espanolIntroduccion. Evaluar el perfil clinico y el manejo de los pacientes con infeccion por hepatitis C cronica (VHC) en un estudio observacional en hospitales espanoles. Metodos. El estudio incluye una fase inicial de registro transversal de datos agregados (primera fase del estudio) en la cual investigadores de 48 hospitales en 14 regiones diferentes de Espana recopilaron datos de aproximadamente 20 pacientes atendidos consecutivamente en consulta (un total de 1.000 pacientes) en los que se analizo, en cada uno de ellos, las caracteristicas generales de la infeccion por VHC de cualquier genotipo. Durante la segunda fase del estudio se realizo una evaluacion retrospectiva de datos procedentes de 878 pacientes exclusivamente portadores del genotipo 1 del VHC. Se establecieron ocho perfiles clinicos predefinidos con el objetivo de evaluar las caracteristicas tanto clinicas como de los tratamientos previos. Resultados. Entre los pacientes con infeccion por VHC que fueron analizados durante la primera parte del estudio, se observo que el genotipo 1 del VHC era el mas frecuente (con una prevalencia del 76,6%), predominando el subtipo 1b (69,8%) seguido de los genotipo 3 (12,3%) y genotipo 4 (7,4%). En la segunda parte del estudio se observo que el 44% de los pacientes infectados por genotipo 1 del VHC presentaban un grado de fibrosis F3/F4. Un 15,9 % de los pacientes no habian sido previamente tratados y un 50,8% habian fracasado a un tratamiento previo y en ese momento no recibian ningun tra- tamiento. Un 14,5% de los pacientes habian presentado previamente respuesta viral sostenida (RVS) tras terapia con interferon y ribavirina y durante el punto de corte de estudio se encontraban bajo tratamiento el 18,8% de los pacientes en seguimiento. En la segunda fase, un total de 713 pacientes (81,2% de la poblacion evaluada) no estaba recibiendo tratamiento, debido fundamentalmente a la prevision de llegada de nuevos farmacos (41,8%), a que ya estaban en RVS (17,8%) o a la ausencia de respuesta a las terapias disponibles en el momento del estudio (9,5%). Conclusiones. El genotipo mas prevalente del VHC en Espana es el genotipo 1, predominantemente 1b. El perfil de paciente mas frecuente fue el que presentaba fibrosis avanzadas o cirrosis, principalmente en pacientes aun no curados. EnglishIntroduction. To assess the clinical profile and management of patients with hepatitis C (HCV) infection in an observational study in Spanish hospitals. Methods. The study included an initial cross-sectional phase (study phase I), in which investigators at 48 hospitals from 14 Spanish regions collected data from approximately 20 consecutive patients each (a total of 1,000 patients) to assess the general features of HCV-infected patients of any genotype. During the second phase (study phase II), data from 878 patients that were infected exclusively with genotype 1 HCV were assessed retrospectively. Eight pre-defined clinical profiles were established, in order to assess clinical and previous treatments characteristics. Results. Among the HCV-infected individuals that were analysed during the first part, HCV genotype 1 was found to be predominant (with a prevalence of 76.6%), prevailing the subtype 1b (69.8%), with other significant groups infected by genotype 3 (12.3%) and 4 (7.4%). In the second part of the study, 44% of the HCV genotype 1-infected patients were at a F3/F4 fibrosis stage. 15.9% had never been treated, and previously unsuccessfully treated patients that were no longer receiving anti-HCV treatment accounted for 50.8% of cases. Individuals with a sustained virologic response (SVR) to previous dual therapies (based on Interferon and Ribavirin) were only 14.5% and patients under treatment during the study accounted for the remaining 18.8%. A total of 713 patients (81.2%) in the second phase were not receiving any type of therapy over the period analysed, mainly due to the anticipation of new anti-HCV drugs (41.8%), SVR achievement (17.8%) and unresponsiveness to therapies available at the time of the study (9.5%). Conclusions. HCV genotype 1, predominately 1b, is the most prevalent type in Spain. Advanced fibrosis or cirrhosis is frequent in this group, mainly patients not yet cured.

M30/CK18-cleavage staining, indicators of hepatocyte apoptosis. Indicators of oxidative stress, including the accumulation of 4-HNEprotein adducts and JNK phosphorylation, were also increased. In contrast, mice deficient in MLK3 were protected from ethanolinduced increases in plasma ALT/AST, pro-inflammatory cytokines and hepatic protein expression of RIP3. Ethanol-induced JNK phosphorylation and oxidative stress were also attenuated in MLK3deficient mice. However, MLK3-deficiency did not affect ethanolinduced steatosis or hepatocyte apoptosis. Conclusions: Taken together, these results suggest that MLK3 participates in the development of ethanol-induced oxidative stress, activation of JNK and induction of necroptotic programmed hepatocyte death. Pharmacological intervention of this pathway could be targeted as a potential therapeutic strategy to suppress necroptosis-induced inflammation and hepatocyte injury in patients with ALD.

Background and study aims : There is little information on the incidence of autoimmune hepatitis (AIH) because on many occasions the disease can progress asymptomatically, different diagnostic criteria have been proposed during the last 20 years, and many epidemiological studies are based on retrospective clinical series. The aim of this study was to determine the incidence of AIH in the province of Valencia, Spain, during the year 2003.Patients and Methods : The Services of Gastroenterology of eight acute-care reference hospitals in the province of Valencia, Spain, covering 1,774,736 inhabitants over 14 years of age, participated in a prospective study. All newly diagnosed patients with AIH between January 1, 2003 and December 31, 2003 were eligible. The diagnosis was based on criteria of the International Autoimmune Hepatitis Group revised in 1999.Results : There were 19 new cases of AIH, 18 females and I male [mean (SD) age of 54.3 (11.2) years, range 23-73]. Incidence peaked in the 45-54 year age group. Eighteen cases were classified as AIH type 1 and one case as AIH type 2. The incidence rate of AIH for the year 2003 in people older than 14 years of age was 1.07 new cases per 100,000 inhabitants, with 1.96 cases per 100,000 inhabitants in females and 0.12 cases per 100,000 inhabitants in males.Conclusions : The 2003 annual incidence of AIH in Valencia, Spain, was similar to that reported in other European countries. AIH occurred more frequently in women and in the 45-54 year age group, type I being the most common. (Acta gastroenterol. belg., 2009. 72, 402-406).

Sr. Director: La hepatitis autoinmunitaria es una hepatopatia inflamatoria cronica y progresiva de etiologia desconocida, se asocia a autoanticuerpos circulantes e hipergammaglobulinemia, y responde habitualmente al tratamiento inmunosupresor1. Puede afectar a ambos sexos y a todas las edades. En individuos predispuestos geneticamente se produce una reaccion inmunitaria aberrante contra autoantigenos hepaticos2, y en ocasiones intervienen factores externos, como infecciones viricas y tratamientos farmacologicos, que actuan como inductores. El efalizumab es un anticuerpo monoclonal de origen recombinante que actua inhibiendo la actividad de los linfocitos T, especificamente a la subunidad CD11a del LFA-1 (antigeno asociado a la funcion linfocitaria), y que se ha utilizado en el tratamiento de la psoriasis. En su ficha tecnica se indica que el 4\u20136% de los pacientes tratados con efalizumab presenta elevaciones de fosfatasa alcalina (FA) y alanina-aminotransferasa (ALT) de hasta 3 veces el limite superior de la normalidad, que se normalizan al interrumpir el tratamiento3, y se ha comunicado un caso de hepatitis idiopatica4. Ademas, puede producir trombocitopenia y anemia hemolitica autoinmunitarias4. Su comercializacion se ha suspendido recientemente tras la notificacion de casos de leucoencefalopatia multifocal progresiva. Presentamos aqui un caso de hepatitis autoinmunitaria probablemente inducida por efalizumab. Se trata de un mujer de 55 anos de edad, que en junio de 2007 comenzo tratamiento con efalizumab en dosis de 50mg/semana subcutanea por psoriasis en placas que presentaba desde los 25 anos, con afectacion ungueal. No tenia ningun otro antecedente de interes y no bebia alcohol ni tomaba ninguna otra medicacion. La bioquimica hepatica inmediatamente antes de comenzar...

Objective: the clinical phenotype of autoimmune hepatitis (AIH) varies among geographical areas. The aim of this study is to determine the salient features of AIH in adult patients from the province of Valencia, Spain.Material and methods: eighty-one patients with AIH attended to in eight acute-care hospitals between 1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated prospectively. Data from patients currently attending follow-up visits and diagnosed before 2003 were collected retrospectively.Results: a total of 94% of patients were females. Forty-three percent were asymptomatic, 27% had acute hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases. Type 2 AIH was more frequent in younger patients, and presented with an acute pattern. One third of patients had cirrhosis at onset. Patients with cirrhosis were older than 60 years more frequently. Immunosuppressants were given to 57 patients, with complete or partial remission in 87.7%. There were no significant differences in response to immunosuppression according to presentation pattern or AIH subtype.Conclusions: AIH in Valencia was predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25% of patients another autoimmune disease coexisted. At the time of diagnosis one third of patients had cirrhosis, particularly those over 60 years.

Because of its unpredictable behavior, renal cell carcinoma is one of the most controversial neoplasms. On the one hand, patients frequently show metastases at diagnosis because of its slight manifestations, while on the other, the neoplasm can remain stable after nephrectomy and can then metastasize many years later. When this happens, the metastases usually involve more than 2 organs. The most frequent sites of metastases are the lung and lymph nodes, followed by the bones and liver, while duodenal involvement is rare. Indeed, intestinal metastases are found in only 2% of autopsies and of these, renal cell carcinoma metastases account for 7.1%. We present a case of a solitary late recurrence presenting as upper gastrointestinal bleeding 19 years after nephrectomy for clear cell renal carcinoma.

Because of its unpredictable behavior, renal cell carcinoma is one of the most controversial neoplasms. On the one hand, patients frequently show metastases at diagnosis because of its slight manifestations, while on the other, the neoplasm can remain stable after nephrectomy and can then metastasize many years later. When this happens, the metastases usually involve more than 2 organs. The most frequent sites of metastases are the lung and lymph nodes, followed by the bones and liver, while duodenal involvement is rare. Indeed, intestinal metastases are found in only 2% of autopsies and of these, renal cell carcinoma metastases account for 7.1%. We present a case of a solitary late recurrence presenting as upper gastrointestinal bleeding 19 years after nephrectomy for clear cell renal carcinoma.

Thirteen cases of autoimmune hepatitis (AIH) were diagnosed from 1990 to 2003 in the area of the Hospital de Sagunto (Valencia, Spain), which attends a population of 112,003 inhabitants aged more than 14 years (54,622 males and 57,381 females). The diagnostic criteria of the International Autoimmune Hepatitis Group were used and patients who, despite having a probable diagnosis of AIH, presented hepatitis C virus infection were excluded. The diagnosis was probable in one patient and definitive in 12. All patients, 11 females and two males aged 45.9 12.2 years (range: 28-66), were classified as AIH type 1. Among the population aged more than 14 years, the mean annual incidence of AIH was 0.83 cases/100,000 inhabitants (95% CI, 0.44-1.42) (range: 0-2.68), showing a significant trend to increase (b = 0.132; p = 0.019). The incidence was higher in women than in men (RR = 5.24; 95% CI, 1.16-23.62). The mean annual incidence was 1.37 (95% CI, 0.68-2.46) (range: 0-3,49) in women and was 0.26 (95% CI, 0.02-0.96) (range: 0-1.83) in men. By age, the maximum mean annual incidence was observed in the group aged 55-64 years (1.6 cases/100,000 inhabitants). The prevalence of AIH in September 2003 was 11.61 cases/100,000 inhabitants aged more than 14 years (95% CI, 6.78-19.86). The prevalence was 3.66 (95% CI, 1-13.35) in men and was 19.17 (95% CI, 10.70-34.33) in women.

In patients with Wilson's disease and neurological manifestations, treatment with D-penicillamine can cause worsening of neurological symptoms, usually in the first few weeks of treatment. Because the neurological damage can be severe and irreversible, the use of D-penicillamine is controversial, and several authors believe that it should be avoided. Studies of the use of ammonium tetrathiomolybdate as an alternative chelating agent for the initial treatment of neurologic Wilson's disease are still in the experimental phase. Published experience on the simultaneous use of trientine, another chelating agent, and zinc, which blocks intestinal absorption of copper, is promising but limited. We present the case of a 17 year-old boy with severe neurologic Wilson's disease that had first presented six years previously. The patient showed a complete recovery after six months of treatment with a combination of trientine and zinc acetate.

En los pacientes con enfermedad de Wilson y afectación neurológica, la utilización de D-penicilamina produce con frecuencia empeoramiento de los síntomas neurológicos, habitualmente en las primeras semanas de tratamiento. Dado que el deterioro neurológico puede ser grave e irreversible, su uso es controvertido y algunos autores lo desaconsejan claramente. Se ha planteado que el tetratiomolibdato amónico es la mejor alternativa en estos pacientes, pero este tratamiento se encuentra todavía en fase experimental. La experiencia disponible con la combinación de trientina, un agente cupriurético, y sales de cinc, que impiden la absorción intestinal del cobre, aunque prometedora, es muy limitada. Presentamos el caso de un varón de 17 años de edad con enfermedad de Wilson y afectación neurológica grave de 6 años de evolución, con respuesta favorable y recuperación completa tras 6 meses de tratamiento combinado con trientina y acetato de cinc. In patients with Wilson's disease and neurological manifestations, treatment with D-penicillamine can cause worsening of neurological symptoms, usually in the first few weeks of treatment. Because the neurological damage can be severe and irreversible, the use of D-penicillamine is controversial, and several authors believe that it should be avoided. Studies of the use of ammonium tetrathiomolybdate as an alternative chelating agent for the initial treatment of neurologic Wilson's disease are still in the experimental phase. Published experience on the simultaneous use of trientine, another chelating agent, and zinc, which blocks intestinal absorption of copper, is promising but limited. We present the case of a 17 year-old boy with severe neurologic Wilson's disease that had first presented six years previously. The patient showed a complete recovery after six months of treatment with a combination of trientine and zinc acetate.