创建MAFLD防治新模式,合力推进分层全程管理

正代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)又称非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD),是遗传易感和营养过剩个体发生的与代谢功能障碍相关的脂肪性肝病~([1])。随着肥胖和代谢综合征的流行,MAFLD现已取代慢性乙型肝炎成为我国最常见的慢性肝病~([2])。亚洲地区的总体患病率为29.6%,其中我国大陆普通人群患病率为29.8%~([3])。临床上,     

从非酒精性脂肪性肝病到代谢相关脂肪性肝病的变迁

非酒精性脂肪性肝病(NAFLD)是全球范围最常见的慢性肝病,且进展至肝纤维化、肝硬化、肝癌等不良结局加重社会医疗负担。NAFLD特征是肝脏脂肪沉积和炎症,近40余年以来一直是一个排他性诊断,随着研究不断地深入,2020至2023年期间经历了两次更名,从代谢相关脂肪性肝病(MAFLD)到代谢功能障碍相关脂肪性肝病(MASLD)。本文讨论了目前对NAFLD/MAFLD/MASLD特征的对比、临床和研究问题,旨在提高我们对脂肪性肝病(SLD)的全面理解。     

代谢相关脂肪性肝病发病机理及治疗的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)是一种以肝内脂质沉积为特征的慢性肝病,目前已更名为代谢相关脂肪性肝病(metabolic associated fatty liver disease, MAFLD)。近年来MAFLD发病率逐步提升,对医疗系统的负担持续增加,在治疗方面尚无特效药物。本研究通过查阅相关文献,概述了影响MAFLD发病的相关机制,归纳了MAFLD治疗方法的当前进展,为临床治疗MAFLD提供理论基础。     

MAFLD、NAFLD与慢性肾脏病的研究进展

越来越多的证据表明，非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)不仅是全球范围内临床最常见的慢性肝病，且与慢性肾脏病(chronic kidney disease, CKD)的发病风险增加独立相关。2020年国际专家小组建议将NAFLD更名为代谢相关脂肪性肝病(metabolically related fatty liver disease, MAFLD),新的更名必然需要更多的真实世界研究证据予以评估。由于MAFLD和NAFLD的诊断标准不同，所以二者与CKD的关系必然也存在差异。本文主要就NAFLD/MAFLD与CKD患病的风险分析、NAFLD/MAFLD与CKD的关联机制、MAFLD/NAFLD在筛查CKD方面的差异性进行论述，并强调在临床实践中需要以多学科协作和以人为中心的模式来管理MAFLD/NAFLD合并CKD的患者。     

重视代谢相关脂肪性肝病的特征与预后临床研究*

非酒精性脂肪性肝病(NAFLD)是与胰岛素抵抗和遗传易感密切相关的以肝细胞大泡性脂肪变为病理特征的慢性代谢应激性肝脏疾病,疾病谱主要包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)及其相关的肝硬化和肝细胞癌(HCC)[1]。鉴于绝大多数NAFLD患者是肥胖症、2型糖尿病(T2DM)、代谢综合征累及肝脏的病理学表现,2020年国际专家小组将NAFLD更名为代谢功能障碍相关脂肪性肝病(MAFLD),亚太地区肝病协会、拉丁美洲肝病协会随后正式发布MAFLD诊疗指南,中东和北非肝病专家组、中华医学会肝病学分会和全球不少专家对NAFLD的更名和新的术语及其工作定义持赞成态度[2-6]。     

基于“脾主为胃行其津液”理论以行气祛湿活血法论治代谢相关脂肪性肝病

<正>于2020年国际专家共识声明将代谢相关脂肪性肝病(MAFLD)定义为肝脂肪沉积并伴有超重/肥胖、存在2型糖尿病或合并代谢紊乱^[1]。在术语上批准由代谢相关脂肪性肝病(MAFLD)取代之前的非酒精性脂肪性肝病(NAFLD)，强调了代谢失调是本病不容忽视的环节，本文以MAFLD替代NAFLD进行阐述。近年来，随着人们生活方式及饮食结构的改变，MAFLD影响世界上超过四分之一的人口，造成了严重的健康及经济负担。MAFLD包括一系列组织学异常，可由单纯肝脂肪变性逐步向肝纤维化及肝硬化进展；另则MAFLD有促进2型糖尿病、心血管疾病及慢性肾病等全身系统并发症的风险，是常见的慢性肝脏疾病之一，西医单一靶点药物治疗有其局限性^[2,3]。中医药因其多成分、多途径、多靶点特点，在对本病防治上有其优势。     

肠源性内毒素血症与代谢相关脂肪性肝病研究进展

代谢相关脂肪性肝病(metabolic-associated fatty liver disease, MAFLD)也称为非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD),是代谢综合征在肝脏的表现。MAFLD常与肥胖、糖尿病和高血压等疾病合并发生,按病理严重程度可分为脂肪肝、肝炎和肝硬化等阶段。     

慢性乙型病毒性肝炎合并非酒精性脂肪肝:老问题新发现

<正>2020年国际脂肪肝专家小组提出,用代谢相关脂肪性肝病(metabolic dysfunctional-associated fatty liver disease,MAFLD)取代非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD),且一致认为MAFLD相比NAFLD是更合适的研究术语。NAFLD的诊断需要排除乙型肝炎病毒(HBV)感染,MAFLD的诊断不需要,因此相当数量的HBV感染合并肝脏脂肪变性病例会被诊断为MAFLD。根据MAFLD的定义,HBV和AFLD(HBV-AFLD)将成为MAFLD的两个重要人群分布^[1]。由于目前大多数数据来自NAFLD相关研究,     

维生素D缺乏与代谢相关脂肪性肝病的关系

代谢相关脂肪性肝病(MAFLD)为全球第一大慢性肝病，但发病机制仍不明确，尚缺乏有效的治疗药物。介绍了MAFLD患者常伴有维生素D缺乏，维生素D可能通过影响糖脂代谢、炎症信号通路、免疫调节、肠道微生态等多种途径参与MAFLD的发生发展。提出维生素D有望成为MAFLD的治疗药物，临床上需关注MAFLD患者维生素D水平的监测和管理，但其内在机制、具体补充剂量及疗程亟待深入探索。     

非酒精性脂肪性肝病合并代谢并发症患者规范治疗与管理

正非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD),现有更名为代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)~([1]),是我国乃至世界最主要的慢性肝脏疾病,累及超过全球26%以上的总人口~([2,3])。大数据显示MAFLD患病率仍处于持续上升阶段,并且年轻化、大众化趋势日益显著~([3])。MAFLD不仅导致肝脏炎症、肝硬化和肝癌~([2]),还与糖脂代谢紊乱互为因果,引发一系列     

Coronavirus disease 2019 and non-alcoholic fatty liver disease

The coronavirus disease 2019(COVID-19) pandemic may present with a broad range of clinical manifestations, from no or mild symptoms to severe disease. Patients with specific pre-existing comorbidities, such as obesity and type 2 diabetes, are at high risk of coming out with a critical form of COVID-19. Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease, and, because of its frequent association with metabolic alterations including obesity and type 2 diabetes, it has recently been re-named as metabolic-associated fatty liver disease(MAFLD). Several studies and systematic reviews pointed out the increased risk of severe COVID-19 in NAFLD/MAFLD patients. Even though dedicated mechanistic studies are missing, this higher probability may be justified by systemic low-grade chronic inflammation associated with immune dysregulation in NAFLD/MAFLD, which could trigger cytokine storm and hypercoagulable state after severe acute respiratory syndrome coronavirus 2 infection. This review focuses on the predisposing role of NAFLD/MAFLD in favoring severe COVID-19, discussing the available information on specific risk factors, clinical features, outcomes, and pathogenetic mechanisms.     

Metabolic associated fatty liver disease: Addressing a new era in liver transplantation

Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease, is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation. The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management, including in the setting of liver transplantation. Patients with MAFLD present significant challenges in the pre-, peri- and post-transplant settings, largely due to the presence of medical comorbidities that include obesity, metabolic syndrome and cardiovascular risk factors. As the community prevalence of MAFLD increases concurrently with the obesity epidemic, donor liver steatosis is also a current and future concern. This review outlines current epidemiology, nomenclature, management issues and outcomes of liver transplantation in patients with MAFLD.     

Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions

In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut–liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.     

Metabolic dysfunction-associated fatty liver disease — How relevant is this to primary care physicians and diabetologists?

Metabolic-dysfunction associated fatty liver disease (MAFLD) is a newly introduced entity hoping to more precisely define fatty liver disease. Despite the controversies surrounding MAFLD, the definition is getting more widely accepted by the global liver-health community. MAFLD represents a cohort of patients enriched with more advanced liver disease, cardio-renal and metabolic complications with increased mortality. This review aims to provide all primary care physicians and diabetologists with a clinical management update from a non-hepatologist’s perspective, and a summary of important findings from recent studies to raise disease awareness and highlight the relevance of MAFLD to their daily clinical practice.     

代谢相关脂肪性肝病的内科治疗进展

代谢相关脂肪性肝病(MAFLD)是目前全球范围内最重要的肝病之一,其发病率呈逐年上升的趋势。总结了目前内科治疗MALFD的研究现状,其治疗方式包括生活方式的改变和个体化药物的治疗。其中生活方式的改变有饮食管理、运动干预、生物钟调整和心理干预,个体化药物治疗有胰岛素增敏剂、维生素E、减肥降脂药、保肝降酶药及中医药治疗等。同时,多学科协作的治疗方式是临床治疗MAFLD的大势所趋。     

Metabolic-associated fatty liver disease: New nomenclature and approach with hot debate

An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease. The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease(NAFLD) to metabolic(dysfunction)-associated fatty liver disease(MAFLD). This single-letter change, we believe, heralds the dawn of a new era in clinical practice and in clinical and basic research as well. The new nomenclature with the easily applicable approach has stimulated the enthusiasm...     

鼠李糖乳杆菌干预肠道菌群及脂质代谢治疗代谢相关性脂肪性肝病的研究进展

代谢相关性脂肪性肝病(metabolic associated fatty liver disease, MAFLD)现已成为全世界最常见的慢性肝病,发病率在逐年增加,目前无临床特效药,其发病机制复杂,主要涉及肥胖、肠道菌群、胰岛素抵抗、环境、遗传等。近年来,益生菌在预防和治疗MAFLD中被广泛研究,鼠李糖乳杆菌(Lactobacillus rhamnosus, LGG)属乳杆菌属的经典益生菌菌株。大量研究证明,LGG可通过调节肠道菌群、改善肠黏膜屏障及降低胆固醇改善MAFLD。本文主要阐述LGG干预MAFLD的相关可能机制。     

Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: Epidemiology,pathophysiologic mechanisms,and treatment considerations

The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease (MAFLD) has resulted in the reappraisal of epidemiological trends and associations with other chronic diseases. In this context, MAFLD appears to be tightly linked to incident chronic kidney disease (CKD). This association may be attributed to multiple shared risk factors including type 2 diabetes mellitus, arterial hypertension, obesity, dyslipidemia, and insulin resistance. Moreover, similarities in their molecular pathophysiologic mechanisms can be detected, since inflammation, oxidative stress, fibrosis, and gut dysbiosis are highly prevalent in these pathologic states. At the same time, lines of evidence suggest a genetic predisposition to MAFLD due to gene polymorphisms, such as the PNPLA3 rs738409 G allele polymorphism, which may also propagate renal dysfunction. Concerning their management, available treatment considerations for obesity (bariatric surgery) and novel antidiabetic agents (glucagon-like peptide 1 receptor agonists, sodium-glucose co-transporter 2 inhibitors) appear beneficial in preclinical and clinical studies of MAFLD and CKD modeling. Moreover, alternative approaches such as melatonin supplementation, farnesoid X receptor agonists, and gut microbiota modulation may represent attractive options in the future. With a look to the future, additional adequately sized studies are required, focusing on preventing renal complications in patients with MAFLD and the appropriate management of individuals with concomitant MAFLD and CKD.     

Macrophages in metabolic associated fatty liver disease

Metabolic associated fatty liver disease(MAFLD), formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries. The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death, but also to extrahepatic complications including cardiovascular disease, diabetes and chronic kidney disease. The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development. This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis, inflammation, fibrosis, and hepatocellular carcinoma, as well as for the extra-hepatic manifestations of MAFLD. We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes, hepatic stellate cells, and adipose tissue. We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.     

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.