Non alcoholic fatty liver disease or NAFLD is a disease with a large spectrum of liver injury that could appear in overweight or obese individuals with a metabolic syndrome. However, among overweight or obese, only a subset of individuals develops severe forms of NAFLD. Thus, the susceptibility of NAFLD is related to cofactors that could be protective or conversely noxious. Studies carried out in rodent models have demonstrated that the intestinal microbiota is a cofactor with a causal role in NAFLD. The bacterial patterns as well as the metabolites produced by intestinal bacteria are directly involved in the mediation of their effects, although the mechanisms are far from being fully identified. Changing intestinal microbiota by using fibers, prebiotics or probiotics can prevent or improve NAFLD in murine models. The translation of these data to human therapeutics is encouraging but remains limited. Indeed, there is clearly a dysbiosis associated with the different stages of NAFLD. The first clinical trials performed in patients to improve NAFLD showed beneficial effects although their analysis remains complicated given the many confounding factors, such as the use of metformin or proton inhibitors. A first clinical trial using a metabolite from Akkermansia muciniphila, suggests that new therapeutic approaches will emerge in the coming years based either on the modulation of the intestinal microbiota directly or on the modulation of intestinal microbiota targets. 相似文献
While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis. 相似文献
Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition . 相似文献
Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic associated fatty liver disease (MAFLD), is the commonest form of chronic liver disorder arising from metabolic dysregulation. It encompasses a wide spectrum of fatty liver phenotypes including isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is considered more likely to lead to grave clinical consequences such as cirrhosis and hepatocellular carcinoma, compared to simple steatosis. NASH is characterised by steatosis, inflammation, and damage to hepatocytes. Here, we present a case of a middle-aged gentleman with a background of infectious hepatitis who presented with NASH, with emphasis on terminology and histological assessment criteria of NAFLD and NASH. Reflection on and consistent effort to standardise terminology and assessment criteria will aid in addressing the scientific and clinical needs of NAFLD and NASH. 相似文献
Objectives: Exercise is an important part of disease management in patients with non-alcoholic fatty liver disease (NAFLD), but adherence to current exercise recommendations is poor. Novel low-volume sprint interval training (SIT) protocols with total training time commitments of ≤30 min per week have been shown to improve cardiometabolic risk and functional capacity in healthy sedentary participants, but the efficacy of such protocols in the management of NAFLD remains unknown. The aim of the present study was to examine whether a low-volume SIT protocol can be used to improve liver function, insulin resistance, body composition, physical fitness, cognitive function and general well-being in patients with NAFLD.Methods: In the present study, 7 men and 2 women with NAFLD (age: 45 ± 8 y, BMI: 28.7 ± 4.1 kg·m?2) completed a 6-week control period followed by 6 weeks of twice-weekly SIT sessions (5–10 × 6-s ‘all-out’ cycle sprints). Body composition, blood pressure, liver function, metabolic function, functional capacity, cognitive function and quality of life were assessed at baseline, following the control period, and following the SIT intervention.Results: Walking speed during the walk test (+12%), estimated V?O2max (+8%), verbal fluency (+44%), and blood platelet count (+12%; all p < 0.05) significantly increased during the control period. These measures remained significantly raised compared to baseline following the SIT intervention, but did not significantly change any further compared to the post-control time-point. Diastolic blood pressure decreased from 87 ± 10 to 77 ± 8 mm Hg from the end of the control period to the end of the SIT intervention (p < 0.05).Conclusion: This study does not support the use of 6 weeks of a low volume SIT protocol involving twice-weekly sessions with 5–10 × 6-s ‘all-out’ cycle sprints as an intervention for NAFLD disease management. 相似文献
Introduction: The endocannabinoid system is an important regulator of various physiological processes. Preclinical and clinical studies indicate that attenuation of the endocannabinoid system via antagonism of the type 1 cannabinoid receptor (CB1) is an excellent strategy to treat obesity, metabolic syndrome and associated disorders. However, centrally acting antagonists of CB1 also produce adverse effects like depression and anxiety. Current efforts are geared towards discovery and optimization of antagonists and modulators of CB1 that have limited brain penetration.
Areas covered: Several recent publications and patent applications support the development of peripherally acting CB1 receptor antagonists and modulators. In this review, recent patents and applications (2015–2018) are summarized and discussed.
Expert opinion: Approximately 30 new inventions have been reported since 2015, along with 3 recent commercial deals, highlighting the importance of this class of therapeutics. Taken together, peripherally acting CB1 receptor antagonists and modulators are an emerging class of drugs for metabolic syndrome, non-alcoholic steatohepatitis (NASH) and other important disorders where this receptor has been implicated. 相似文献