Papel del péptido insulinotrópico dependiente de glucosa en la programación nutricional del síndrome metabólico / Role of glucose-dependent insulinotropic peptide in the nutritional programming of metabolic syndrome

La restricción nutricional precoz ha sido asociada con una mayor incidencia de patologías relacionadas con el síndrome metabólico durante la edad adulta. Sin embargo, los mecanismos subyacentes que determinan el desarrollo de dichas patologías aún no se conocen en su totalidad. En el presente trabajo, se analizó el papel del péptido insulinotrópico dependiente de glucosa (GIP) en el desarrollo dichas patologías en un modelo de rata Wistar. Las ratas gestantes fueron alimentadas ad libitum (C) o sometidas a restricción nutricional (S) durante el embarazo y la lactancia, al final de la cual las crías fueron realimentadas con dieta grasa (CR, SR) durante 22 semanas. Tanto los machos como las hembras SR mostraron un fenotipo obesogénico caracterizado por hiperfagia, acumulación de grasa visceral e hipertrofia adipocitaria, de manera más pronunciada que la población CR. Los test de tolerancia oral a la glucosa mostraron que las hembras SR experimentaron intolerancia a la glucosa e hipersecreción de insulina y GIP. La administración del antagonista del receptor de GIP, (Pro3)GIP, a las hembras SR dio lugar a una significativa reducción del tejido adiposo y del tamaño adipocitario, junto a una mejora de la tolerancia a la glucosa y de la sensibilidad a la insulina. En conclusión, la exacerbada secreción de GIP parece representar el estímulo para la hipersecreción de insulina y el desarrollo de resistencia a la misma en las hembras SR, lo que sugiere que GIP jugaría un papel esencial en el desarrollo de alteraciones metabólicas asociadas a la rehabilitación nutricional

Early nutritional restriction has been associated with increased incidence of metabolic syndrome-associated pathologies in adulthood. However, the underlying mechanisms that determine the development of these diseases are not yet fully known. In the present work, we explored the relevance of glucose-dependent insulinotropic polypeptide (GIP) in the development of these pathologies in a model of Wistar rats. Two groups of dams were fed ad libitum (C) or food-restricted (U) during pregnancy and suckling. At that time, rats were refed a high-fat diet (HFD; CHF and UHF) for 22 weeks. Both male and female UHF rats showed an obese phenotype characterized by hyperphagia, visceral fat accumulation and adipocyte hypertrophy, which was more pronounced than in CHF rats. Oral glucose tolerance tests showed that female UHF rats experienced glucose intolerance, insulin hypersecretion and an exacerbated GIP secretion. Administration of the GIP receptor antagonist, (Pro3)GIP, to UHF female rats markedly reduced visceral fat mass and adipocyte hypertrophy, and these changes were accompanied by improvement of glucose tolerance and insulin sensitivity. In conclusion, the exacerbated production and secretion of GIP seems to represent the stimulus for insulin hypersecretion and insulin resistance shown by UHF female rats, suggesting that GIP may play a critical role in the development of metabolic disturbances related to nutritional rehabilitation

Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation

Introduction: The prevalence of portal vein thrombosis (PVT) in patients that have undergone liver transplantation (LT) is 9.7% (SD 4.5). The aim of our study was to determine the prevalence, assess the factors that are associated with PVT and clarify their association with prognosis in patients with liver cirrhosis (LC) and LT. Aims and methods: From 2005 to 2014, laboratory, radiological and surgical data were collected from patients with LC in our center who had undergone LT for the first time. esults: One hundred and ninety-one patients were included. The mean age was 55 (SD 9), 75.4% of patients were male and 48.7% had HCV. The Child-Pugh scores were A/B/C 41.9%/35.9%/25.5% and the MELD score was 15 (SD 6). Previous decompensations were: ascites (61.4%), hepatic encephalopathy (34.4%), variceal bleeding (25.4%), hepatocellular carcinoma (48.9%) and spontaneous bacterial peritonitis (SPB) (14.3%). The mean post-transplant follow-up was 42 months (0-113). PVT was diagnosed at LT in 18 patients (9.4%). Six patients were previously diagnosed using imaging tests (33.3%): 2 patients (11.1%) by DU and 4 patients (22.2%) by CT scan. All patients with PVT had DU in a mean time of 6 months before LT (0-44) and 90 patients (47.1%) had a CT scan in a median time of 6 months before LT (0-45). PVT was significantly related to the presence of SBP (33.3% vs 12.6%; p = 0.02) and lower levels of albumin (3.1g/dl vs 3.4g/ dl; p = 0.05). MELD was higher in patients with PVT (16.6 vs 14.9; p = 0.3). There were no significant differences with regard to the need for transfusion of blood components. Moreover, the surgery time was similar in both groups. PVT correlated with a higher mortality in the first 30 days (8.8% vs 16.7%; p = 0.2). Conclusion: Prior history of SBP and lower levels of albumin were identified as factors associated with PVT. The pre-transplant diagnosis rate is very low and the presence of PVT may have implications for short-term mortality (AU)

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Características clínicas del carcinoma hepatocelular en España. Comparación con el período 2008-2009 y análisis de las causas del diagnóstico fuera de cribado. Estudio de 686 casos en 73 centros / Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers

Antecedentes y objetivo: En 2010 publicamos que en España el 53% de los carcinomas hepatocelulares (CHC) se diagnostican fuera de programas de cribado, lo que conlleva una menor supervivencia. El objetivo del presente estudio es evaluar la situación actual y las causas del diagnóstico fuera de cribado. Material y métodos: Registro prospectivo entre el 1 de octubre de 2014 y el 31 de enero de 2015 en 73 centros asistenciales españoles de segundo/tercer nivel. Se registraron las características basales y el primer tratamiento de los tumores primarios hepáticos incidentales de ese período. Resultados: Se incluyeron 720 pacientes: CHC (n=686), colangiocarcinoma intrahepático (n=29), hepatocolangiocarcinoma (n=2), otros (n=3). Los pacientes con CHC fueron varones en el 82% de los casos; media de 67 años; cirrosis en el 87%; etiología: alcohol 35%, VHC 30%, alcohol y VHC 15%, enfermedad hepática por depósito de grasa 6%; estadio tumoral: BCLC-0 11%, A 43%, B 19%, C 16% y D 11%; tratamiento inicial: quimioembolización transarterial (23%), ablación percutánea (22%), tratamiento sintomático (20%), resección (11%), sorafenib (11%). Se diagnosticaron fuera de cribado 356 pacientes (53%). Los motivos principales fueron la ausencia de diagnóstico previo de hepatopatía (76%) y la mala adherencia al cribado (18%). Estos pacientes eran predominantemente varones (p<0,001), de etiología alcohólica (p<0,001), con consumo activo de alcohol (p<0,001) y se diagnosticaron en estadios más avanzados (p<0,001), recibiendo menos tratamientos radicales (p<0,001). Conclusiones: En España, la principal causa del diagnóstico de CHC fuera del cribado es la ausencia de diagnóstico previo de enfermedad hepática, principalmente en varones con consumo de alcohol. La detección de hepatopatía en población asintomática y la mejora de la adherencia al cribado son los principales aspectos para mejorar la detección precoz (AU)

Background and objective: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. Material and methods: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. Results: A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). Conclusions: In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC (AU)

Programa de uso compasivo con adefovir dipivoxil en España: valoración de su eficacia y estudio de las resistencias / Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis

Fundamento y objetivo: El tratamiento prolongado con lamivudina de los pacientes con hepatitis B crónica se asocia a la emergencia de resistencias. Los pacientes con resistencia a la lamivudina presentan una pérdida de la respuesta tanto bioquímica como virológica y una mayor progresión de la enfermedad hepática. El adefovir dipivoxil, un análogo de los nucleótidos, es eficaz en el tratamiento de los pacientes con resistencia a la lamivudina. El objetivo de este estudio ha sido evaluar la eficacia, la seguridad y las resistencias del adefovir dipivoxil en pacientes con hepatitis B crónica refractarios al tratamiento con lamivudina. Pacientes y método: Se ha incluido a 120 pacientes afectados de hepatitis B crónica y refractarios al tratamiento con lamivudina que recibieron tratamiento con adefovir dipivoxil. En 74 de ellos se realizó seguimiento durante 2 años. En todos los casos se determinó el ADN del virus de la hepatitis B por reacción en cadena de la polimerasa, y en los casos sin respuesta al tratamiento se estudió la presencia de resistencias a adefovir dipivoxil y lamivudina. Resultados: A los 2 años de tratamiento se observó respuesta virológica en el 54,1% de los pacientes, respuesta bioquímica en el 62,2% y eliminación del antígeno e de la hepatitis B en el 21%. Se detectaron resistencias a adefovir dipivoxil en el 20% de los casos, y las mutaciones detectadas con mayor frecuencia fueron A181V, A181T y N236T. La seguridad del fármaco fue excelente, pues se detectó sólo un efecto adverso relacionado con el tratamiento. Conclusiones: El tratamiento durante 2 años con adefovir dipivoxil en monoterapia en pacientes previamente refractarios a lamivudina se asocia a una alta tasa de respuesta bioquímica y virológica, con una seguridad excelente. La tasa de resistencias al adefovir dipivoxil a los 2 años fue del 20%

Background and objective: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. Patients and method: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. Results: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. Conclusions: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%