Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy.

BACKGROUND Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model. METHODS Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining. RESULTS Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress. CONCLUSIONS Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.

Disastrous Portal Vein Embolization Turned into a Successful Intervention

Portal vein embolization (PVE) may be performed before hemihepatectomy to increase the volume of future liver remnant (FLR) and to reduce the risk of postoperative liver insufficiency. We report the case of a 71-year-old patient with hilar cholangiocarcinoma undergoing PVE with access from the right portal vein using a mixture of n-butyl-2-cyanoacrylate and ethiodized oil. During the procedure, nontarget embolization of the left portal vein occurred. An aspiration maneuver of the polymerized plug failed; however, the embolus obstructing portal venous flow in the FLR was successfully relocated into the right portal vein while carefully bypassing the plug with a balloon catheter, inflating the balloon, and pulling the plug into the main right portal vein.

Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels

Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. CONCLUSION In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH.

Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUND The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. AIMS To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. METHODS 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. RESULTS The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone. CONCLUSIONS Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension

BACKGROUND & AIMS Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats. METHODS Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin. RESULTS KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction. CONCLUSIONS Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.

Portal der Synagoge [Illustration] : (Fotografie)

Jacob S. Baars

Jakobs Traum und Ringen mit dem Engel [Illustration] : Trani, Kathedrale, Relief vom Portal, Romanisch, 13. Jahrhundert

Scan von Monochrom-Mikroform

Portal der Nibelungenhalle, Königswinter a. Rh., Drachenfels

Signatur des Originals: S 36/F08008

La Cordillera de los Andes : de muro a portal : visiones del otro a través del espacio

Nos hemos planteado los cambios de percepción de un accidente geográfico, como la cadena montañosa de los Andes, desde la Colonia hasta nuestros días, como un modo de comprender mejor nuestras maneras de ver el mundo. En efecto, la relación con el espacio avala universalmente la particularidad de las identidades, tal como ha sido estudiado por la antropología, entre otras disciplinas que se han ocupado de la problemática entre identidad y espacio. Nos interesa concentrarnos en las significaciones que le ha sido asignado al macizo andino en ciertas etapas, en uno y otro lado del mismo. La significación de muro que se le atribuye a la cordillera constituye una de las varias que existen y circulan en los textos literarios y no literarios. La relevancia que tiene ese punto de vista –el muro- se puede apreciar mejor en el campo de las relaciones internacionales entre ambos países. Sin embargo, existen otras relaciones espacio-representación que han alentado procesos integracionistas.

El DOI en las revistas científicas del portal SciELO

Se presenta una descripción del portal de revistas científicas SciELO y del identificador DOI a través de su alcance, año de creación, historia, administración, normativa, estructura, ISBN-A y fuentes de consulta. Se brinda información acerca de la aplicación del DOI en las citas bibliográficas: en los estilos APA y Vancouver y en las normas ISO 690 (ISO, 2010) y ABNT 6023 (ABNT, 2002). El trabajo se propuso explorar el grado de implementación del DOI en las revistas científicas disponibles en SciELO, identificar el lugar de visualización del DOI, conocer la cantidad de editores según el prefijo DOI, determinar la cantidad de títulos de revistas que incluyen en el sufijo el código ISSN e identificar grado de aplicación del DOI en los estilos y en las normas de citas bibliográficas disponibles dentro de SciELO. Se aplicó una metodología descriptiva donde los datos fueron recolectados a través de la observación directa de las páginas web de las 898 revistas vigentes disponibles entre los meses de diciembre de 2012 y enero de 2013 en el portal SciELO. Se concluye que: menos del 50 de los países que conforman SciELO en la actualidad están empleando el DOI en sus publicaciones; el código se visualiza fundamentalmente en los archivos HTML; sólo 30 de los 929 editores lo implementaron y que en la mayoría de los casos se incluye el ISSN dentro del sufijo del identificador y que, si bien SciELO utiliza el DOI en la totalidad de las citas de sus artículos, no lo hace en forma estricta tal como lo establecen las normas y los estilos