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2024代谢相关（非酒精性）脂肪性肝病防治指南（全文）《代谢相关（非酒精性）脂肪性肝病防治指南（2024年版）》是对《非酒精性脂肪性肝病防治指南（2018更新版）》进行的修订，主要针对代谢相关脂肪性肝病的筛查和监测、诊断和评估、治疗和随访等临床问题提出了指导性建议。
指南推荐意见一览推荐意见1：代谢相关脂肪性肝病（MAFLD）是我国最常见的慢性进展性肝病，应该加强筛查和防治（B，1）。
推荐意见2：肥胖、2型糖尿病（T2DM）、代谢综合征（MetS）组分、过量饮酒、无症状性转氨酶增高等高风险人群应该筛查脂肪肝和纤维化（B，1）。
推荐意见3：MAFLD 患者应该筛查并监测肝纤维化（B，1）。
推荐意见4：合并进展期纤维化的MAFLD 患者应该筛查肝细胞癌（ HCC），明确诊断肝硬化时还应筛查食管静脉曲张和肝脏失代偿事件（B，1）。
推荐意见5：MAFLD 患者应该筛查并监测MetS 组分和T2DM（B，1）。
推荐意见6：MAFLD 患者应该筛查慢性肾脏病（CKD）和亚临床动脉硬化，并评估心血管病（CVD）风险（B，1）。
推荐意见7：MAFLD 患者应该坚持参加基于年龄分层的各种常见恶性肿瘤的筛查（C，1）推荐意见8：诊断MAFLD 基于以下 3 个标准：（1）影像学诊断脂肪肝和/ 或肝活检发现≥5% 肝细胞大泡性脂肪变性；（2）存在 1 项及以上MetS 组分；（3）排除过量饮酒、营养不良、肝豆状核变性等可能导致脂肪肝的其他原因（B，1）。
推荐意见9：酒精性肝病（ALD）和其他原因脂肪肝患者有肥胖和/或T2DM、MetS 时需要考虑合并MAFLD（C，1）。
推荐意见10：MAFLD 可以与慢性病毒性肝炎等其他类型肝病合并存在（B，1）。
推荐意见11：超声显像是影像学诊断脂肪肝以及筛查和监测HCC 的首选方法（B，1）。
推荐意见12：瞬时弹性成像检测的受控衰减参数/超声衰减参数（ CAP/ UAP）和肝硬度值（LSM）可以用于慢性肝病患者脂肪肝和肝纤维化的无创诊断与评估（B，1）。
!O"!代谢相关脂肪性肝病的内科治疗进展刘素彤１，２，苏凯奇１，赵晨露１，张丽慧１，２，赵文霞１，２１河南中医药大学第一临床医学院，郑州４５００４６；２河南中医药大学第一附属医院脾胃肝胆科，郑州４５００００摘要：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。
关键词：代谢相关脂肪性肝病；生活方式；药物疗法中图分类号：Ｒ５７５．５ 文献标志码：Ａ 文章编号：１００１－５２５６（２０２１）０４－０９４７－０４ＲｅｓｅａｒｃｈａｄｖａｎｃｅｓｉｎｍｅｄｉｃａｌｔｒｅａｔｍｅｎｔｏｆｍｅｔａｂｏｌｉｃａｓｓｏｃｉａｔｅｄｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅＬＩＵＳｕｔｏｎｇ１，２，ＳＵＫａｉｑｉ１，ＺＨＡＯＣｈｅｎｌｕ１，ＺＨＡＮＧＬｉｈｕｉ１，２，ＺＨＡＯＷｅｎｘｉａ１，２．（１．ＴｈｅＦｉｒｓｔＣｌｉｎｉｃａｌＭｅｄｉｃａｌＣｏｌｌｅｇｅｏｆＨｅｎａｎＵｎｉｖｅｒｓｉｔｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，Ｚｈｅｎｇｚｈｏｕ４５００４６，Ｃｈｉｎａ；２．ＤｅｐａｒｔｍｅｎｔｏｆＨｅｐａｔｏｌｏｇｙａｎｄＳｐｌｅｅｎ－Ｓｔｏｍａｃｈ，ＴｈｅＦｉｒｓｔＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａｌｏｆＨｅｎａｎＵｎｉｖｅｒｓｉｔｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，Ｚｈｅｎｇｚｈｏｕ４５００００，Ｃｈｉｎａ）Ａｂｓｔｒａｃｔ：Ｍｅｔａｂｏｌｉｃａｓｓｏｃｉａｔｅｄｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅ（ＭＡＦＬＤ）ｉｓｃｕｒｒｅｎｔｌｙｏｎｅｏｆｔｈｅｍｏｓｔｉｍｐｏｒｔａｎｔｌｉｖｅｒｄｉｓｅａｓｅｓｗｏｒｌｄｗｉｄｅ，ａｎｄｉｔｓｉｎｃｉｄｅｎｃｅｒａｔｅｉｓｉｎｃｒｅａｓｉｎｇｙｅａｒｂｙｙｅａｒ．ＴｈｉｓａｒｔｉｃｌｅｓｕｍｍａｒｉｚｅｓｔｈｅｃｕｒｒｅｎｔｒｅｓｅａｒｃｈｓｔａｔｕｓｏｆｍｅｄｉｃａｌｔｒｅａｔｍｅｎｔｏｆＭＡＦＬＤ，ｉｎｃｌｕｄｉｎｇｌｉｆｅｓｔｙｌｅｃｈａｎｇｅｓａｎｄｉｎｄｉｖｉｄｕａｌｉｚｅｄｄｒｕｇｔｒｅａｔｍｅｎｔ．Ｌｉｆｅｓｔｙｌｅｃｈａｎｇｅｓｉｎｃｌｕｄｅｄｉｅｔｍａｎａｇｅｍｅｎｔ，ｅｘｅｒｃｉｓｅｉｎｔｅｒｖｅｎｔｉｏｎ，ｂｉｏｌｏｇｉｃａｌｃｌｏｃｋａｄｊｕｓｔｍｅｎｔ，ａｎｄｐｓｙｃｈｏｌｏｇｉｃａｌｉｎｔｅｒｖｅｎｔｉｏｎ，ａｎｄｉｎｄｉｖｉｄｕａｌｉｚｅｄｄｒｕｇｔｒｅａｔｍｅｎｔｉｎｃｌｕｄｅｓｉｎｓｕｌｉｎｓｅｎｓｉｔｉｚｅｒ，ｖｉｔａｍｉｎＥ，ｗｅｉｇｈｔ－ｌｏｓｓａｎｄｌｉｐｉｄ－ｌｏｗｅｒｉｎｇｄｒｕｇｓ，ｌｉｖｅｒ－ｐｒｏｔｅｃｔｉｎｇａｎｄｔｒａｎｓａｍｉｎａｓｅ－ｌｏｗｅｒｉｎｇｄｒｕｇｓ，ａｎｄｔｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅｍｅｄｉｃｉｎｅｔｒｅａｔｍｅｎｔ．Ａｔｔｈｅｓａｍｅｔｉｍｅ，ｍｕｌｔｉｄｉｓｃｉｐｌｉｎａｒｙｔｒｅａｔｍｅｎｔｉｓｔｈｅｔｒｅｎｄｏｆｃｌｉｎｉｃａｌｔｒｅａｔｍｅｎｔｏｆＭＡＦＬＤ．Ｋｅｙｗｏｒｄｓ：ＭｅｔａｂｏｌｉｃＡｓｓｏｃｉａｔｅｄＦａｔｔｙＬｉｖｅｒＤｉｓｅａｓｅ；ＬｉｆｅＳｔｙｌｅ；ＤｒｕｇＴｈｅｒａｐｙＤＯＩ：１０．３９６９／ｊ．ｉｓｓｎ．１００１－５２５６．２０２１．０４．０４８收稿日期：２０２０－１１－２３；修回日期：２０２１－０１－１１基金项目：国家自然科学基金面上项目（８１４７３６５１）；河南省中医药科学研究专项课题（２０１８ＪＤＺＸ００５，２０１９ＪＤＺＸ２０５１）；河南省科技攻关计划项目（２０２１０２３１０４９５）作者简介：刘素彤（１９９１—），女，在读博士，主要从事中医药防治脾胃肝胆疾病的临床和基础研究通信作者：赵文霞，ｚｈａｏ－ｗｅｎｘｉａ＠１２６．ｃｏｍ 代谢相关脂肪性肝病（ｍｅｔａｂｏｌｉｃａｓｓｏｃｉａｔｅｄｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅ，ＭＡＦＬＤ）的患病率呈逐年上升的趋势［１］。
非酒精性脂肪性肝病国内外诊疗指南的区别及治疗展望
黎翔;陈弋;刘霞;孙旸
【期刊名称】《中国动脉硬化杂志》
【年(卷),期】2024(32)4
【摘要】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。
【总页数】8页(P347-354)
【作者】黎翔;陈弋;刘霞;孙旸
【作者单位】海军军医大学药学院
【正文语种】中文
【中图分类】R5
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,- . ＤＯＩ：１０．３９６９／ｊ．ｉｓｓｎ．１００１－５２５６．２０２３．０５．０２１非酒精性脂肪性肝病儿童肝组织病理特征分析刘 敏ａ，陈卫坚ａ，周峥珍ａ，覃小梅ｂ，文 容ａ，姜 楠ａ，匡林芝ａ，郑台青ａ，张丽琼ａ，李双杰ｂ湖南省儿童医院ａ．病理科，ｂ．肝病中心，长沙４１００００通信作者：李双杰，２２７３８５８９５１＠ｑｑ．ｃｏｍ（ＯＲＣＩＤ：００００－０００２－３７９２－６７９３）关键词：非酒精性脂肪性肝病；病理学，临床；儿童基金项目：湖南省卫生健康委科研项目计划（２０２２０６０１４２６７）Ｈｉｓｔｏｐａｔｈｏｌｏｇｉｃａｌｃｈａｒａｃｔｅｒｉｓｔｉｃｓｏｆｔｈｅｌｉｖｅｒｉｎｃｈｉｌｄｒｅｎｗｉｔｈｎｏｎ－ａｌｃｏｈｏｌｉｃｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅＬＩＵＭｉｎａ，ＣＨＥＮＷｅｉｊｉａｎａ，ＺＨＯＵＺｈｅｎｇｚｈｅｎａ，ＱＩＮＸｉａｏｍｅｉｂ，ＷＥＮＲｏｎｇａ，ＪＩＡＮＧＮａｎａ，ＫＵＡＮＧＬｉｎｚｈｉａ，ＺＨＥＮＧＴａｉｑｉｎｇａ，ＺＨＡＮＧＬｉｑｉｏｎｇａ，ＬＩＳｈｕａｎｇｊｉｅｂ．（ａ．ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｌｏｇｙ，ｂ．ＬｉｖｅｒＤｉｓｅａｓｅＣｅｎｔｅｒ，ＨｕｎａｎＣｈｉｌｄｒｅｎ’ｓＨｏｓｐｉｔａｌ，Ｃｈａｎｇｓｈａ４１００００，Ｃｈｉｎａ）Ｃｏｒｒｅｓｐｏｎｄｉｎｇａｕｔｈｏｒ：ＬＩＳｈｕａｎｇｊｉｅ，２２７３８５８９５１＠ｑｑ．ｃｏｍ（ＯＲＣＩＤ：００００－０００２－３７９２－６７９３）Ｋｅｙｗｏｒｄｓ：Ｎｏｎ－ａｌｃｏｈｏｌｉｃＦａｔｔｙＬｉｖｅｒＤｉｓｅａｓｅ；Ｐａｔｈｏｌｏｇｙ，Ｃｌｉｎｉｃａｌ；ＣｈｉｌｄＲｅｓｅａｒｃｈｆｕｎｄｉｎｇ：ＲｅｓｅａｒｃｈＰｒｏｊｅｃｔＰｌａｎｏｆＨｕｎａｎＰｒｏｖｉｎｃｉａｌＨｅａｌｔｈＣｏｍｍｉｓｓｉｏｎ（２０２２０６０１４２６７） 非酒精性脂肪性肝病（ｎｏｎ－ａｌｃｏｈｏｌｉｃｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅ，ＮＡＦＬＤ）已成为全球儿童发生率最高的慢性肝病［１－２］。
·指南与规范·DOI： 10.3969/j.issn.1001-5256.2023.10.010《2023年国际多学科专家共识：代谢相关脂肪性肝病和心血管疾病风险》摘译周晓东1a，田娜1b，郑明华1b，2，31 温州医科大学附属第一医院 a.心脏中心，心血管内科， b.感染内科，浙江温州 325000；2 温州医科大学肝病研究所，浙江温州 325000；3 浙江省慢性肝病重症化精准诊治与转化重点实验室，浙江温州325000通信作者：郑明华，***************.cn（ORCID： 0000－0003－4984－2631）摘要：代谢相关脂肪性肝病（MAFLD）是全球范围内常见的慢性肝病，影响全球超过四分之一的成年人口。
MAFLD特征是肝脏脂肪变性和代谢紊乱共存。
作为一种代谢功能障碍性疾病，MAFLD与心血管疾病（CVD）有着相似的发病机制。
这两种疾病都与肥胖、2型糖尿病和致动脉粥样硬化性血脂异常等公认的心血管危险因素密切相关。
越来越多的证据支持MAFLD与CVD之间存在密切联系。
然而，作为一种新兴的CVD危险因素，MAFLD与传统的CVD危险因素不同，仍待进一步研究。
在这一背景下，本共识使用德尔菲法则，通过两轮调查就MAFLD和CVD风险之间的联系达成一致意见，并探讨了MAFLD与CVD流行病学及临床特征的相关性，以及病理生理机制、监测和管理等一系列问题。
关键词：代谢相关脂肪性肝病；非酒精性脂肪性肝病；心血管疾病；共识基金项目：国家自然科学基金项目（82070588）；浙江省卫生厅高层次创新人才项目（2032102600032）Excerpt of an international multidisciplinary consensus statement on MAFLD and the risk of CVD （2023）ZHOU Xiaodong1a，TIAN Na1b，ZHENG Minghua1b，2，3.（1. a. Department of Cardiovascular Medicine，The Heart Center，b. Department of Infectious Diseases，The First Affiliated Hospital of Wenzhou Medical University，Wenzhou，Zhejiang 325000，China；2. Institute of Hepatology，Wenzhou Medical University，Wenzhou，Zhejiang 325000，China；3. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province， Wenzhou， Zhejiang 325000， China）Corresponding author： ZHENG Minghua，***************.cn（ORCID： 0000－0003－4984－2631）Abstract：Metabolic associated fatty liver disease （MAFLD） is a common chronic liver disease around the world， affecting more than a quarter of the adult population worldwide. MAFLD is characterized by the co-occurrence of hepatic steatosis and metabolic disturbance. As a metabolic disorder， MAFLD shares a similar pathogenesis with cardiovascular disease （CVD），and both diseases are closely associated with the well-established cardiovascular risk factors such as obesity，type 2 diabetes， and atherogenic dyslipidemia. An increasing amount of evidence has shown that MAFLD is closely associated with CVD； however， as a new risk factor for CVD， MAFLD differs from traditional risk factors for CVD， which requires further investigation.In this context，this consensus statement used the Delphi method to achieve a consensus on the association between MAFLD and the risk of CVD through two rounds of surveys and discussed the association between MAFLD and CVD in terms of epidemiological and clinical characteristics， as well as a range of topics including pathophysiological mechanisms，surveillance， and management.Key words：Metabolic （dysfunction）－Associated Fatty Liver Disease；Non－Alcoholic Fatty Liver Disease；Cardiovascular Diseases； ConsensusResearch funding：National Natural Science Foundation of China （82070588）；High Level Creative Talents from the Department of Public Health in Zhejiang Province （2032102600032）亚太肝病学会官方杂志Hepatology International在2023年在线正式发布了“代谢相关脂肪性肝病和心血管疾病风险的国际多学科专家共识”［1］。
doi：10.3969/j.issn.1005-0264.2021.06.004代谢相关脂肪性肝病的中西医诊疗思考与对策张国红1李晓东2°周亚娜徐曦2,3肖明中2M1•湖北省中医院徐家棚分院（湖北武汉，430061）2.湖北省中医院肝病研究所3.湖北省中医院中医肝肾研究及应用湖北省重点实验室摘要2020年5月，国际专家小组发布了《代谢相关脂肪性肝病的诊断和管理共识》，提出采用MAFLD取代现有命名“非酒精性脂肪性肝病（NAFLD）”的立场声明，进一步明确了MAFLD的临床诊疗指导意见。
本文就MAFLD的广泛疾病谱、治疗应答不佳、易感基因与表观遗传因素、医患对疾病认识不足等现状以及MAFLD的西医诊断评估进行阐述，并通过学习仝小林团队创建的脾痒理论，从代谢综合征（膏浊病）的整体角度思考中医肝癖（MAFLD）的病因病机，中医诊治MAFLD的优势等方面，探讨MAFLD （肝癖病）的中西医诊疗对策。
关键词代谢相关脂肪性肝病;肝癖病;脾痒；膏浊病；中西医诊疗对策中图分类号R575文献标志码AConsiderations and countermeasures for the treatment of metabolic associated fatty liver disease in Chinese and Western medicineZHANG Guo-hong,LI Xiao-don『0,ZH0U Ya-nc^'3,XIA0Ming-zhong19et al.1.Xujiapeng Branch,Hubei Provincial Hospital of Traditional Chinese Medicine(Wuhan Hubei,430061)China.Abstract In May2020,the international expert panel released the"Consensus on the Diagnosis and Management of Metabolic Associated Fatty Liver Disease(MAFLD)",proposing the use of the term*'MAFLD'1to replace the existing name"Non-Alcoholic Fatty Liver Disease(NAFLD)".The position statement further clarifies the clinical diagnosis and management guidelines for MAFLD.In this paper,we discuss the broad disease spectrum of MAFLD,the poor response to treatment,susceptibility genes and epigenetic factors,and the insufficient understanding of the disease by doctors and patients,as well as the Western diagnostic evaluation of MAFLD.We will discuss the Chinese and Western medicine treatment and countermeasures for MAFLD.Key Words:Metabolic associated fatty liver disease；fatty liver；Pi-dan；Gao Zhuo disease；treatment strategy2020年5月，国际专家小组发布了《代谢相关脂肪性肝病（MAFLD）的诊断和管理共识》，提出采用MAFLD 取代原有命名“非酒精性脂肪性肝病（NAFLD）”的立场声明⑷，共识确定了更适用于临床情境且简便的诊断评估标准，即提示在脂肪肝的基础上，只要合并超重/肥胖、2型糖尿病、代谢功能障碍等任一条件即可定义为MAFLD,并将血压、血脂、血糖受损、胰岛素抵抗和超敏C反应蛋白等纳入代谢功能障碍范围，进一步从临床实践出发，关注肝外合并的代谢相关问题。
苦荞醋饮的安全性初步研究张昕1，王晨尧1，司霞1，朱瑞芳1，2，曹妍3，冯耀清1，韩世范1，2*1.山西医科大学护理学院，山西 030001；2.山西医科大学第一医院；3.山西医学期刊社有限责任公司Preliminary study on safety of tartary buckwheat vinegar drinkZHANG Xin, WANG Chenyao, SI Xia, ZHU Ruifang, CAO Yan, FENG Yaoqing, HAN Shifan Nursing College of Shanxi Medical University, Shanxi 030001 ChinaCorresponding Author HANShifan,E⁃mail:*******************.cnAbstract Objective：To study whether buckwheat vinegar drink fermented from buckwheat for both medicine and food has acute oral toxicity and subacute oral toxicity，to provide animal test basis for safe food.Methods：In the acute oral toxicity test，the dose group was given 100 times of the recommended intake of the Tartary buckwheat vinegar drink by intragastric administration at a volume of 20 mL/kg，and the control group was given distilled water by gavage.The mice were observed for 14 days after gavage.To record the data on general observation，body weight changes，gross anatomical examination results，and organ coefficients data of the mice.In the 28⁃day oral toxicity test，the high，medium，and low dose groups were respectively given 100 times，50 times，25 times of the recommended intake of the Tartary buckwheat vinegar drink by intragastric administration at a volume of 10 mL/kg for 28 days continuously，and the control group was given distilled water by gavage.During the experiment，the general observation，body weight change，food intake，and food utilization rate of each group were recorded.At the end of the experiment，hematology examination，blood biochemical examination，gross anatomy examination，organ coefficient measurement，and histopathological examination were performed.Results：The mice did not appear symptoms of poisoning，and no pared with the control group，there was no significant difference in the body weights and organ coefficients of major organs of the mice in the dose group （P>0.05）.The rats did not appear symptoms of poisoning，and no death.The WBC of female rats in the low⁃dose group and the absolute weight of the spleen of male rats in the middle⁃dose group were significantly different from those in the control group （P<0.05）， but they were all within the normal range，so they had no clinical significance.There was no significant difference in other indicators compared with the control group （P>0.05）.Conclusion：This study proves that the Tartary buckwheat vinegar drink has no acute oral toxicity and subacute oral toxicity，and it is a safe and non⁃toxic food.Keywords tartary buckwheat vinegar drink； acute oral toxicity test； 28⁃day oral toxicity test； safety； medicinal and edible substance摘要目的:研究药食两用物质苦荞发酵而成的苦荞醋饮有无急性经口毒性和亚急性经口毒性，为安全的食品提供动物实验依据。
DOI：10.19368/ki.2096-1782.2023.14.055肝功能与血脂血清学指标水平检验在脂肪肝中的应用价值分析赵祥雷，江菊青，林立群南京市溧水区中医院/扬州大学医学院附属医院检验科，江苏南京211200 [摘要]目的研究分析肝功能与血脂血清学指标水平检验在脂肪肝中的应用价值。
方法选取2020年9月—2022年9月期间南京市溧水区中医院收治的脂肪肝患者80例设为研究组，按照脂肪肝严重程度分为轻度组（n=30）、中度组（n=30）、重度组（n=20），选取同期进行体检的健康者80例设为对照组。
对各组受检者的肝功能、血脂血清学指标进行检测与比较，分析肝功能与血脂血清学指标与脂肪肝严重程度的相关性。
结果研究组丙氨酸转氨酶水平（67.33±5.82）U/L、天冬氨酸转氨酶水平（66.49±5.88）U/L，高于对照组，差异有统计学意义（t=68.032、68.903，P<0.05）。
研究组总胆固醇、三酰甘油水平高于对照组，差异有统计学意义（P<0.05）。
重度组、中度组、轻度组丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、三酰甘油水平比较，差异有统计学意义（P<0.05）。
丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、三酰甘油水平与脂肪肝严重程度呈正相关（r=0.91、0.94、0.92、0.90，P<0.05）。
结论肝功能与血脂血清学指标水平检验在脂肪肝中的应用价值非常高，可在一定程度上反映患者病情严重程度，为其治疗提供了可靠的指导依据。
[关键词]脂肪肝；肝功能；血脂；血清学指标[中图分类号]R446 [文献标识码]A [文章编号]2096-1782（2023）07(b)-0055-04Analysis of the Application Value of Liver Function and Blood Lipid Sero⁃logical Index Level Testing in Fatty Liver DiseaseZHAO Xianglei, JIANG Juqing, LIN LiqunDepartment of Laboratory Medicine, Nanjing Lishui District Hospital of Traditional Chinese Medicine/Affiliated Hospi‐tal of Yangzhou University School of Medicine, Nanjing, Jiangsu Province, 211200 China[Abstract] Objective To study and analyze the application value of liver function and blood lipid serological index levels in fatty liver disease. Methods 80 patients with fatty liver admitted to the Hospital of Traditional Chinese Medi‐cine in Lishui District, Nanjing from September 2020 to September 2022 were selected as the research group. Accord‐ing to the severity of fatty liver, the patients were divided into mild group (n=30), moderate group (n=30), and severe group (n=20). 80 healthy subjects who underwent physical examination during the same period were selected as the control group. The liver function and blood lipid serological indicators of subjects in each group were detected and compared. The correlation between liver function and serum lipid index and the severity of fatty liver was analyzed.Results The levels of alanine aminotransferase ( 67.33±5.82 ) U/L and aspartate aminotransferase ( 66.49±5.88 )U/L in the study group were higher than those in the control group, and the difference was statistically significant (t= 68.032, 68.903, P<0.05 ). The levels of total cholesterol and triglyceride in the study group were higher than those in the control group, and the difference was statistically significant ( P<0.05 ). There was statistically significant differ‐ence in alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride levels among severe group, moderate group and mild group ( P<0.05 ). The levels of alanine aminotransferase, aspartate aminotransferase, [作者简介] 赵祥雷（1984-），男，本科，主管检验师，研究方向为检验生化。
∗基金项目:山东省中医药科研研究项目(编号:2020Q063)作者单位:261042山东省烟台市滨州医学院附属烟台医院检验科(蔡欣);血液内科(辛春红);肝胆胰脾外科(牛洪凯);烟台市中医医院检验科(兰春祥)第一作者:蔡欣,女,35岁,医学硕士,主管检验师㊂E-mail:li-uhuikk1977@通讯作者:兰春祥,E-mail:1256447326@ ㊃非酒精性脂肪性肝病㊃代谢相关脂肪性肝病患者血清HIF-1α、Chemerin和脂联素水平变化及临床意义探讨∗蔡欣,辛春红,牛洪凯,兰春祥㊀㊀ʌ摘要ɔ㊀目的㊀分析代谢相关脂肪性肝病(MAFLD)患者血清缺氧诱导因子-1α(HIF-1α)㊁Chemerin和脂联素(ADPN)水平变化及其临床意义㊂方法㊀2020年3月~2022年10月我院诊治的MAFLD患者86例和同期经年龄和性别匹配的健康体检者43例,应用超声检查评估肝脂肪变程度,采用ELISA法检测血清HIF-1α㊁Chemerin和ADPN水平,应用受试者工作特征曲线下面积(AUC)分析血清指标评估MAFLD患者肝重度脂肪变的效能㊂结果㊀MAFLD组血清HIF-1α和Chemerin水平分别为(16.6ʃ3.1)μg/L和(92.7ʃ8.9)μg/L,均显著高于对照组ʌ分别为(9.2ʃ2.1)μg/L和(60.4ʃ9.5)μg/L,均P<0.05ɔ,而血清ADPN水平为(15.1ʃ3.8)mg/L,显著低于对照组ʌ(25.4ʃ6.2)mg/L,P<0.05ɔ;35例重度脂肪变MAFLD患者血清HIF-1α和Chemerin水平分别为(19.9ʃ3.7)μg/L和(107.9ʃ10.5)μg/L,显著高于29例中度脂肪变患者ʌ分别为(16.3ʃ1.9)μg/L和(92.9ʃ8.7)μg/L,P<0.05ɔ或22例轻度脂肪变患者ʌ分别为(10.5ʃ1.8)μg/L和(84.0ʃ8.3)μg/L,P<0.05ɔ,而血清ADPN水平为(12.3ʃ2.8)mg/L,显著低于中度脂肪变患者ʌ(16.4ʃ4.8)mg/L,P<0.05ɔ或轻度脂肪变患者ʌ(24.2ʃ4.2)mg/L,P<0.05ɔ;多因素Logistic回归分析显示,空腹血糖㊁甘油三酯㊁总胆固醇㊁低密度脂蛋白胆固醇㊁HIF-1α和Chemerin高水平及ADPN低水平是MAFLD患者发生肝重度脂肪变的独立危险因素(P<0.05);联合应用血清HIF-1α㊁Chemerin和ADPN水平评估肝重度脂肪变的AUC为0.920,显著高于三项指标单一评估的0.846㊁0.742和0.795(P<0.05)㊂结论㊀MAFLD患者存在血清HIF-1α和Chemerin升高及ADPN水平下降,且三者变化与肝脂肪变程度相关,其临床意义值得进一步探究㊂㊀㊀ʌ关键词ɔ㊀代谢相关脂肪性肝病;缺氧诱导因子-1α;Chemerin;脂联素;诊断㊀㊀DOI:10.3969/j.issn.1672-5069.2023.05.013㊀㊀Changes of serum HIF-1α,Chemerin and adiponectin levels in patients with metabolic-associated fatty liver diseases㊀Cai Xin,Xin Chunhong,Niu Hongkai,et al.Clinical Laboratory,Yantai Hospital Affiliated to Binzhou Medical College,Yantai 261042,Shandong Province,China㊀㊀ʌAbstractɔ㊀Objective㊀The aim of this study was to explore the changes of serum hypoxia-inducible factor-1α(HIF-1α),chemerin and adiponectin(ADPN)levels in patients with metabolic-associated fatty liver diseases(MAFLD).Methods㊀86patients with MAFLD and43healthy individuals at physical healthy examination matched by age and gender were consecutively encountered in our hospital between March2020and October2022.Serum levels of HIF-1α,Chemerin and ADPN were detected by ELISA,and the hepatic steatosis was evaluated by ultrasonography.The area under the receiver operating characteristic curve (AUC)was applied to analyze the diagnostic performance of serum indicators on severe steatosis in patients with MAFLD.Results ㊀Serum HIF-1αand chemerin levels in patients with MAFLD were(16.6ʃ3.1)μg/L and(92.7ʃ8.9)μg/L,both significantly higher than[(9.2ʃ2.1)μg/L and(60.4ʃ9.5)μg/L,P<0.05]in the control,while serum ADPN level was(15.1ʃ3.8)mg/L, significantly lower than[(25.4ʃ6.2)mg/L,P<0.05]in the control;serum HIF-1αand chemerin levels in35patients with severe hepatic steatosis were(19.9ʃ3.7)μg/L and(107.9ʃ10.5)μg/L,both significantly higher than[(16.3ʃ1.9)μg/L and (92.9ʃ8.7)μg/L,P<0.05]in29patients with moderate liver steatosis or[(10.5ʃ1.8)μg/L and(84.0ʃ8.3)μg/L,P<0.05]in22patients with mild steatosis,while serum ADPNlevel was(12.3ʃ2.8)mg/L,much lower than[(16.4ʃ4.8)mg/L,P<0.05]in patients with moderate steatosis or[(24.2ʃ4.2)mg/L,P<0.05]in patients with mild steatosis;themultivariate Logistic regression analysis showed that the fastingblood glucose,triglyceride,total cholesterol,low-densitylipoprotein cholesterol,HIF-1αand chemerin and low level ofADPN were the independent risk factors for severe steatosis inpatients with MAFLD(P<0.05);the AUC was0.920by the combination of serum HIF-1α,chemerin and ADPN levels in predicting severe steatosis in patients with MAFLD,much larger than0.846,0.742and0.795(P<0.05)by the three parameter alone.Conclusion㊀Serum HIF-1αand chemerin levels increase,while serum ADPN level decrease in patients with MAFLD,and the changes of the above three parameters are related to the steatosis degree in patients with MAFLD,and their clinical implications are worthy of further investigation.㊀㊀ʌKey wordsɔ㊀Metabolic-associated fatty liver disease;Hypoxia-inducible factor-1α;Chemerin;Adiponectin;Diagnosis㊀㊀代谢相关脂肪性肝病(metabolic dysfunction as-sociated fatty liver diseases,MAFLD)既往被称为非酒精性脂肪性肝病(nonalcoholic fatty liver diseases, NAFLD),2020年亚太肝病学会将其更名为MAFLD,其疾病谱包括非酒精性脂肪肝㊁非酒精性脂肪性肝炎及其相关的肝纤维化和肝硬化等[1]㊂近年来,随着大众生活方式和饮食结构的改变,如久坐不动㊁高脂饮食等,糖尿病㊁肥胖及其代谢功能障碍人群增多,MAFLD患病率逐年升高,已成为全球范围内最常见的慢性肝病之一[2]㊂早诊断并及时采取有效防治措施是延缓MAFLD病情进展㊁改善患者预后的重要方法,但MAFLD发病机制尚未完全阐明,临床仍缺乏积极有效的治疗手段㊂因此,分析影响MAFLD 疾病进展的相关因素,探究治疗的新方向,已成为国内外学者研究的热点[3,4]㊂脂肪负荷过重使MAFLD 患者肝细胞肿胀,引起肝窦变形及微循环障碍,血流减慢,局部组织缺氧,而缺氧是脂肪组织功能障碍的关键因素,可诱导脂肪纤维化及肝脏脂肪代谢异常,加剧MAFLD进展㊂缺氧也是MAFLD发生㊁发展的风险因素[5]㊂缺氧诱导因子-1α(hypoxia inducible factor1α,HIF-1α)是细胞及组织缺氧标志㊂近年研究发现[6],HIF-1α可通过上调血管内皮生长因子和血管生成素-2表达,促进肝纤维化发展,诱导肝细胞癌变㊂脂联素(adiponectin,ADPN)为脂肪细胞特异性分泌蛋白,具有抗炎作用,还可增强肝脏对胰岛素的敏感性,延缓脂肪性肝炎进程,可能是MAFLD 疾病进展的保护因子[7]㊂另外,Chemerin是一种新发现的脂肪因子,与机体血脂㊁血压㊁胰岛素抵抗等均存在相关性,参与代谢功能障碍的发生㊂近年研究指出[8],Chemerin可能通过调节脂代谢㊁炎症和胰岛素等通路,参与MAFLD的发病过程㊂本研究检测了MAFLD患者血清HIF-1α㊁Chemerin和ADPN水平变化,现将结果报道如下㊂1㊀资料与方法1.1病例来源㊀2020年3月~2022年10月我院诊治的MAFLD患者86例,男性52例,女性34例;年龄为30~63岁,平均年龄为(38.6ʃ6.9)岁㊂符合2020年亚太肝病学会更新的MAFLD诊断标准[9]:基于血生化㊁影像学检查,同时符合⑴超重/肥胖;⑵Ⅱ型糖尿病;⑶代谢功能障碍㊂3项中任一项阳性,支持诊断㊂排除标准:⑴既往有肝脏㊁脾脏或胆道手术史;⑵合并病毒性肝炎;⑶合并自身免疫性㊁酒精性肝病或药物性肝损害;⑷合并甲状腺功能亢进或减退症㊁血液系统疾病㊁心肺功能不全㊁恶性肿瘤;⑸妊娠或哺乳期女性;⑹入组前1个月内应用过非甾体类抗炎药物㊂另选择同期经年龄和性别匹配的健康体检者43例作为对照组,男性26例,女性17例;年龄为30~62岁,平均年龄为(38.2ʃ6.5)岁㊂本研究获得我院医学伦理委员会审核㊁批准㊂1.2肝脏脂肪变程度判断㊀使用日本佳能Aplio i900彩色多普勒超声诊断仪(探头频率为1~8MHz)探测肝脏,参考‘非酒精性脂肪性肝病防治指南(2018年更新版)“[9]将肝脏脂肪变程度分为轻度(肝实质回声密集增强,肝内管道结构及膈肌清晰可见)㊁中度(肝脏形态饱满,近场回声增强,远场回声稍衰减,光点密集,肝内管道结构显示不清,膈肌回声中断)和重度(肝脏增大,近场回声明显增强,远场回声明显衰减,肝内管道结构和膈肌不可见)㊂1.3实验室指标检测㊀使用日本奥林巴斯株式会社提供的全自动生化分析仪检测空腹血糖(fasting plasma glucose,FPG)和其他血生化指标;采用ELISA 法检测血清HIF-1α㊁Chemerin和ADPN水平(武汉新启迪生物科技有限公司)㊂1.4统计学方法㊀应用R4.1.2软件进行统计学分析㊂对计量资料先行Shapiro-Wilk检验,判断是否服从正态分布㊂对符合正态分布者,以(xʃs)表示,采用t检验㊂应用Logistic回归分析影响MAFLD患者发生重度肝脂肪变的危险因素,并建立受试者工作特征(receiver operating characteristic,ROC)曲线,以曲线下面积(areas under curve,AUC)分析血清指标评估MAFLD患者重度肝脂肪变的效能㊂可信区间为95%,所有检验均为双侧检验,P<0.05为差异有统计学意义㊂2㊀结果2.1两组血糖和血脂水平比较㊀MAFLD组FPG㊁血清TG㊁TC和LDL-C水平显著高于对照组(P<0.05,表1)㊂表1㊀两组血糖和血脂水平(x ʃs )比较例数FPG(mmol /L)TG(mmol /L)TC(mmol /L)LDL -C(mmol /L)HDL -C(mmol /L)MAFLD 86 5.8ʃ0.9① 2.9ʃ0.4① 5.6ʃ0.8① 3.4ʃ0.6① 1.1ʃ0.3对照组435.0ʃ0.81.6ʃ0.34.3ʃ0.82.7ʃ0.51.2ʃ0.3㊀㊀与对照组比,①P <0.052.2两组血清HIF -1α㊁Chemerin 和ADPN 水平比较㊀MAFLD 组血清HIF -1α和Chemerin 水平显著高于对照组,而血清ADPN 水平显著低于对照组(P <0.05,表2)㊂表2㊀两组血清HIF -1α㊁Chemerin 和ADPN 水平(x ʃs )比较例数HIF -1α(μg /L)Chemerin (μg /L)ADPN(mg /L)MAFLD 8616.6ʃ3.1①92.7ʃ8.9①15.1ʃ3.8①对照组439.2ʃ2.160.4ʃ9.525.4ʃ6.2㊀㊀与对照组比,①P <0.052.3不同肝脂肪变的MAFLD 患者血清HIF -1α㊁Chemerin 和ADPN 水平比较㊀重度肝脂肪变的MAFLD 患者血清HIF -1α和Chemerin 水平显著高于中度或轻度脂肪变患者,而血清ADPN 水平显著低于中度肝脂肪变或轻度肝脂肪变患者(P <0.05,表3)㊂表3㊀不同脂肪变患者血清HIF -1α㊁Chemerin和ADPN 水平(x ʃs )比较肝脂肪变例数HIF -1α(μg /L)Chemerin (μg /L)ADPN(mg /L)轻度2210.5ʃ1.884.0ʃ8.324.2ʃ4.2中度2916.3ʃ3.9①92.9ʃ8.7①16.4ʃ4.8①重度3519.9ʃ3.7①②107.9ʃ10.5①②12.3ʃ2.8①②㊀㊀与轻度组比,①P <0.05;与中度组比,②P <0.052.4影响MAFLD 患者肝脂肪变程度的多因素Logistic 回归分析㊀经Logistic 回归分析显示,血清FPG㊁TG㊁TC㊁LDL -C㊁HIF -1α和Chemerin 高水平及血清ADPN 低水平是影响MAFLD 患者肝重度脂肪变的独立危险因素(P <0.05,表4)㊂表4㊀影响MAFLD 患者肝脂肪变程度的Logistic 回归分析β值SE 值Wald x 2值OR 值95%CI P FPG 0.8210.2967.693 2.273 1.105~4.6760.006TG 0.7660.2777.647 2.151 1.033~4.4780.006TC 0.6390.267 5.728 1.895 1.012~4.4010.017LDL -C0.6120.259 5.583 1.844 1.009~4.3470.018HIF -1α0.8050.2758.569 2.237 1.118~4.4740.018Chemerin0.7530.2817.181 2.123 1.024~4.5110.007ADPN-0.8060.2897.7780.4470.155~0.8400.0052.5血清HIF -1α㊁Chemerin 和ADPN 评估MAFLD 患者肝重度脂肪变的效能情况㊀经ROC 曲线分析显示,联合应用血清HIF -1α㊁Chemerin 和ADPN 水平评估MAFLD 患者肝重度脂肪变的AUC 显著大于三项指标单一评估(P <0.05),其评估效能最高(表5㊁图1)㊂表5㊀血清HIF -1α㊁Chemerin 和ADPN 评估MAFLD 患者肝重度脂肪变的效能截断点AUC 95%CI 敏感度(%)特异度(%)P 值HIF -1α17.7μg /L 0.8460.754~0.93880.080.4<0.001Chemerin 93.0μg /L0.7420.632~0.85374.366.7<0.001ADPN15.8mg /L0.7950.703~0.88788.664.7<0.0013项联合-0.9200.862~0.97894.362.7<0.001图1㊀血清HIF -1α㊁Chemerin 和ADPN 评估MAFLD 患者肝重度脂肪变的效能3㊀讨论目前,MAFLD 发病机制尚在探索阶段,但普遍认为其主要与脂代谢紊乱㊁胰岛素抵抗和氧化应激反应有关[10]㊂MAFLD 患者胰岛素敏感性显著降低,导致其对糖脂代谢的调节作用减弱,造成血糖及血脂水平异常,而这种改变越明显,肝脏脂肪沉积就越重,肝损伤也进一步加剧[11]㊂Chemerin 作为本世纪初期发现的脂肪因子,与肥胖和代谢综合征发生机制密切相关,可募集单核细胞源性巨噬细胞和浆细胞样树突状细胞聚集于炎症反应部位,调控局部炎症反应[12]㊂近年来有报道称[13],Chemerin可通过蛋白激酶B磷酸化及磷酸腺苷活化激酶活化,影响胰岛素敏感性,且能募集中性粒细胞和淋巴细胞聚集于肝内,加剧肝组织炎症反应,而作为胰岛素敏感性调节因子和炎症反应介质,参与MAFLD的发生和发展㊂Chemerin与疾病发生机制的相关报道主要集中在肥胖和代谢综合征[14],其是否通过影响胰岛素敏感性及肝内炎症反应,调控MAFLD的发生㊂健康人群血浆含有丰富的ADPN,而在代谢综合征㊁肥胖和糖尿病人群ADPN水平显著下降[15]㊂MAFLD患者肝组织和血浆ADPN水平均显著下降㊂ADPN可通过影响肝组织炎症反应,参与MAFLD的发生[16]㊂在慢性乙型肝炎合并MAFLD患者,肝脂肪变越严重者血清ADPN水平越低[17]㊂肝脂肪变不仅可引起肝细胞处于缺氧状态,脂肪沉积于肝组织也可导致肝脏对缺血缺氧的耐受性下降,更易发生肝损伤㊂据文献报道[18],MAFLD患者肝细胞处于缺氧状态,可诱导HIF-1α上调,激活转化生长因子β1和血管内皮生长因子信号通路,诱导血管新生,加速病情进展[19]㊂在小鼠模型实验发现,酒精性脂肪性肝病肝组织HIF-1α表达也显著上调,并通过调节炎症反应及氧化应激水平,参与肝损伤的发生㊂研究发现[20,21],缺氧诱导HIF-1α激活,使核因子κB亚基向核转运,诱导一系列炎症因子的分泌和释放,增强炎症反应㊂ʌ参考文献ɔ[1]Eslam M,Sanyal AJ,George J,et al.MAFLD:A consensus-driven proposed nomenclature for metabolic associated fatty liver dis-ease.Gastroenterology,2020,158(7):1999-2014. 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