of the cardiovascular group which occupied 3rd place (10 %), after anti-infectious agents (37 %) and central nervous system drugs (14 %). The hepatocellular pattern was predominant, especially in the simvastatin group (85%), the cholestatic/mixed pattern was more frequent with fluvastatin (66 %) and had a similar distribution to atorvastatin. Patients with statin-induced toxicity were older (62 years versus 53 years, p < 0.001) and more often demonstrated anautoimmune hepatitis phenotype (8.5 % versus 1.4 %, p < 0.003). CONCLUSIONS: Statins are not a common cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the greatest number of incidents. The liver injury pattern varies among the different statins. The hepatitis phenotype with autoimmune features appears to be a characteristic signature of statin-induced hepatotoxicity.

Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis.

BACKGROUND & AIMS: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. METHODS: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. RESULTS: Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. CONCLUSIONS: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

Hepatotoxicidad asociada a sertralina / No disponible

No disponible

Double-balloon enteroscopy: a descriptive study of 50 explorations.

AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

A shortened, 2-hour rifampin test: a useful tool in Gilbert's syndrome.

INTRODUCTION: Diagnosis of Gilbert's disease often involves unnecessary testing and patient anxiety. Rifampin test can support the diagnosis; it has been described in short series and lacks standardization in dose, collection times, result presentation and interpretation. Our objective was to compare the response to oral rifampin in a series of patients with Gilbert's disease, 2 and 4 h after drug administration. PATIENTS AND METHODS: Eighty-nine patients with Gilbert's disease (elevated total bilirubin with no hepatopathy or hemolysis) were recruited. After a basal blood collection, 900 mg rifampin were administered per os and new samples were drawn 2 and 4 h later. Total and esterified bilirubin were measured in every sample. Haptoglobin concentration was also analyzed. RESULTS: When expressed as relative increase with respect to basal values, variations observed 2 h after rifampin intake were all above 15%. A significant correlation (r = 0.902; p = 0.000) was found between relative increases 2 and 4 h after drug administration. No significant variations were found in haptoglobin concentrations. CONCLUSION: Rifampin test is useful in diagnosing Gilbert's disease, but variations in total bilirubin concentrations (basal and post-rifampin) make that no absolute cut-off value can be used. Correlation between 2- and 4-h relative increases suggests that a shortened version could simplify the test.

Enteroscopia de doble balón: estudio descriptivo de 50 exploraciones / Double-balloon enteroscopy: a descriptive study of 50 explorations

Objetivo: valorar la utilidad de la enteroscopia de doble balón en enfermedades de intestino delgado. Diseño: estudio prospectivo descriptivo de 50 enteroscopias consecutivas (diciembre 2004 a julio 2005), analizando diagnóstico y terapéutica. Pacientes: cuarenta y cuatro pacientes (33 con cápsula endoscópica previa) con hemorragia digestiva oculta o lesiones detectadas mediante cápsula (angiodisplasias, pólipos, úlceras, enfermedad de Crohn, celiaca refractaria y tumores). Resultados: se realizó enteroscopia vía oral a 44 pacientes y vía oral más anal a 6. Por vía oral se progresó hasta íleon en todos los casos excepto uno (estenosis yeyunal), por vía anal en 4 de 7 (3 casos con dificultad de paso por Bahuin). La duración media fue 73 minutos. Se detectaron angiodisplasias (19 casos), úlceras en enteropatía por AINE, enfermedad de Crohn, enfermedad de Waldenström, y divertículos. Se realizaron biopsias en yeyuno-íleon en un tercio de los casos (adenocarcinoma, linfangiectasias secundarias a tumor sobre celíaca, enfermedad de Whipple). Se realizó terapéutica con argón a 19 pacientes con angiodisplasias (1 a 20 lesiones), polipectomía a 4 pacientes con pólipos esporádicos o Peutz Jeghers (1 a 15 pólipos) y se extrajo una cápsula endoscópica retenida en una estenosis. Conclusiones: la enteroscopia de doble balón es una técnica útil y eficaz en el diagnóstico y tratamiento de las lesiones del intestino delgado, complementando a la cápsula endoscópica. Hacen falta más estudios para analizar el impacto esperado en el cambio del manejo de estos pacientes

Aim: to evaluate the utility of double-balloon enteroscopy for small-bowel disease. Design: a prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. Patients: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn´s disease, tumors, and refractory celiac disease. Results: we carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn’s disease, diverticulosis, and Waldenström’s disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple’s disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. Conclusions: double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition

Prueba breve (2 horas) con rifampicina: una herramienta útil en el síndrome de Gilbert / A shortened, 2-hour rifampin test: a useful tool in Gilbert's syndrome

OBJETIVO. Comparar la respuesta a las 2 y a las 4 horas de la administración oral de rifampicina en una serie de pacientes con enfermedad de Gilbert. INTRODUCCIÓN. El diagnóstico de la enfermedad de Gilbert conlleva, a menudo, la realización de pruebas innecesarias que incrementan la ansiedad del paciente. La prueba de la rifampicina puede apoyar el diagnóstico. Esta prueba ha sido descrita en grupos pequeños de pacientes y todavía carece de estandarización en lo relativo a la dosis, los momentos de obtención de las muestras de sangre, la presentación del resultado y su interpretación. PACIENTES Y MÉTODOS. En el estudio participaron 89 pacientes con enfermedad de Gilbert (incremento de la concentración de bilirrubina total sin hepatopatía ni hemólisis). Tras la obtención de una muestra inicial de sangre, se administraron 900 mg de rifampicina por vía oral y, posteriormente, a las 2 y a las 4 horas de esta administración, se volvieron a obtener muestras de sangre. En cada muestra se determinaron las concentraciones de bilirrubina total y de bilirrubina esterificada. También se determinó la concentración de haptoglobina. RESULTADOS. Mediante su expresión como el incremento relativo respecto a los valores basales, todas las variaciones observadas a las 2 horas de la administración de rifampicina fueron superiores al 15%. Se observó una correlación significativa (r = 0,902; p = 0,000) entre los incrementos relativos detectados a las 2 y a las 4 horas de la administración del medicamento. No se detectaron variaciones significativas en las concentraciones de haptoglobina. CONCLUSIÓN. La prueba de la rifampicina es útil para establecer el diagnóstico de la enfermedad de Gilbert, pero las variaciones en las concentraciones de bilirrubina total (basal y tras la administración de rifampicina) no permiten establecer un valor umbral absoluto. La correlación observada entre los incrementos relativos a las 2 y a las 4 horas indica que la versión breve de la prueba (2 horas) podría simplificar su aplicación

Introduction: Diagnosis of Gilbert's disease often involves unnecessary testing and patient anxiety. Rifampin test can support the diagnosis; it has been described in short series and lacks standardization in dose, collection times, result presentation and interpretation. Our objective was to compare the response to oral rifampin in a series of patients with Gilbert's disease, 2 and 4 h after drug administration. Patients and methods: Eighty-nine patients with Gilbert's disease (elevated total bilirubin with no hepatopathy or hemolysis) were recruited. After a basal blood collection, 900 mg rifampin were administered per os and new samples were drawn 2 and 4 h later. Total and esterified bilirubin were measured in every sample. Haptoglobin concentration was also analyzed. Results: When expressed as relative increase with respect to basal values, variations observed 2 h after rifampin intake were all above 15%. A significant correlation (r = 0.902; p = 0.000) was found between relative increases 2 and 4 h after drug administration. No significant variations were found in haptoglobin concentrations. Conclusion: Rifampin test is useful in diagnosing Gilbert's disease, but variations in total bilirubin concentrations (basal and post-rifampin) make that no absolute cut-off value can be used. Correlation between 2- and 4-h relative increases suggests that a shortened version could simplify the test

[Gastrointestinal alterations in a female patient with common variable immunodeficiency]. / Alteraciones gastrointestinales en una paciente con inmunodeficiencia variable común.

We present the case of a 33-year-old woman who complained of intermittent diarrhea over the previous 8 years and who was diagnosed with common variable immunodeficiency. The woman presented antral atrophic gastritis, partial atrophy of the duodenal villi, nodular lymphoid hyperplasia of the small intestine and lymphocytic colitis. We also review the literature.

[Cerebral venous sinus thrombosis and ulcerative colitis]. / Trombosis de senos venosos cerebrales y colitis ulcerosa.

Hypercoagulability is a extraintestinal manifestation of inflammatory bowel disease, which could provoke thromboembolic phenomena. Central nervous system venous thrombosis is a rare complication and could be unnoticed. We report on a patient with ulcerative colitis who presented cerebral venous sinus thrombosis as the first manifestation of a hypercoagulable state. We review the literature and discuss about the pathogenic mechanisms of such complication.

Trombosis de senos venosos cerebrales y colitis ulcerosa / Cerebral venous sinus thrombosis and ulcerative colitis

La EEI se acompaña de múltiples manifestaciones extraintestinales, entre ellas un estado de hipercoagulabilidad que puede dar lugar a fenómenos tromboembólicos. Entre estos últimos están las trombosis venosas cerebrales (TVC) que son raras y pueden dar lugar a un cuadro poco llamativo, pasando desapercibidas. Describimos el caso de un paciente diagnosticado previamente de colitis ulcerosa que presentó TVC como primera manifestación de un síndrome de hipercoagulabilidad. Se revisa la literatura y se comentan los mecanismos patogénicos (AU)