Browsing by Author "Arrese, Marco"
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Item Evaluation of the chemopreventive potentials of ezetimibeand aspirin in a novel mouse model of gallbladderpreneoplasia(2020) Rosa, Lorena; Lobos-González, Lorena; Munoz Durango, Natalia; Garcıa, Patricia; Bizama, Carolina; Gomez, Natalia; Gonzalez, Ximena; Wichmann, Ignacio A.; Saavedra, Nicolas; Guevara, Francisca; Villegas, Jaime; Arrese, Marco; Ferreccio, Catterina; Alexis M. Kalergis, Alexis M.; Miquel, Juan Francisco; Espinoza, Jaime A.; Roa, Juan C.Gallbladder stones (cholecystolithiasis) are the main risk factor for gallbladder cancer (GBC), a lethal biliary malignancy with poor survival rates worldwide. Gallbladder stones are thought to damage the gallbladder epithelium and trigger chronic inflammation. Preneoplastic lesions that arise in such an inflammatory microenvironment can eventually develop into invasive carcinoma, through mechanisms that are not fully understood. Here, we developed a novel gallbladder preneoplasia mouse model through the administration of two lithogenic diets (a low- or a high-cholesterol diet) in wild-type C57BL/6 mice over a period of 9 months. Additionally, we evaluated the chemopreventive potentials of the anti-inflammatory drug aspirin and the cholesterol absorption inhibitor ezetimibe. Both lithogenic diets induced early formation of gallbladder stones, together with extensive inflammatory changes and widespread induction of metaplasia, an epithelial adaptation to tissue injury. Dysplastic lesions were presented only in mice fed with high-cholesterol diet (62.5%) in late stages (9th month), and no invasive carcinoma was observed at any stage. The cholesterol absorption inhibitor ezetimibe inhibited gallbladder stone formation and completely prevented the onset of metaplasia and dysplasia in both lithogenic diets, whereas aspirin partially reduced metaplasia development only in the low-cholesterol diet setting. This model recapitulates several of the structural and inflammatory findings observed in human cholecystolithiasic gallbladders, making it relevant for the study of gallbladder carcinogenesis. In addition, our results suggest that the use of cholesterol absorption inhibitors and anti-inflammatory drugs can be evaluated as chemopreventive strategies to reduce the burden of GBC among high-risk populations.Item Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review(WJG Press, 2014) Arab, Juan; Candia, Roberto; Zapata, Rodrigo; Muñoz, Cristián; Arancibia, Juan; Poniachik, Jaime; Soza, Alejandro; Fuster, Francisco; Brahm, Javier; Sanhueza, Edgar; Contreras, Jorge; Cuellar, Carolina; Arrese, Marco; Riquelme, ArnoldoAIM: To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS: NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS: A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form ofNAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION: Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events.Item Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports(Ediciones Medicina y Cultura, 2014) Sánchez, Adriana; di Pace, María; Brahm, Javier; Zapata, Rodrigo; Chirino, Ruby; Dávalos, Milagros; Méndez-Sánchez, Nahum; Arrese, Marco; Schinoni, María; Lucena, Isabel; Andrade, RaúlNTRODUCTION: Drug-induced liver injury (DILI) remains a major problem for drug development and represents a challenging diagnosis for clinicians. The absence of specific biomarkers for diagnosing DILI precludes the availability of reliable data on the epidemiology of the disease. In this study we aimed to describe the features of idiosyncratic hepatotoxicity reports in Latin American countries. MATERIAL AND METHODS: A literature search was performed using the online version of MEDLINE, EMBASE, Scopus, Google Scholar and specific data bases from Latin America (LA) (Scielo, Lilacs) to identify any case report or case series of published DILI from 1996 to 2012. From 1996 to 2012, a total of 176 patients with DILI were published in LA, involving 53 suspicious drugs. The median age in the adult population of these patients was 55 years (17-82) with prevalence of women (67%). Among main therapeutic classes, the rank order was led by non-steroidal anti-inflammatory (61 cases) and systemic antibacterial drugs (37 cases). Nimesulide was the individual drug responsible for the highest number of cases (53), followed by cyproterone acetate (18), nitrofurantoin (17), antituberculous drugs (13) and flutamide (12). Thirty two percent of published cases evolved to acute liver failure (ALF), and half of the subjects required liver transplantation or eventually died. CONCLUSIONS: This study represents the first structured attempt to assess the spectrum of DILI profile in LA. The establishment of a Latin American registry to collect prospective DILI cases using a standardized protocol will advance our knowledge about idiosyncratic DILI in this region.Item Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus(Baishideng Publishing Group, 2016) Arab, Juan; Claro, Juan; Arancibia, Juan; Contreras, Jorge; Gomez, Fernando; Muñoz, Cristian; Nazal, Leyla; Roessler, Eric; Wolff, Rodrigo; Arrese, Marco; Benitez, CarlosAIM To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension. METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded. RESULTS Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described. CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.