Differences in the incidence and clinical evolution of early neurotoxicity after liver transplantation based on tacrolimus formulation used in the immunosuppressive induction protocol.

INTRODUCTION: Posttransplant early calcineurin inhibitor (CNI)-induced neurotoxicity (ECIIN) was related to high CNI levels, among other factors. Minimizing exposure could modify its incidence or clinical evolution. OBJECTIVE: To compare the incidence, predisposing factors, and clinical evolution of ECIIN after immunosuppressive induction with low-dose tacrolimus-MR (Advagraf) or conventional dose tacrolimus (Prograf). PATIENTS AND METHODS: We matched 71 patients treated with an immunosuppression induction schedule with basiliximab and low doses of Advagraf (cases group) 1:1 by recipient age and indication for liver transplantation (OLT) with patients treated with a conventional tacrolimus regimen (control group). Baseline characteristics, liver and kidney function, operative technical characteristics, kidney function, and C0 tacrolimus levels at several time points after liver OLT were analyzed. RESULTS: There were 31 cases of ECIIN (21%), 14 in the cases group (20%) and 17 in the control group (24%; P < .001). The incidence of ECIIN was higher in alcoholic liver disease (odds ratio [OR], 8.2; 95% CI, 2.3-28.6; P < .001) and past history of encephalopathy (OR, 2.6; 95% CI, 1.16-5.9; P < .02). Among cases, the incidence of ECIIN was higher when encephalopathy signs were present at time of transplantation (36% vs 12%; P < .001). Control of ECIIN required a switch to cyclosporine therapy in all those in the cases group, whereas this was only needed for 9 cases in the control group (47%; P < .001). CONCLUSION: In this study, although the incidence rate of neurotoxicity induced by Advagraf was lower than the induced by Prograf, it did not respond to routine treatment and required a significantly higher rate of switch to cyclosporine for its control.

Viral and host factors related with histopathologic activity in patients with chronic hepatitis B and moderate or intermittently elevated alanine aminotransferase levels.

OBJECTIVE: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. PATIENTS AND METHODS: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 10³ IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥2 or fibrosis ≥2 according to Scheuer Classification. RESULTS: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNA-HBV > 2 x 10³ IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). CONCLUSION: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases.

Influencia de factores virales y del huésped en la actividad histológica en pacientes con hepatitis crónica por virus de la hepatitis B y elevación moderada o intermitente de alanina aminotransferasa / No disponible

Objetivo: analizar factores virales y del huésped relacionados con actividad histológica en un subgrupo de pacientes con hepatitis crónica B y elevación intermitente o moderada de alanina aminotransferasa (ALT), y el umbral que determine daño histológico indicativo de tratamiento. Pacientes y métodos: análisis retrospectivo de parámetros virales y del huésped en 89 pacientes con hepatitis crónica B biopsiados consecutivamente por elevación intermitente o moderada de ALT [1-2 x USN (USN = 39 UI/ml)]. Fueron analizados edad, sexo, ALT, HBeAg, carga viral y genotipo. Se consideró como lesion histológica avanzada un Índice de Knodell (IK) > 7, e indicativa de tratamiento la inflamación lobulillar ≥ 2 o fibrosis ≥ 2 según la clasificación de Scheuer. Resultados: existió un IK > 7 y lesión indicativa de tratamiento en 47,8 y 60,7%, respectivamente. La edad, sexo varón, ALT y carga viral se relacionaron con lesión avanzada (p < 0,05). La frecuencia de lesión indicativa de tratamiento fue mayor en pacientes con ALT > USN (69,1 vs. 47,1%, p = 0,04). La frecuencia de lesión avanzada no fue significativamente mayor cuando se consideraron como puntos de corte la edad de 40 años o ADNVHB > 2 x 103 UI/ml o positividad de HBeAg. Se observó menor actividad histológica en pacientes con genotipo D respecto a aquellos infectados con otros genotipos (p < 0,05). Conclusión: una mayor frecuencia de lesión avanzada en pacientes con hepatitis crónica B y elevación intermitente o moderada de ALT hacen recomendable la biopsia hepática independientemente de la carga viral y positividad de HBeAg. Factores como la edad, sexo o genotipo pueden ayudar de forma individual a dicha indicación(AU)

Objective: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. Patients and methods: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 103 IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥ 2 or fibrosis ≥ 2 according to Scheuer Classification. Results: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNAHBV > 2 x 103 IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). Conclusion: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases(AU)

Valganciclovir-induced leukopenia in liver transplant recipients: influence of concomitant use of mycophenolate mofetil.

INTRODUCTION: An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported. OBJECTIVE: To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors. PATIENTS AND METHODS: Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections. RESULTS: Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed. CONCLUSIONS: In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.

Miocarditis por clozapina / Clozapine of myocarditis

No disponible

No disponible

[Late-onset Wilsons disease]. / Enfermedad de Wilson de manifestación tardía.

A 58-year old male with a past history of psychiatric disorders was studied for a persistent serum transaminase increase. Low serum ceruloplasmin level (lower than 3 mg/dL), increased urinary copper excretion, and increased liver tissue copper concentration (1050 mcg/g dry weight) confirmed the diagnosis of Wilsons disease. Slit lamp examination did not show Kayser-Fleischer rings. D-penicilamin therapy was followed by serum transaminase normalization. Similar late-onset cases of Wilsons disease are exceptional, but confirm the clinical heterogeneity of the disease.

Enfermedad de Wilson de manifestación tardía / Late-onset Wilson's disease

Un varón de 58 años con antecedente de trastornos psiquiátricos fue estudiado por elevación persistente de transaminasas. Se estableció el diagnóstico de enfermedad de Wilson en base a una ceruloplasmina sérica baja (menor de 3 mg/dL), una excreción urinaria de cobre aumentada y una concentración hepática de cobre aumentada (1050 mcg por gramo de tejido seco). No se observó anillo de Kayser-Fleischer en el estudio con lámpara de hendidura. Fue tratado con D-penicilamina, con normalización progresiva de las transaminasas. Los casos similares de enfermedad de Wilson de manifestación tardía son excepcionales, pero confirman la heterogeneidad clínica de la enfermedad. (AU)

[Complications and yield of percutaneous liver biopsy with ultrasonographic marking]. / Complicaciones y rendimiento de la biopsia hepática percutánea con marcado ecográfico.

OBJECTIVES: To describe the complications and the diagnostic yield of percutaneous liver biopsies performed under ultrasonographic control in an Internal Medicine department. PATIENTS AND METHODS: A total of 750 percutaneous liver biopsies were performed at the Internal Medicine department of our institution during the 1995-2001 time period. The Menghini technique was employed previous ultrasonographic marking of the puncture site was performed by the same physicians who performed the biopsy. Major and minor complications as well as the diagnostic yield (obtention of diagnostic hepatic tissue) of the technique were recorded. RESULTS: No deaths occurred in our series. Two patients (0.3%) had major complications presenting as liver subcapsular hematoma with hemoperitoneum which resolved with conservative measures. One of them was a male patient with acute leukemia and the other was a woman on antiaggregant therapy. Eight patients (1.1%) had minor complications (vasovagal syncope), all of them young males. In three cases no adequate material for diagnosis was obtained (technique yield 99.6%). CONCLUSIONS: In our series, percutaneous liver biopsy with ultrasonographic marking is a diagnostic technique associated with a low rate of severe complications and with a high diagnostic yield. The use of ultrasonographic marking by the same physicians performed the biopsy does not involve a longer time or increased cost of the technique, provides more safety in the procedure and has a low morbidity rate. This procedure could be used on a routine basis for all percutaneous liver biopsies.

Complicaciones y rendimiento de la biopsia hepáticapercutánea con marcado ecográfico / Complications and diagnostic yield of percutaneous liver biopsy with ultrasonographic marking

Objetivos. Describir las complicaciones y el rendimiento diagnóstico de las biopsias hepáticas percutáneas realizadas con control ecográfico en un servicio de Medicina Interna. Pacientes y métodos. Se analizaron las 750 biopsias hepáticas percutáneas realizadas en un servicio de Medicina Interna durante el período 1995-2001. Se utilizó la técnica de Menghini con marcado ecográfico previo del lugar de punción efectuado por los mismos facultativos que realizaron la biopsia. Se recogieron las complicaciones mayores y menores habidas y el rendimiento de la prueba (obtención o no de tejido hepático diagnóstico).Resultados. No hubo mortalidad en nuestra serie. Dos pacientes (0,3 por ciento) presentaron complicaciones mayores en forma de hematoma subcapsular hepático con hemoperitoneo, que se resolvieron con medidas conservadoras. Uno de ellos era un varón con leucemia aguda y el otro una mujer antiagregada. Presentaron complicaciones menores (síncope vagal) 8 pacientes (1,1 por ciento), todos ellos varones jóvenes. En 3 casos no se obtuvo material suficiente para el diagnóstico (rendimiento de la prueba 99,6 por ciento).Conclusiones. En nuestra experiencia, la biopsia hepática percutánea con marcado ecográfico es una prueba diagnóstica con una baja tasa de complicaciones graves y un elevado rendimiento. El empleo de la ecografía por los mismos facultativos que realizan la biopsia no supone un incremento del tiempo o del coste económico de la técnica, aporta más seguridad en el procedimiento y una baja morbilidad. Este procedimiento podría ser rutinario en todas las biopsias hepáticas percutáneas (AU)

Mutaciones en el gen HFE (C282Y, H63D, S65C) en pacientes alcohólicos con datos de sobrecarga de hierro / Mutations in the HFE gene (C282Y, H63D, S65C) in alcoholic patients with finding of iron overload

Introducción. La patogenia de la sobrecarga de hierro en alcohólicos no está enteramente aclarada. La frecuencia de las mutaciones del gen de la hemocromatosis hereditaria (HFE) es alta en la población. Los heterocigotos presentan datos de sobrecarga de hierro similares a los de los alcohólicos. Objetivo. Analizar si el exceso de hierro en alcohólicos se asocia a las mutaciones C282Y, H63D o S65C del gen HFE. Pacientes y métodos. Se estudiaron 32 alcohólicos activos (29 varones y tres mujeres, de edades entre 30-67 años) que presentaban datos de sobrecarga de hierro (ferritinemia elevada con o sin saturación de transferrina aumentada). En todos se estudiaron las mutaciones C282Y, H63D y S65C. En 16 casos se dispuso de histología hepática. Se compararon los datos de sobrecarga de hierro en los pacientes con y sin mutaciones. Resultados. Veintidós pacientes (68,8 por ciento) no presentaban ninguna mutación, uno (3,1 por ciento) era heterocigoto-C282Y, tres (9,4 por ciento) eran homocigotosH63D, 4 (12,5 por ciento) eran heterocigotos-H63D y dos pacientes (6,3 por ciento) eran heterocigotos compuestos (C282Y/H63D). Ningún paciente era homocigotoC282Y ni presentó la mutación S65C. La saturación de transferrina, la ferritinemia y el índice de hierro hepático fueron similares en los pacientes con y sin alguna mutación. Tres pacientes (9,3 por ciento) fueron etiquetados de hemocromatosis. Uno era homocigoto-H63D, otro heterocigoto compuesto (C282Y/H63D) y en la restante no se encontró ninguna de las mutaciones. Conclusión. En nuestro medio la sobrecarga de hierro en alcohólicos parece independiente de la presencia de las mutaciones C282Y, H63D y S65C en el gen HFE (AU)

Papel del internista general en los trasplantes de órganos. Situación actual en España / Role of general internists in adult organ transplantation in Spain

Antecedentes: No existen datos acerca de la participación de los Internistas Generales en los trasplantes de órgano en España. Objetivo: Conocer la situación actual de la participación de los Internistas Generales y los Servicios de Medicina Interna General en los programas de trasplante en España. Materiales y métodos: Se envió una encuesta con tres preguntas concretas de elección múltiple a los responsables del área médica de los 67 grupos de trasplante de órgano (riñón, hígado, corazón y pulmón) de España. Contestaron a la encuesta un total de 43 equipos (64 %). Resultados: Sólo en 8 grupos de trasplante (18 %) existen Internistas Generales dentro del equipo habitual, un hecho además casi restringido al trasplante hepático. Un total de 18 equipos (42 %) nunca solicitan la colaboración de Medicina Interna. A la hora de las consultas a otros servicios, ningún equipo de trasplante prefiere dirigirlas a Medicina Interna respecto a otras Especialidades. El problema concreto de las Enfermedades Infecciosas es llevado por el propio equipo de trasplante o se consulta con Unidades específicas, pero nunca se consulta con Servicios de Medicina Interna General. Conclusiones: La participación de los Internistas Generales en los trasplantes de órganos de adultos en España es escasa, salvo en el caso del trasplante hepático. Las consultas a los Internistas Generales por parte de los equipos de trasplante son también escasas, salvo que los Internistas estén integrados en Unidades de Enfermedades Infecciosas (AU)

[Plasmacytoma of the thyroid. A review apropos a case]. / Plasmacitoma de la glándula tiroides. Revisión a propósito de un caso.

Isolated presentation of outer bone marrow plasmatic cell neoplasia are non-frequent (less than 10% of all plasmacytomas). Thyroid gland involvement is rarely described. A case where immunohistochemistry confirmed the monoclonal type of proliferative cell is presented. Clinical, pathological and diagnosis criteria, as well as response to treatment, are reviewed.

[Clinical characteristics and prognostic criteria in alcoholic hepatitis and alcoholic hepatitis with cirrhosis]. / Características clínicas y criterios pronósticos en la hepatitis alcohólica y hepatitis alcohólica con cirrosis.

A comparative study of clinical and biological features and of the immediate prognosis was made in 46 patients with alcoholic hepatitis and 19 patients with alcoholic hepatitis with liver cirrhosis. The presence of cirrhosis has different clinical manifestations and a more intense alteration of albumin, prothrombin, total bilirubin and immunoglobulins (p less than 0.01). The development of ascites, encephalopathy and hepatorenal syndrome (p less than 0.05) and albumin, prothrombin and total bilirubin values at admission (p less than 0.01) were the best parameters to identify the patients with a poorer prognosis. There were no significant differences between both groups in mortality, frequency of encephalopathy or renal failure.

[Duodenocolonic fistula caused by carcinoma of the cecum]. / Fístula duodenocólica por carcinoma del ciego.

Duodenocolonic fistulas of malignant origin are an uncommon finding. The point of origin of the fistula is almost always cancer of the hepatic angle of the colon. We report a patient with this rare entity which originated from a cecal carcinoma, and interpret it as an anatomic variant of the subhepatic position. The cases published are reviewed and the difficulties of reaching a therapeutic decision once the diagnosis is established are highlighted.

[Recurrent Budd-Chiari syndrome as a complication of nocturnal paroxysmal hemoglobinuria]. / Síndrome de Budd-Chiari recidivante como complicación de una hemoglobinuria paroxística nocturna.

Budd-Chiari syndrome is a frequent complication of nocturnal paroxysmal hemoglobinuria, histologic and angiographic study being fundamental for diagnosis. We emphasize the importance of ultrasonography and abdominal CAT as noninvasive methods of early diagnosis, and the value of ultrasonography in the follow-up of these patients. Radical therapy of the disease from onset is a determinant of the final prognosis of these patients, as well as early treatment of thrombosis with thrombolytics and/or anticoagulants.