42 research outputs found

    Nuclear Receptors in Nonalcoholic Fatty Liver Disease

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    Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease

    Nuclear receptors in nonalcoholic Fatty liver disease

    Get PDF
    Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease

    Consenso Mexicano para el Tratamiento de la Hepatitis C

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    El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario. Abstract The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary

    Hepatology Highlights

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    Role of nonalcoholic fatty liver disease in hepatocellular carcinoma

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    Obesity and related disorders are a common cause of morbidity worldwide. Nonalcoholic fatty liver disease is the most important hepatic consequence of adipose accumulation. There is strong evidence of obesity-related disorders as risk factors for hepatocellular carcinoma and of nonalcoholic fatty liver disease as a cause of hepatocellular carcinoma, but it is apparently less important than other chronic liver diseases. Unfortunately, preventive measures are not well validated in the population of patients with NAFLD. In this review, we analyze the available information supporting the increased risk of hepatocellular carcinoma in obese patients and patients with nonalcoholic fatty liver disease, considering the epidemiological and basic research-derived evidence

    Hepatitis A virus infection in high-risk subjects

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    Original abstract: Background & Aims. Several outbreaks of hepatitis A affecting homosexual men have been reported in Europe. However, the prevalence of HIV infection in patients affected by hepatitis A has not been extensively studied and hepatitis A is not considered as an indicator disease for routine HIV testing.Methods. We retrospectively analyzed all adult cases of acute hepatitis A, reported by the National Institute of Infectious Disease “L. Spallanzani”, Rome-Italy, in 2002-2008. Data on HIV infection were obtained by chart review and cross-linkage with laboratory. Information on exposure to risk factors were collected from the standard questionnaire of the Local Health Unit.Results. We analyzed a total of 473 cases of hepatitis A, 368 (77.2%) males that accounted for 75% of all reported cases in Rome, aged 25-64 years (same gender distribution). During the study period, we diagnosed a high proportion of cases among male individuals (78%). Among the male patients, HIV serology was available for 203/368 (55.2%). The overall HIV prevalence was 15.2% (56/368); it was significantly associated with same gender sex and was significantly higher than that observed among patients with hepatitis B (4.0%).Conclusions. We found a high HIV prevalence, associated with same gender sex, among adult male patients diagnosed with hepatitis A in the period 2002-2008, except for 2006. Our data suggest that in a low incidence area for hepatitis A, with a constant high proportion of cases among male individuals, all individuals with acute hepatitis A should be routinely offered an HIV test

    Kinetics of the inflammatory response induced by free fatty acid accumulation in hepatocytes

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    Background. The information available on time and dose effects of the exposure of hepatocytes to free fatty acids (FFA) in vitro is controversial, and very few studies have assessed the hepatocyte inflammatory response in an in vitro model.Aim. To analyze the effect of treatment with FFA on cell viability and on the kinetics of cytokine expression using hepatic cell lines.Material and methods. Hepatic cell lines, IHH and HuH7, were cultured for 3 h, 6 h, 12 h and 24 h in an enriched medium with palmitic and oleic acids. The cytotoxicity of the FFA was assessed by the MTT test and the intracellular fat content determined cytofluorimetrically and by fluorescence microscopy using Nile Red staining. The expression of mRNA for interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α was assessed by real time reverse transcription-polymerase chain reaction (RT-PCR).Results. Treatment with 600 μM FFA did not affect the viability of either cell line despite a significant increase in the intracellular content of lipid droplets already evident after 3 h of treatment. A time- and dose-dependent upregulation of the expression of IL-6 and IL-8 mRNA was observed during the treatment at 3 and 24 h. In contrast, TNF-α mRNA expression was highly upregulated at 3 h after FFA exposure but returned to control values at 24 h. In conclusion, hepatocytes exposed in vitro for a short time to low FFA concentrations showed a significant upregulation of IL-6 and IL-8 to, and a rapid but transitory elevation of TNF-α
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