|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Studio delle modificazioni dell'integrità della barriera intestinale nei cirrotici avanzati sottoposti a profilassi di PVT con terapia con Enoxaparina.|
|Titolo in inglese||Study of modifications of intestinal barrier integrity in advanced cirrhotic patients in prophylaxis of PVT with Enoxaparin therpy.|
|Struttura||BIOSCIENZE E BIOTECNOLOGIE|
|Corso di studi||BIOTECNOLOGIE MEDICHE E FARMACEUTICHE (D.M. 270/04)|
|Data inizio appello||2011-12-12|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Lo scopo di questa tesi è di studiare gli eventi correlati alla traslocazione batterica e al microcircolo intestinale durante un protocollo di intervento anticoagulante in pazienti cirrotici con lo scopo di prevenire la trombosi venosa portale (PVT).
The purpose of this thesis is to study the events related with bacterial translocation and intestinal microcirculation during an interventional protocol of anticoagulation in cirrhotic patients aiming to prevent portal vein thrombosis (PVT). Portal vein thrombosis is a pathological condition characterized by the formation of a thrombus inside the portal vein or into its branches, that determines its total or partial obstruction. Portal vein thrombosis is determined by hepatobiliar and/or thrombophilic factors and it’s a common complication of decompensated cirrhosis. Pathogenetically, in advanced cirrhosis, because of liver structural derangement, there is an increase in blood pressure inside the portal vein, called “portal hypertension”. The progressive increase of portal hypertension leads to formation of esophageal varices but also to congestion of the lower intestine. This has important consequences, among all, possible derangement of the intestinal barrier, increased bacterial translocation and eventually, increased inflammation. This can lead to worsening of PVT, bleeding from gastroesophageal varices, refractory ascites, bacterial infections and also other compications that are typical of hepatic decompensation. It has been shown in the past that anticoagulation is able to reverse PVT (when it is not longstanding) and this leads to reduction of portal hypertension and clinical improvement. There are no studies in the literature on prevention of PVT and therefore we have decided to perform a randomized controlled prospective study (RCT) using a prophylactic dose of Enoxaparin versus no treatment to verify whether it was possible: 1) prevent PVT and 2) prevent decompensation. The studies reported in the thesis are those performed in the patients enrolled in the RCT to evaluate the consequences of portal hypertension in term of bacterial translocation and the possible ways to influence it. To do so, apart from collecting all the clinical and therapeutic data in order to analyze all the possible factors involved in the occurrence of PVT, two different type of analysis have been performed: a) markers of intestinal integrity (Intestinal-Fatty Acid Binding Protein: I-FABP and Interleukin 6: IL-6) and b) evaluation of circulating bacterial DNA. I-FABP is marker of enterocyte damage, indicative of bacterial translocation and IL-6, a proinflammatory cytokine, indicates an immune response against translocated bacterial antigens. Circulating bacterial DNA levels have been measured in serum. It’s a marker of bacterial translocation from intestine to systemic circulation through the portal vein. This marker has been measured by PCR amplification with specific primers for a common gene in all bacterial species, 16S rRNA. These tests showed that therapy determined improvement of enterocyte damage and decrease of percentage of patients with demonstrable bacterial DNA (at least during treatment). This suggests that integrity of the intestinal wall and improvement of microcirculation are critical event in the natural history of PVT and of cirrhosis itself.