Non-alcoholic fatty liver disease: an overview

Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.     

Risk of infections in non-alcoholic fatty liver disease: A nationwide population-based cohort study

Background and Aims

Previous literature suggests an association between non-alcoholic fatty liver disease (NAFLD) and infections. We aimed to determine the rate and risk of severe infections in NAFLD compared to the general population.

Methods

In this population-based cohort study, we used national registers to identify all patients with a hospital-based diagnosis of NAFLD in Sweden 1987–2020 (n = 14 869). The patients were matched with ≤10 comparators from the general population for age, sex, municipality, and calendar year (n = 137 145). Cox regression was used to estimate hazard ratios (HR) for infections in patients with NAFLD compared to comparators. Cumulative incidences were calculated while accounting for competing risks (non-infection death and liver transplantation).

Results

Severe infections leading to death or hospitalization occurred in 1990 (13.4%) patients with NAFLD and 9899 (7.2%) comparators during a median of 4.5 and 6.1 years of follow-up, respectively. The rate of severe infections per 1000 person-years was higher in patients with NAFLD (21.0) than comparators (9.1) independently of components related to the metabolic syndrome (adjusted HR 1.9, 95% CI = 1.8–2.0). Infection-related mortality was also higher in NAFLD compared to comparators (adjusted HR 1.8, 95% CI = 1.6–2.2). The 10-year cumulative incidence of severe infections was 16.6% (95% CI = 15.8–17.4) in NAFLD and 8.0% (95% CI = 7.8–8.2) in comparators.

Conclusion

NAFLD was associated with severe infections and infection-related mortality, independently of components associated with the metabolic syndrome. Increased clinical vigilance of severe infections in NAFLD may diminish the risk of premature death.     

非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病经历由非酒精性单纯性脂肪肝发展至非酒精性脂肪性肝炎和肝硬化或原发性肝癌的缓慢过程,并与心血管病的发生关系密切.本文针对非酒精性脂肪性肝病的流行病学、发病机制、诊断和治疗等的研究进展进行综述.     

非酒精性脂肪性肝病与代谢综合征相关性的临床研究

目的分析非酒精性脂肪性肝病与代谢综合征的关系。方法按住院顺序选择有随访资料病例共185例,将其分为四组（单纯脂肪肝组、单纯肥胖组、脂肪肝＋肥胖组、正常对照组）,在基线水平对四组出现代谢综合征情况进行横向比较。其次,在随访后再次对四组出现代谢综合征情况进行组内、组间比较。结果随访结束时,单纯脂肪肝组代谢综合征发病率明显高于正常对照组（P〈0.05）。结论非酒精性脂肪性肝病促进代谢综合征的发生,且不依赖于肥胖。     

非酒精性脂肪性肝病的诊断和治疗进展

随着非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)流行率的上升以及对其危害的全面认识,其诊断和治疗发展迅速。本文介绍了新的NAFLD病理学评分系统和病理学检查指征;在无创性诊断方面概述了肝脏脂肪变性、肝脏炎症和纤维化无创性诊断的现有方法及最新进展,以及疾病进展风险因素;在治疗方面,描述了饮食控制要点,并介绍了抗阻运动联合有氧运动和避免静坐的三联运动方式;在药物治疗方面,介绍了维生素E和吡格列酮2个重点药物的优缺点。最后,简述了以疾病分级为基础的检测和治疗策略。     

非酒精性脂肪性肝病国内外诊疗指南的区别及治疗展望

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗和遗传易感性密切相关的、肝脏脂肪过度堆积的代谢应激性肝脏损伤。据估计,目前世界上25%的人口被诊断患有NAFLD,对社会经济发展和人们的健康水平造成巨大影响。基于不同地区的生活习俗和人群基因差异,NAFLD在各国/地区的流行率不同,并且在NAFLD诊断标准和治疗方案上各国/地区诊疗指南给出的推荐也存在一定差异。该综述旨在对比国内外最新指南在NAFLD诊断与治疗方面的异同点,汇总最新诊疗手段研究进展,以期对NAFLD的临床诊疗提供借鉴。     

非酒精性脂肪肝与生长激素相关性研究

目的 探讨非酒精性脂肪肝（NAFLD）与生长激素（GH）的关系。方法入选NAFLD组38例,非NAFLD组42例．测定GH、腰围（Wc）、空腹血糖（FPG）、空腹胰岛素（Fins）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C）、高敏c反应蛋白（hs—CRP）,谷氨酸氨基转移酶（AIJrr）、γ-谷氨酰转肽酶（GGT）水平,计算体质量指数（BMI）、胰岛素抵抗指数（HOMA—IR）。结果NAFLD组GH、HDL—C水平显著低于非NAFLD组（P〈0．05）;NAFLD组BMI、WC、FPG、Fins、HOMA—IR、TG、hsCRP、AIJT、GGT水平显著高于非NAFLD组（P〈0．05）。GH、HDL—C与NAFLD呈负相关,WC、BMI、FPG、Fins、HOMA—IR、TG、hsCRP、ALT、GGT与NAFLD呈正相关。结论GH与NAFLD密切相关,低水平CH可能是NAFLD危险因素,与肥胖、胰岛素抵抗、血脂紊乱等共同参与了NAFLD的发生与发展。     

非酒精性脂肪性肝病与抑郁症的关系

非酒精性脂肪性肝病(NAFLD)已成为世界上最常见的慢性肝病之一。随着生物-心理-社会医学模式的发展,NAFLD患者的精神健康问题逐渐受到重视。近年来,NAFLD与精神性疾病,特别是抑郁症的相关研究越来越多,且证实二者存在明显的相关性。但二者相关性的共同病理生理机制仍不明确,孰因孰果及治疗方式亟待进一步研究。综述了NAFLD与抑郁症的关系、共同病理生理机制及治疗的研究进展。期望为两者关系更深层次的研究打下基础,有助于未来临床对这两种疾病进行联合预防和治疗。     

非酒精性脂肪性肝病发生及进展的危险因素

非酒精性脂肪性肝病(NAFLD)的患病率逐年增加,目前成为我国成年人中最常见的慢性肝病之一。NAFLD可由非酒精性肝脂肪变性进展为非酒精性脂肪性肝炎、肝硬化、肝细胞癌及NAFLD相关性心血管事件、死亡等重大疾病。现对NAFLD发生的危险因素以及进展为肝纤维化、肝硬化、肝癌、相关心血管事件和死亡等重大疾病的相关危险因素进行综述,以便进一步探讨NAFLD发生发展的机制,降低NAFLD的患病率,减缓NAFLD的进展程度,降低相关疾病的病死率。     

omega-3多不饱和脂肪酸治疗非酒精性脂肪性肝病的研究进展

随着人们生活方式和饮食结构的改变,非酒精性脂肪性肝病(NAFLD)发病率逐年上升,严重威胁人类健康。NAFLD疗法一直是基础和临床肝病研究的热门领域。近年来,诸多研究揭示omega-3多不饱和脂肪酸(ω3-PUFA)可促进脂肪酸氧化并改善肠道稳态,从而改善脂代谢和肝脏炎症,因而越来越多的临床研究开始将ω3-PUFA运用于NAFLD的治疗中。然而,ω3-PUFA治疗NAFLD的机制尚不明确,相关临床研究也存在一定局限性。主要介绍了ω3-PUFA在NAFLD中发挥的作用以及相关的临床研究结果,并进一步讨论ω3-PUFA治疗NAFLD尚需解决的问题。     

Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease: From nomenclature to clinical outcomes

As a result of the obesity epidemic, Nonalcoholic fatty liver disease(NAFLD) and its complications have increased among millions of people. Consequently, a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis; metabolic-associated fatty liver disease(MAFLD). This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rati...     

肝血窦内皮细胞在非酒精性脂肪性肝病发展中的作用

非酒精性脂肪性肝病(NAFLD)是以肝脏脂肪变、炎症和纤维化为主要表现的临床代谢综合征,日渐成为严重影响公众健康的常见慢性肝病。肝血窦内皮细胞(LSEC)是肝脏组织特化的血管内皮细胞,作为一道重要的血管屏障,其对肝脏细胞吸收和代谢源自肠道血液中的营养与物质成分发挥重要调节作用。介绍了NAFLD发生发展进程中LSEC毛细血管化、血管功能障碍及其参与调控肝脏炎症、血管生成、肝纤维化的研究进展。     

代谢相关脂肪性肝病肝外并发症研究进展与现状

代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)是作为描述这种疾病的一个更合适的总括述语,新的定义将代谢功能障碍列为肝病的重要病因,论证了MAFLD的高异质性,加快了向新治疗的转化路径.MAFLD的肝外并发症其发生率和相关疾病,远远超过肝病本身,严重威脅着人类健康.鉴于当前人们对其严重性认识不足,且对肝外并发病的疾病范围、发病机制、诊断的研究还不完善,尤其当前对其缺乏有效的药物治疗,有鉴于此本文就MAFLD肝外并发症研究现状与进展作一介绍与述评,与广大读者共享.     

Protein glutathionylation increases in the liver of patients with non-alcoholic fatty liver disease

Background and Aim:  Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis, where hepatocyte apoptosis is significantly increased correlating with disease severity. Protein glutathionylation occurs as a response to oxidative stress, where an increased concentration of oxidized glutathione modifies post-translational proteins by thiol disulfide exchange. In this study, we analyzed the protein glutathionylation in non-alcoholic fatty liver disease (NAFLD) and evaluated a potential association between glutathionylation, fibrosis, and vitamin E treatment.
Methods:  Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4–16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy.
Results:  Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis.
Conclusion:  Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis.     

Extracellular vesicles in fatty liver disease and steatohepatitis: Role as biomarkers and therapeutic targets

Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) are characterized by lipid deposition in hepatocytes in the absence or presence of excessive alcohol consumption, respectively, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) or alcoholic hepatitis (AH) and from mild fibrosis to cirrhosis. Fatty liver disease and steatohepatitis similarly occur in individuals who have both metabolic syndrome and excessive alcohol intake; therefore, the single overarching term metabolic associated fatty liver disease (MAFLD) has been proposed to better reflect these risk factors and the continuity of disease progression. Extracellular vesicles (EVs) are membrane-bound endogenous nanoparticles released into the extracellular space by a majority of cell types. Liver disease-related EVs contain a variety of cellular cargo and are internalized into target cells resulting in the transfer of bioinformation reflecting the state of the donor cell to the recipient. Furthermore, EV composition can be used to identify the degree and type of liver disease, suggesting that EV composition may be a useful biomarker. With regard to MAFLD, the presence of metabolic risk factors, such as insulin resistance, will be indicated by adipose tissue-derived EVs and with that comes the potential to use as a clinical monitor of overall metabolic status. However, the inhibition of specific EV composition may be difficult to implement as a real-world therapeutic approach. Current global evidence shows that mesenchymal stem cell (MSCs)-derived EVs (MSC-EVs) play an important role in regulating the immune response, which has spawned a clinical trial to treat liver disease.