血清学诊断非酒精性脂肪性肝病的研究进展

郭滔; 胡波; 易为民; 钟振东; 刘苏来; 孙增鹏; 彭创

doi:10.3969/j.issn.1001-5256.2020.11.041

血清学诊断非酒精性脂肪性肝病的研究进展

DOI: 10.3969/j.issn.1001-5256.2020.11.041

湖南师范大学附属第一医院湖南省人民医院肝胆外科

基金项目:

湖南省自然科学基金（2019JJ50320）；湖南省卫生厅科研基金（20200179）；

详细信息

中图分类号: R575.5
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出版历程
- 收稿日期: 2020-05-05
- 出版日期: 2020-11-20

Research advances in the serological diagnosis of nonalcoholic fatty liver disease

Department of Hepatobiliary Surgery,Hunan Provincial People's Hospital & The First Affiliated Hospital of Hunan Normal University

Research funding:

摘要

摘要:
近年来非酒精性脂肪性肝病（NAFLD）的患病率明显升高,已逐渐成为我国常见的慢性肝病之一。而NAFLD相关终末期或恶化性肝病患者已成为肝移植的主要人群之一。NAFLD发病率的增加和非酒精性脂肪性肝炎（NASH）的严重后果使得有必要使用有效的方法来识别NAFLD。基于此,总结了目前血清学方法诊断NAFLD,包括脂肪变性、NASH和肝纤维化,并探讨了其优缺点。尽管大部分血清标志物真正应用于临床的价值有限,但血清标志物模型在诊断肝脂肪变性及评估纤维化程度和初步筛查方面均有较好的应用前景。由于联合不同血清学模型可以提高诊断的准确度,因此开展多角度、多中心的联合诊断将是未来的研究热点。
- 非酒精性脂肪性肝病 /
- 诊断 /
- 生物标记
Abstract:
In recent years,the prevalence rate of nonalcoholic fatty liver disease( NAFLD) has increased significantly and NAFLD has gradually become one of the common chronic liver diseases in China. Patients with NAFLD-related end-stage or deteriorative liver diseases have become one of the main populations for liver transplantation. The increasing prevalence rate of NAFLD and the severe outcomes of nonalcoholic steatohepatitis( NASH) make it necessary to use effective methods to identify NAFLD. Therefore,this article summarizes the current serological methods for the diagnosis of NAFLD,including steatosis,NASH,and liver fibrosis,and discusses their advantages and disadvantages. Although most of the serum markers have limited clinical value,serum marker models have a good application prospect in the diagnosis of hepatic steatosis,the evaluation of fibrosis degree,and preliminary screening. Since a combination of different serological models can improve the accuracy of diagnosis,multi-angle and multicenter joint diagnosis will be a research hotspot in the future.
- nonalcoholic fatty liver disease /
- diagnosis /
- biomarkers

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参考文献(44)

[1]YOUNOSSI ZM,KOENIG AB,ABDELATIF D,et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.

[2]KIM GA,LEE HC,CHOE J,et al.Association between nonalcoholic fatty liver disease and cancer incidence rate[J].J Hepatol,2017.[Online ahead of print]

[3]STARLEY BQ,CALCAGNO CJ,HARRISON SA.Nonalcoholic fatty liver disease and hepatocellular carcinoma:A weighty connection[J].Hepatology,2010,51(5):1820-1832.

[4]VERNON G,BARANOVA A,YOUNOSSI ZM.Systematic review:The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults[J].Aliment Pharmacol Ther,2011,34(3):274-285.

[5]BEDOGNI G,BELLENTANI S,MIGLIOLI L,et al.The Fatty LiverIndex:A simple and accurate predictor of hepatic steatosis in the general population[J].BMC Gastroenterol,2006,6:33.

[6]KOTRONEN A,PELTONEN M,HAKKARAINEN A,et al.Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors[J].Gastroenterology,2009,137(3):865-872.

[7]KOOT BG,van der BAAN-SLOOTWEG OH,BOHTE AE,et al.Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children[J].Obesity(Silver Spring),2013,21(3):583-590.

[8]WANG J,XU C,XUN Y,et al.ZJU index:A novel model for predicting nonalcoholic fatty liver disease in a Chinese population[J].Sci Rep,2015,5:16494.

[9]LI L,YOU W,REN W.The ZJU index is a powerful index for identifying NAFLD in the general Chinese population[J].Acta Diabetol,2017,54(10):905-911.

[10]POYNARD T,RATZIU V,NAVEAU S,et al.The diagnostic value of biomarkers(SteatoTest)for the prediction of liver steatosis[J].Comp Hepatol,2005,4:10.

[11]HE L,DENG L,ZHANG Q,et al.Diagnostic value of CK-18,FGF-21,and related biomarker panel in nonalcoholic fatty liver disease:A systematic review and Meta-analysis[J].Biomed Res Int,2017,2017:9729107.

[12]ANTY R,IANNELLI A,PATOURAUX S,et al.A new composite model including metabolic syndrome,alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients[J].Aliment Pharmacol Ther,2010,32(11-12):1315-1322.

[13]GRIGORESCU M,CRISAN D,RADU C,et al.A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis[J].J Physiol Pharmacol,2012,63(4):347-353.

[14]ALKHOURI N,ALISI A,OKWU V,et al.Circulating soluble fasand fas ligand levels are elevated in children with nonalcoholic steatohepatitis[J].Dig Dis Sci,2015,60(8):2353-2359.

[15]QI S,XU D,LI Q,et al.Metabonomics screening of serum identifies pyroglutamate as a diagnostic biomarker for nonalcoholic steatohepatitis[J].Clin Chim Acta,2017,473:89-95.

[16]UCHIHARA M,IZUMI N.High-sensitivity C-reactive protein(hs-CRP):A promising biomarker for the screening of nonalcoholic steatohepatitis(NASH)[J].Nihon Rinsho,2006,64(6):1133-1138.

[17]BOGA S,KOKSAL AR,ALKIM H,et al.Plasma pentraxin 3 differentiates nonalcoholic steatohepatitis(NASH)from non-NASH[J].Metab Syndr Relat Disord,2015,13(9):393-399.

[18]ZHANG X,SHEN J,MAN K,et al.CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis[J].J Hepatol,2014,61(6):1365-1375.

[19]SHEN J,CHAN HL,WONG GL,et al.Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers[J].J Hepatol,2012,56(6):1363-1370.

[20]TIETGE UJ,SCHMIDT HH,SCHUTZ T,et al.Reduced plasma adiponectin in NASH:Central obesity as an underestimated causative risk factor[J].Hepatology,2005,41(2):401;author reply 401-402.

[21] YONEDA M,NOZAKI Y,ENDO H,et al.Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis(NASH)independent of HFE gene mutation[J].Dig Dis Sci,2010,55(3):808-814.

[22]KOWDLEY KV,BELT P,WILSON LA,et al.Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease[J].Hepatology,2012,55(1):77-85.

[23]OKANOUE T,EBISE H,KAI T,et al.A simple scoring system using type IV collagen 7S and aspartate aminotransferase for diagnosing nonalcoholic steatohepatitis and related fibrosis[J].J Gastroenterol,2018,53(1):129-139.

[24]LIU CH,AMPUERO J,GIL-GOMEZ A,et al.miRNAs in patients with non-alcoholic fatty liver disease:A systematic review and meta-analysis[J].J Hepatol,2018,69(6):1335-1348.

[25]PIROLA CJ,FERNANDEZ GIANOTTI T,CASTANO GO,et al.Circulating microRNA signature in non-alcoholic fatty liver disease:From serum non-coding RNAs to liver histology and disease pathogenesis[J].Gut,2015,64(5):800-812.

[26]BECKER PP,RAU M,SCHMITT J,et al.Performance of serum microRNAs-122,-192 and-21 as biomarkers in patients with non-alcoholic steatohepatitis[J].PLoS One,2015,10(11):e0142661.

[27]YOUNOSSI ZM,LOOMBA R,ANSTEE QM,et al.Diagnostic modalities for non-alcoholic fatty liver disease(NAFLD),non-alcoholic steatohepatitis(NASH)and associated fibrosis[J].Hepatology,2017,68(1):349-360.

[28]POYNARD T,RATZIU V,CHARLOTTE F,et al.Diagnostic value of biochemical markers(NashTest)for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease[J].BMC Gastroenterol,2006,6:34.

[29]ZHOU Y,ORESIC M,LEIVONEN M,et al.Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites[J].Clin Gastroenterol Hepatol,2016,14(10):1463-1472.e6.

[30]HANSEN JF,JUUL NIELSEN M,NYSTROM K,et al.PROC3:A new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C[J].Scand J Gastroenterol,2018,53(1):83-87.

[31] DANIELS SJ,LEEMING DJ,ESLAM M,et al.ADAPT:An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis[J].Hepatology,2019,69(3):1075-1086.

[32]CHERNBUMROONG S,GROVE JI,ASTBURY S,et al.Advanced machine learning techniques to identify a panel of biomarkers that identify nonalcoholic steatohepatitis[J].Hepatol-ogy,2017,66(S1):53A-54A.

[33]POLYZOS SA,SLAVAKIS A,KOUMERKERIDIS G,et al.Noninvasive liver fibrosis tests in patients with nonalcoholic fatty liver disease:An external validation cohort[J].Horm Metab Res,2019,51(2):134-140.

[34]TANWAR S,TREMBLING PM,GUHA IN,et al.Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease[J].Hepatology,2013,57(1):103-111.

[35]SUZUKI A,ANGULO P,LYMP J,et al.Hyaluronic acid,an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease[J].Liver Int,2005,25(4):779-786.

[36]ABDELAZIZ R,ELBASEL M,ESMAT S,et al.Tissue inhibitors of metalloproteinase-1 and 2 and obesity related non-alcoholic fatty liver disease:Is there a relationship[J].Digestion,2015,92(3):130-137.

[37]LICHTINGHAGEN R,PIETSCH D,BANTEL H,et al.The Enhanced Liver Fibrosis(ELF)score:Normal values,influence factors and proposed cut-off values[J].J Hepatol,2013,59(2):236-242.

[38]XIAO G,ZHU S,XIAO X,et al.Comparison of laboratory tests,ultrasound,or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease:A meta-analysis[J].Hepatology,2017,66(5):1486-1501.

[39]European Association for Study of Liver,Asociacion Latinoamericana para el Estudio del Higado.EASL-ALEH clinical practice guidelines:Non-invasive tests for evaluation of liver disease severity and prognosis[J].J Hepatol,2015,63(1):237-264.

[40]ADAMS LA,GEORGEJ,BUGIANESI E,et al.Complex noninvasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease[J].J Gastroenterol Hepatol,2011,26(10):1536-1543.

[41]RATZIU V,MASSARD J,CHARLOTTE F,et al.Diagnostic value of biochemical markers(FibroTest-FibroSURE)for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease[J].BMC Gastroenterol,2006,6:6.

[42]ZHANG YL,MA YJ,WANG ZL,et al.Evaluation of four scoring systems in diagnosis of hepatic fibrosis in patients with nonalcoholic fatty liver disease[J].Chin J Modern Med,2017,27(22):112-126.(in Chinese)张意兰,马英杰,王志凌,等.4种评分系统在非酒精性脂肪肝病肝纤维化程度的诊断效能评价[J].中国现代医学杂志,2017,27(22):112-126.

[43]GUO ZQ,WANG QY,QI XS,et al.Recommendations for the diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases(2017)[J].J Clin Hepatol,2017,33(12):2275-2277.(in Chinese)郭泽淇,王倩怡,祁兴顺,等.《2017年美国肝病学会非酒精性脂肪性肝病诊疗指导》摘译[J].临床肝胆病杂志,2017,33(12):2275-2277.

[44]National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association;Fatty Liver Expert Committee,Chinese Medical Doctor Association.Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 update[J].J Clin Hepatol,2018,34(5):947-957.(in Chinese)中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南(2018年更新版)[J].临床肝胆病杂志,2018,34(5):947-957.

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