禁食疗法防治非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(NAFLD)是一种无过量饮酒史、以弥漫性肝细胞内脂肪变性为主要特征的临床病理综合征,与代谢综合征、肥胖症密切相关[1,2]。NAFLD是全球目前最常见的慢性肝病,是导致终末期肝病和肝细胞癌的主要原因之一[3]。治疗NAFLD的首要目标为减肥和改善胰岛素抵抗,生活方式干预是NAFLD患者的主要防治方法[4-6]。禁食疗法是生活方式干预中饮食干预的一种,大量研究报道,禁食疗法能够减轻体重、延缓衰老、调节免疫、防治肿瘤等。     

儿童非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是儿童最常见的肝病,与肥胖和代谢综合征关系密切。常规肝功能试验和肝脏超声检查有助于临床诊断,诊断NAFLD及其严重程度的金标准是肝活检,但需注意儿童和成人NAFLD有不同的肝组织学表现。NAFLD的治疗主要依靠改变生活方式,因为至今尚无安全有效的药物可推荐用于治疗儿童NAFLD。     

嗜黏蛋白阿克曼菌在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病（NAFLD）已成为全球最常见的慢性肝病,同时也是发生肝硬化和肝细胞癌的主要原因之一,因此及时遏止NAFLD的发生发展尤为重要,但由于其复杂的发病机制,目前尚无有效的根治手段。嗜黏蛋白阿克曼菌（Akk菌）作为新一代益生菌,能够改善机体代谢紊乱。越来越多的研究表明,Akk菌对代谢性疾病,尤其是NAFLD有潜在的治疗作用。因此,本文就Akk菌在NAFLD中的作用机制作简要综述,旨在为NAFLD的治疗改进和开创新疗法提供新思路。     

非酒精性脂肪性肝病与2型糖尿病、心血管疾病相关性

正非酒精性脂肪性肝病(NAFLD)是世界慢性肝病的最常见原因~([1])。一项基于美国人群的研究显示,在普通人群中NAFLD患病率约为30%~([2]);而入选的高危人群中其发病率升高,高危因素包括西班牙裔、肥胖、2型糖尿病(T2DM)和代谢综合征(MS)等~([1])。NAFLD不仅可促进T2DM的发生,而且是心血管疾病(CVD)的独立危险因素~([3])。因此,NAFLD与临床上所指的肝病有所不同。本文就NAFLD与T2DM、CVD关系进行综述。     

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。     

不同减肥措施对非酒精性脂肪性肝病转归的影响

肥胖是目前非酒精性脂肪性肝病(NAFLD)的常见原因,在全球其发病率近年来随着肥胖的盛行而迅猛增长.NAFLD与代谢综合征(MS)和胰岛素抵抗的关系密切.体重上升,尤其是腹腔内脂肪的增加是NAFLD和MS发生和进展的高危风险.对于肥胖相关的NAFLD患者,减肥是惟一有效的治疗方法,合理控制饮食,增加有氧运动,建立良好的心理行为是防治NAFLD的关键;目前还缺乏有关设计良好的药物和手术对肥胖相关的NAFLD的对照研究结论.     

非酒精性脂肪性肝病代谢组学与中医证候

非酒精性脂肪性肝病(NAFLD)发病率逐年增加,是全球范围最常见的肝病之一。代谢组学继承了基因组学、蛋白质组学的研究思想,对生物体内所有代谢物进行定量分析,探索代谢物与生理病理变化的相对关系,为研究中医药诊治NAFLD开辟了新途径。总结了代谢组学与中医证侯在NAFLD中的研究进展,为进一步探索NAFLD提供新的思路与方法。     

罗格列酮与非酒精性脂肪性肝病

脂肪性肝病(FLD)是遗传-环境-代谢应激相关因素所致的以肝细胞脂肪变性为主的临床病理综合征.FLD包括酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD).随着社会经济的发展,生活水平的提高,NAFLD已成为健康体格检查肝功能异常的主要原因.     

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。     

本期导读

随着人们生活习惯以及饮食结构的改变，非酒精性脂肪性肝病（NAFLD）已成为我国常见的慢性肝病之一，很多人在体检时被发现患有“脂肪肝”仍不以为然。NAFLD意味着什么？NAFLD与代谢综合征以及与胰岛素抵抗乃至胰岛素抵抗综合征的关系如何？本期我们特邀杨文英教授撰写专论“非酒精性脂肪肝是胰岛素抵抗的早期标志”，以大量临床研究结果说明NAFLD与代谢综合征密切相关，胰岛素抵抗程度与NAFLD病变进展相关，并以其研究组多年的研究结果说明NAFLD是胰岛素抵抗的早期标志，指出如果把NAFLD的防治意义提高到预防胰岛素抵抗早期形成的高度，定会把胰岛素抵抗综合征及其相关疾病推迟很多年。     

Original research: Implementation of a care bundle improves the management of patients with non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NAFLD ‘care bundle’ to standardise care; (3) to assess the impact of implementation of the NAFLD care bundle.MethodsA retrospective review was conducted to determine baseline management of patients with NAFLD attending seven hospitals in NEE. A care bundle for the management of NAFLD was developed including important recommendations from international guidelines. Impact of implementation of the bundle was evaluated prospectively in a single centre.ResultsBaseline management was assessed in 147 patients attending gastroenterology, hepatology and a specialist NAFLD clinic. Overall, there was significant variability in the lifestyle advice given and management of metabolic risk factors, with patients attending an NAFLD clinic significantly more likely to achieve >10% body weight loss and have metabolic risk factors addressed. Following introduction of the NAFLD bundle 50 patients were evaluated. Use of the bundle was associated with significantly better documentation and implementation of most aspects of patient management including management of metabolic risk factors, documented lifestyle advice and provision of NAFLD-specific patient advice booklets.ConclusionThe introduction of an outpatient ‘care bundle’ led to significant improvements in the assessment and management of patients with NAFLD in the NEE and could help improve and standardise care if used more widely.     

Nonalcoholic fatty liver disease in lean subjects: Prognosis,outcomes and management

Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. “Lean NAFLD” is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.     

Nonalcoholic fatty liver disease: from clinical recognition to treatment

Nonalcoholic fatty liver disease (NAFLD) is probably the most common spectrum of metabolic liver disease in the world, encompassing simple steatosis to steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD affects a significant part of the general population worldwide. The existing correlation between obesity and NAFLD in combination with the increase in the frequency of obesity in the developed world implies that the incidence and severity of NAFLD will increase in the near future. Newer data support the idea that NAFLD constitutes the more important cause of cryptogenic cirrhosis of the liver and a ground for the development of hepatocellular carcinoma. Liver biopsy remains the most specific and sensitive method to differentiate NAFLD, providing important information on the long-term prognosis of the patients. The ‘two hit’ hypothesis constitutes the currently prevailing theory for the development of NAFLD and nonalcoholic steatohepatitis. The first ‘hit’ is purported to be the increase of free fatty acids in hepatocytes, which results in a decrease of β-oxidation. The second step includes all mechanisms contributing to the development of necroinflammation and fibrosis. Currently, an effective treatment for patients with NAFLD does not exist. Improvement in liver histology remains the primary goal of any therapeutic approach in patients with NAFLD. Viewing NAFLD in the frame of the metabolic syndrome opens the possibility that both the onset of the disease and disease progression could be prevented by changes in lifestyle. Physical exercise and a low calorie diet in combination with the gradual loss of body weight represent the cornerstone for the management of NAFLD patients.     

Long‐term prognosis of nonalcoholic fatty liver disease: Is pharmacological therapy actually necessary?

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver injury, ranging from steatosis and steatohepatitis to cirrhosis. Reasons for the different natural course in individuals with NAFLD are still unclear. The aim of this study was to describe the natural course of disease in individuals with NAFLD who did not receive pharmacological therapy. Methods: A total of 27 individuals with NAFLD (male/female ratio: 10/17, mean age 49.7 years) were prospectively enrolled. Management after diagnosis consisted of establishment of an appropriate diet and exercise (walking and jogging) program, treatment of associated metabolic conditions such as diabetes and dyslipidemia, and discontinuation of potentially hepatotoxic drugs if the patient was taking these. Liver tests were performed at diagnosis and at 3‐month intervals during the follow‐up period. Mean follow‐up period was 43.3 months (range 36–49 months). Results: From baseline to the end of the follow‐up period, although there was no significant difference observed in terms of the mean body mass index, serum aminotransferase levels significantly improved (48.8 ± 29.9 U/L to 31.6 ± 16.0 U/L for aspartate aminotransferase [AST] and 66.3 ± 38.3 U/L to 39.6 ± 22.9 U/L for alanine aminotransferase [ALT]; P < 0.05). No significant differences in platelet counts, serum albumin level or prothrombin time were observed (P > 0.05). No patient developed signs of advanced liver disease during the follow‐up period. Conclusion: A treatment strategy comprising diet, exercise and management of associated metabolic conditions is associated with improvement in aminotransferases among patients with NAFLD. Further investigation is needed to examine the long‐term efficacy of this approach on liver histology and clinical outcomes.     

Fatty Liver: a Link to Cardiovascular Disease – Its Natural History,Pathogenesis, and Treatment

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in western society and is increasing in parallel with the worldwide epidemic of obesity. It exists in a simple form, steatosis, or a more complex and more dangerous form, steatohepatitis, and it is often but not always associated with the metabolic syndrome. NAFLD can progress to cirrhosis and hepatocellular carcinoma. It is responsible for the majority of cryptogenic cirrhosis cases. Increasingly, NAFLD and its more sinister form, steatohepatitis, have been linked to the increased incidence of cardiovascular disease (CVD) worldwide, independent of the metabolic syndrome. Death from CVD surpasses death from liver complications, but that is beginning to change as people are living longer with CVD. In this article, we will review nonalcoholic fatty liver disease and its epidemiology, prevalence, pathology, and link to CVD.     

Nonalcoholic fatty liver disease from a primary care perspective

Nonalcoholic fatty liver disease (NAFLD) affects up to one-third of the US population. Approximately one-fifth of patients with NAFLD have nonalcoholic steatohepatitis (NASH), characterized by hepatocyte damage and inflammation with or without fibrosis. NASH leads to greater risk of liver-related complications and liver-related mortality, with the poorest outcomes seen in patients with advanced fibrosis. NASH is also associated with other metabolic comorbidities and conveys an increased risk of adverse cardiovascular outcomes and extrahepatic cancers. Despite its high prevalence, NAFLD is frequently underdiagnosed. This is a significant concern, given that early diagnosis of NAFLD is a key step in preventing progression to NASH. In this review, we describe the clinical impact of NASH from the perspective of both the clinician and the patient. In addition, we provide practical guidance on the diagnosis and management of NASH for primary care providers, who play a pivotal role in the frontline care of patients with NASH, and we use case studies to illustrate real-world scenarios encountered in the primary care setting.     

非酒精性脂肪性肝病与代谢综合征指标变化的相关性分析

目的探讨中老年人群中非酒精性脂肪性肝病(NAFLD)与代谢综合征相关指标变化的关系。方法收集2010—2011年暨南大学附属第一医院40岁以上体检人群腹部B超检查的数据,用多因素Logistic回归分析体重指数(BMI)、空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、血尿酸(UA)的变化值与NAFLD变化的关系。结果 2年内男性组和女性组NAFLD检出率都在增加,男性新增NAFLD总检出率为13.7%,明显高于女性新增NAFLD检出率7.5%(P<0.05);男性和女性的NAFLD消减率都是5.5%,且峰值都在60岁年龄组;BMI变化值与新增NAFLD密切正相关,BMI变化值的OR=1.474(95%CI 1.184～1.811),而TG和FBG的变化值与新增NAFLD无相关性;TG和BMI的变化值与NAFLD的消减呈负相关,TG变化值的OR=0.653(95%CI 0.508～0.838),BMI变化值的OR=0.628(95%CI 0.460～0.857),而FBG变化值未发现与NAFLD消减有相关性。结论 BMI变化值与NAFLD发生有密切相关性,TG和BMI的变化值与NAFLD的消减呈负相关,是影响NAFLD变化的重要因素之一。     

多囊卵巢综合征患者非酒精性脂肪性肝病的发病情况及特点分析

目的探讨多囊卵巢综合征（PCOS）患者非酒精性脂肪性肝病（NAFLD）的发生情况和临床特点。方法对306例PCOS患者行基础内分泌、口服糖耐量试验及胰岛素释放试验、肝功、血脂、肝脏超声等检查。分析NAFLD的发病情况及特点。结果 NAFLD发生率为30.7%（94/306）;NAFLD发病率随体质量指数（BMI）和年龄的增加而升高。PCOS合并NAFLD者空腹血糖、空腹胰岛素、口服葡萄糖2h后血糖及胰岛素水平、稳态模型评估（HOMA-IR）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、TC、TG、LDL-C、BMI、腰围、腰臀比,均显著高于不合并NAFLD者（P均〈0.05）;而量化胰岛素敏感指数（QUICK）、HDL-C则显著低于不合并NAFLD者（P均〈0.05）。PCOS合并NAFLD者胰岛素抵抗、腹型肥胖、糖耐量异常、糖尿病、肝功异常、血脂异常、高血压病及代谢综合征的患病率显著高于不合并NAFLD者（P〈0.05）。结论 PCOS伴NAFLD发病率较高;其发病率与BMI和年龄呈正相关;PCOS伴NAFLD多存在胰岛素抵抗、代谢异常;超重及腹型肥胖是PCOS患者NAFLD的主要危险因素。     

Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA and many other parts of the world. Its prevalence continues to rise; currently affecting about one in four adults and 10% of children in the USA. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires an invasive liver biopsy with drawbacks of sampling and interpretation error. Clinical risk factors for NASH include diabetes and the metabolic syndrome; however, these are not sufficiently predictive of the condition by themselves. Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte cell death markers either alone or in combination with clinical risk factors are potential non-invasive diagnostic tools for the future. This review provides a concise overview of the role non-invasive diagnostic tools for the differentiation of fatty liver from NASH as well as for the determination of presence and extent of fibrosis.     

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low-grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti-osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti-osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.