与肥胖、2 型糖尿病和肠道菌群失调有关的非酒精性脂肪肝

T. Bentsa
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引用次数: 0

摘要

随着肥胖症和 2 型糖尿病(T2DM)在全球的流行,非酒精性脂肪肝(NAFLD)的发病率也在不断上升。非酒精性脂肪肝增加了罹患 T2DM、心血管疾病和慢性肾病的风险。相反,肥胖和 T2DM 会增加非酒精性脂肪肝的发病率和死亡率。肥胖和 T2DM 的同步代谢功能障碍以及肠道菌群失调会直接激活先天性和适应性免疫反应,从而加剧肝脏和全身炎症。肠道菌群失调可导致非酒精性脂肪肝的出现和发展,并加速其发展为肝硬化和肝细胞癌。目前,基于饮食和运动的生活方式改变是治疗非酒精性脂肪肝患者的第一步。特定的饮食干预通过调节肠道-肝脏轴,有助于改善非酒精性脂肪肝。体育锻炼可提高胰岛素受体的敏感性,与饮食相结合可显著改善非酒精性脂肪肝合并肥胖和T2DM患者的生化指标和组织学指标。体育锻炼还能调节肠道微生物群的组成。特定的药物治疗主要针对非酒精性脂肪性肝炎、活检证实纤维化以及病情恶化风险较高的患者(年龄较大、T2DM、代谢综合征、丙氨酸氨基转移酶持续升高)。然而,目前治疗非酒精性脂肪肝的方法并不多。由于肠道微生物群与非酒精性脂肪肝的发病机制密切相关,因此使用益生菌、益生元或合成益生菌接触肠道微生物群以改善肝脏表型是合理的。在2023年6月21日至24日于维也纳举行的欧洲肝脏研究协会大会上,通过了非酒精性脂肪肝的新分类和命名方法。会议建议用 "代谢功能障碍相关性脂肪肝 "取代 "非酒精性脂肪肝"。这一诊断适用于确诊肝脏脂肪变性并具有肥胖、T2DM、胰岛素抵抗、高脂血症和动脉粥样硬化五种心脏代谢危险因素之一的患者。非酒精性脂肪性肝炎 "的概念已改为 "代谢功能障碍相关性脂肪性肝炎"。协调国际和国内研究这一病理学领域的专家的观点,对于临床实践和科学研究将具有重要意义。
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Nonalcoholic fatty liver disease associated with obesity and type 2 diabetes and gut dysbiosis
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM) worldwide. NAFLD increases the risk of T2DM, cardiovascular di­sease, and chronic kidney disease. Conversely, obesity and T2DM increase morbidity and mortality from NAFLD. Synchronous metabolic dysfunction in obesity and T2DM and gut dysbiosis exacerbate hepatic and systemic inflammation due to direct activation of innate and adaptive immune responses. Gut dysbiosis can contribute to the emergence and development of NAFLD, as well as acceleration of its progression to liver cirrhosis and hepatocellular carcinoma. Currently, lifestyle changes based on diet and exercise are the first step in the treatment of patients with NAFLD. Specific dietary interventions contribute to the improvement of NAFLD by modulating the gut-liver axis. Physical activity increases the sensitivity of insulin receptors, and in combination with diet leads to a reliably significant improvement in biochemical and histological indicators in patients with NAFLD combined with obesity and T2DM. Physical activity also modulates gut microbiota composition. Specific pharmacological treatment is performed mainly in patients with nonalcoholic steatohepatitis and biopsy-proven fibrosis, as well as a high risk of progression (older age, T2DM, metabolic syndrome, persistent elevation of alanine aminotransfe­rase). However, there are few available treatment options for NAFLD. Since gut microbiota is actively involved in the pathogenesis of NAFLD, exposure to it with probiotics, prebiotics or synbiotics in order to improve the liver phenotype is reasonable. At the congress of the European Association for the Study of the Liver, which took place in Vienna on June 21–24, 2023, a new classification and nomenclature of NAFLD was adopted. It was proposed to replace the term “nonalcoholic fatty liver disease” with the term “metabolic dysfunction-associated steatotic liver disease”. This diagnosis is established in patients with confirmed steatosis of the liver and one of five cardiometabolic risk factors: obesity, T2DM, insulin resistance, hyperlipidemia, atherosclerosis. The concept of “nonalcoholic steatohepatitis” has been changed to the concept of “metabolic dysfunction-associated steatohepatitis”. Coordination of the views of international and domestic experts in the field of studying this pathology will be important for clinical practice and scientific research.
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