血清学指标在非酒精性脂肪性肝病诊断中的意义

万艳; 常剑波; 白艳霞; 李倩楠; 戴光荣

doi:10.3969/j.issn.1001-5256.2017.05.037

血清学指标在非酒精性脂肪性肝病诊断中的意义

DOI: 10.3969/j.issn.1001-5256.2017.05.037

延安大学附属医院

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中图分类号: R575.5
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出版历程
- 收稿日期: 2016-11-24
- 出版日期: 2017-05-20

Significance of serological markers in diagnosis of nonalcoholic fatty liver disease

Yan'an University Affiliated Hospital

摘要

摘要: 近年来,脂肪性肝病发病率呈明显上升趋势,肝脏活组织检查是诊断脂肪肝的金标准,但有其不可避免的缺点。目前尚缺乏一种方便、价廉、准确、适用于临床的无创诊断方法。主要回顾了多项血清学指标在非酒精性脂肪性肝病（NAFLD）诊断中的意义,认为血清学指标中肝酶、AST与ALT比值、血清铁蛋白、血清硒、尿酸、高空腹胰岛素浓度、视黄醇结合蛋白4、细胞角蛋白18、PNPLA3基因、TM6SF2基因在NAFLD的诊断中有较大的价值,而IL-28B对NAFLD的诊断价值存在较大争议,尚需更多临床试验证实。相信在不久的将来,多项血清指标组合会成为较准确,且适用于临床的早期诊断NAFLD、肝脂肪变性程度及肝纤维化程度的无创方法。
- 脂肪肝 /
- 生物学标记 /
- 诊断 /
- 综述
Abstract: In recent years, the incidence rate of fatty liver tends to increase markedly, and liver biopsy is the gold standard for the diagnosis of fatty liver, but it has some inevitable shortcomings.At present, there lacks a convenient, cheap, and accurate noninvasive diagnostic method for clinical practice.This article reviews the significance of various serological markers in the diagnosis of nonalcoholic fatty liver disease (NAFLD) and points out that liver enzyme, aspartate aminotransferase/alanine aminotransferase ratio, serum ferritin, serum selenium, uric acid, high fasting insulin level, retinol-binding protein-4, cytokeratin-18, PNPLA3 gene, and TM6SF2 gene have great significance in the diagnosis of NAFLD.There are still controversies over the value of interleukin-28 B in the diagnosis of NAFLD, and more clinical trials are needed.We believe that in the near future, a combination of various serum markers may become an accurate noninvasive method for the diagnosis of NAFLD and the assessment of the degree of liver fatty degeneration and fibrosis.
- fatty liver /
- biological markers /
- diagnosis /
- review

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参考文献(61)

[1]HAAS JT, FRANCQUE S, STAELS B.Pathophysiology and mechanisms of nonalcoholic fatty liver disease[J].Annu Rev Physiol, 2016, 78 (1) :181-205.

[2]NELSON JE, HANDA P, AOUIZERAT B, et al.Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms[J].Aliment Pharmacol Ther, 2016, 44 (11-12) :1253-1264.

[3]WU XM.Detection of fatty liver disease in people undergoing physical examination and related factors:an analysis of 867 cases[J].Jilin Med J, 2012, 33 (6) :1154-1155. (in Chinese) 吴晓铭.867例健康体检中脂肪肝检验结果与相关因素分析[J].吉林医学, 2012, 33 (6) :1154-1155.

[4]ARMSTRONG MJ, HOULIHAN DD, BENTHAM L, et al.Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort[J].J Hepatol, 2012, 56 (1) :234-240.

[5]CHEN Z, HAN CK, PAN LL, et al.Serum alanine aminotransferase independently correlates with intrahepatic triglyceride contents in obese subjects[J].Dig Dis Sci, 2014, 59 (10) :2470-2476.

[6]MAXIMOS M, BRIL F, SANCHEZ PP, et al.The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease[J].Hepatology, 2015, 61 (1) :153-160.

[7]CRUZ MA, CRUZ JF, MACENA LB, et al.Association of the nonalcoholic hepatic steatosis and its degrees with the values of liver enzymes and homeostasis model assessment-insulin resistance index[J].Gastroenterology Res, 2015, 8 (5) :260-264.

[8]BEDOGNI G, BELLENTANI S, MIGLIOLI L, et al.The fatty liver index:a simple and accurate predictor of hepatic steatosis in the generalpopulation[J].BMC Gastroenterol, 2006, 6 (2) :33-38.

[9]CHAN W K, IDA N H, CHEAH P L, et al.Progression of liver disease in non-alcoholic fatty liver disease:a prospective clinicopathological follow-up study[J].J Dige Dis, 2014, 15 (10) :545-552.

[10]KAWAMURA Y, IKEDA K, ARASE Y, et al.New discriminant score to predict the fibrotic stage of non-alcoholic steatohepatitis in Japan[J].Hepatol Int, 2015, 9 (2) :269-277.

[11]LEE JH, KIM D, KIM HJ, et al.Hepatic steatosis index:a simple screening tool reflecting nonalcoholic fatty liver disease[J].Dig Liver Dis, 2010, 42 (7) :503-508.

[12]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.

[13]RUFFILLO G, FASSIO E, ALVAREZ E, et al.Comparison of NAFLD fibrosis score and BARD score in predicting fibrosis in nonalcoholic fatty liver disease[J].J Hepatol, 2011, 54 (1) :160-163.

[14]FALLATAH HI, AKBAR HO, FALLATAH AM, et al.Fibroscan compared to FIB-4, APRI, and AST/ALT ratio for assessment of liver fibrosis in saudi patients with nonalcoholic fatty liver disease[J].Hepat Monm, 2016, 16 (7) :e38346.

[15]MANOUSOU P, KALAMBOKIS G, GRILLO F, et al.Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients[J].Liver Int, 2011, 31 (5) :730-739.

[16]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.

[17]MA HM, BAI PP, ZHANG LZ, et al.Change in serum ferritin level and its significance in patients with non-alcoholic fatty liver disease[J].Shandong Med J, 2016, 52 (29) :42-44. (in Chinese) 马会民, 白萍萍, 张连仲, 等.非酒精性脂肪肝患者血清铁蛋白水平变化及意义[J].山东医药, 2016, 52 (29) :42-44.

[18]FENG HP, REN YL.Signiifcance of serum ferritin in patients with non-alcoholic fatty liver disease[J/CD].Chin J Liver Dis:Electronic Edition, 2016, 8 (2) :113-115. (in Chinese) 冯红萍, 任艳玲.非酒精性脂肪性肝病患者血清铁蛋白检测的意义[J/CD].中国肝脏病杂志:电子版, 2016, 8 (2) :113-115.

[19]GOH GB, ISSA D, LOPEZ R, et al.The development of a non-invasive model to predict the presence of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease[J].J Gastroenterol Hepatol, 2016, 31 (5) :995-1000.

[20]HASEGAWA T, TANIGUCHI S, MIHARA M, et al.Toxicity and chemical form of selenium in the liver of mice orally administered selenocystine for 90 days[J].Arch Toxicol, 1994, 68 (2) :91-95.

[21]KOODZIEJCZYK L, PUT A, GRZELA P, et al.Liver morphology and histochemistry in rats resulting from ingestion of sodium selenite and sodium fluoride[J].Fluoride, 2000, 33:6-16.

[22]MUELLER AS, KLOMANN SD, WOLF NM, et al.Redox regulation of protein tyrosine phosphatase 1B by manipulation of dietary selenium affects the triglyceride concentration in rat liver[J].J Nutr, 2008, 138 (12) :2328-2336.

[23]STRANGES S, NAVAS-ACIEN A, RAYMAN MP, et al.Selenium status and cardiometabolic health:state of the evidence[J].Nutr Metab Cardiovasc Dis, 2010, 20 (10) :754-760.

[24]YANG Z, YAN C, LIU G, et al.Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults:a cross-sectional analysis[J].Sci Rep, 2016, 6:37288.

[25]SIROTA J C, MCFANN K, TARGHER G, et al.Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States:liver ultrasound data from the National Health and Nutrition Examination Survey[J].Metabolism, 2013, 62 (3) :215-216.

[26]YUAN H, YU C, LI X, et al.Serum uric acid levels and risk of metabolic syndrome:a dose-response meta-analysis of prospective studies[J].J Clin Endocrinol Metab, 2015, 100 (11) :4198-4207.

[27]LI SF, LIAO XH, YE JZ, et al.Role of uric acid in the development and progression of nonalcoholic fatty liver disease[J].J Clin Hepatol, 2016, 32 (9) :1814-1818. (in Chinese) 李韶丰, 廖献花, 叶俊钊, 等.尿酸在非酒精性脂肪性肝病发生发展中的作用[J].临床肝胆病杂志, 2016, 32 (9) :1814-1818.

[28]ZELBERSAGI S, BENASSULI O, RABINOWICH L, et al.The association between serum levels of uric-acid and alanine aminotransferase in a population-based cohort[J].Liver Int, 2015, 35 (11) :s750-s751.

[29]MASUDA K, NOGUCHI S, ONO M, et al.High fasting insulin concentrations may be a pivotal predictor for the severity of hepatic fibrosis beyond the glycemic status in nonalcoholic fatty liver disease patients before development of diabetes mellitus[J].Hepatol Res, 2016.[Epub ahead of print]

[30]GRAHAM TE, YANG Q, BLUHER M, et al.Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects[J].N Engl J Med, 2006, 354 (24) :2552-2563.

[31]SUN LS, FAN LY, WANG N, et al.The correlation between serum RBP-4 and nonalcoholic fatty liver disease[J].Lab Med, 2011, 26 (9) :602-605. (in Chinese) 孙立山, 范列英, 王暖, 等.血清视黄醇结合蛋白4和非酒精性脂肪性肝病的相关性[J].检验医学, 2011, 26 (9) :602-605.

[32]CHANG X, YAN H, BIAN H, et al.Serum retinol binding protein4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes:a cross-sectional study[J].Lipids Health Dis, 2015, 14:28.

[33]LIU Y, MU D, CHEN H, et al.Retinol-binding protein 4 induces hepatic mitochondrial dysfunction and promotes hepatic steatosis[J].J Clin Endocrinol Metab, 2016, 101 (11) :4338-4348.

[34]MALIKEN BD, NELSON JE, KLINTWORTH HM, et al.Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease[J].Hepatology, 2013, 57 (5) :1806-1813.

[35]CASTERA L, VILGRAIN V, ANGULO P.Noninvasive evaluation of NAFLD[J].Nat Rev Gastroenterol Hepatol, 2013, 10 (11) :666-675.

[36]CHALASANI N, YOUNOSSI Z, LAVINE JE, et al.The diagnosis and management of non-alcoholic fatty liver disease:practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology[J].Gastroenterology, 2012, 142 (7) :15921-609.

[37]KAZANKOV K, BARRERA F, MØLLER HJ, et al.The macrophage activation marker s CD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease[J].Liver Int, 2016, 36 (10) :1549-1557.

[38]FELDSTEIN AE, ALKHOURI N, DE VR, et al.Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children[J].Am J Gastroenterol, 2013, 108 (9) :1526-1531.

[39]LI N, ZHOU MJ, CHEN N.Expression and significance of serum TNF-αand CK-18 levels in children with non-alcoholic steatohepatitis[J].Chin Gen Pract, 2014, 17 (15) :1723-1727. (in Chinese) 李娜, 周明锦, 陈楠.非酒精性脂肪性肝炎患儿血清肿瘤坏死因子α与细胞角质蛋白18的表达及意义研究[J].中国全科医学, 2014, 17 (15) :1723-1727.

[40]ZWOLAK A, SZUSTER-CIESIELSKA A, DANILUK J, et al.Chemerin, retinol binding protein-4, cytokeratin-18 and transgelin-2 presence in sera of patients with non-alcoholic liver fatty disease[J].Ann Hepatol, 2016, 15 (6) :862-869.

[41]KADOWAKI T, YAMAUCHI T.Adiponectin and adiponectin receptors.[J].Endocrine Reviews, 2005, 26 (3) :439-451.

[42]POLYZOS SA, TOULIS KA, GOULIS DG, et al.Serum total adiponectin in nonalcoholic fatty liver disease:a systematic review and meta-analysis[J].Metabolism, 2011, 60 (3) :313-326.

[43]LAN CM.Measurements of tumor necrosis factor-αand interleukin-6 and their significance in patients with varying degrees of nonalcoholic fatty liver disease[J].Mod Digest Interv, 2016, 21 (1) :85-87. (in Chinese) 蓝常明.不同程度非酒精性脂肪肝患者肿瘤坏死因子-α、白介素-6的检测及意义[J].现代消化及介入诊疗, 2016, 21 (1) :85-87.

[44]SEVERSON TJ, BESUR S, BONKOVSKY HL.Genetic factors that affec nonalcoholic fatty liver disease:a systematic clinical review.[J].World JGastroenterol, 2016, 22 (29) :6742-6756.

[45]KRAWCZYK M, RAU M, SCHATTENBERG JM, et al.Combined effects of the TM6SF2 rs58542926, PNPLA3 rs738409 and MBOAT7 rs641738 variants on NAFLD severity:multicentre biopsy-based study[J].J Lipid Res, 2017, 58 (1) :247-255.

[46]SEKO Y, SUMIDA Y, TANAKA S, et al.Development of hepatocellular carcinoma in Japanese patients with biopsy-proven non-alcoholic fatty liver disease:association between PNPLA3 genotype and hepatocarcinogenesis/fibrosis progression[J].Hepatol Res, 2016.[Epub ahead of print]

[47]KOZLITINA J, SMAGRIS E, STENDER S, et al.Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease[J].Nat Genet, 2014, 46 (4) :352-356.

[48]WANG X, LIU Z, WANG K, et al.Additive effects of the risk alleles of PNPLA3 and TM6SF2 on non-alcoholic fatty liver disease (NAFLD) in a Chinese population[J].Front Genet, 2016, 7:140.

[49]KRAWCZYK M, RAU M, SCHATTENBERG J, et al.Combined effects of the prosteatotic TM6SF2 and PNPLA3 variants on severity o NALFD:multicentre biopsy-based study in German patients[J].ZGastroenterol, 2015, 53 (12) :1391-1602.

[50]CAI T, DUFOUR JF, MUELLHAUPT B, et al.Viral genotypespecifi c role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis[J].J Hepatol, 2011, 55 (3) :529-535.

[51]ABE H, OCHI H, MAEKAWA T, et al.Common variation of IL28affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients[J].J Hepatol, 2010, 53 (3) :439-443.

[52]MARABITA F, AGHEMO A, de NICOLA S, et al.Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection[J].Hepatology, 2011, 54 (4) :1127-1134.

[53]PETTA S, GRIMAUDO S, CAMMA C, et al.IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease[J].J Hepatol, 2012, 56 (6) :1356-1362.

[54]PETTA S, CRAXI A.Reply to:“IL28B rs12979860 is not associated with histologic features of NAFLD in a cohort of Caucasian North American patients”[J].J Hepatol, 2013, 58 (2) :403-404.

[55]GARRETT ME, ABDELMALEK MF, ASHLEY-KOCH A, et al.IL28B rs12979860 is not associated with histologic features of NAFLDin a cohort of Caucasian North American patients[J].J Hepatol, 2013, 58 (2) :402-403.

[56]HASHEMI M, MOAZENI-ROODI A, BAHARI A, et al.A tetra-primer amplification refractory mutation system-polymerase chain reaction for the detection of rs8099917 IL28B genotype[J].Nucleosides Nucleotides Nucleic Acids, 2012, 31 (1) :55-60.

[57]LI JW.Association between polymorphisms of rs12979860 and rs8099917 in IL28B gene and non-alcoholic fatty liver disease[D].Dalian:Dalian Med Univ, 2015. (in Chinese) 李江文.IL28B基因rs12979860、rs8099917多态性与NAFLD的相关性研究[D].大连:大连医科大学, 2015.

[58]POYNARD T, RATZIU V, NAVEAU S, et al.The diagnostic value of bio-markers (Steato Test) for the prediction of liver steatosis[J].Comp Hepatol, 2005, 4 (23) :10-17.

[59]BEDOGNI G, KAHN HS, BELLENTANI S, et al.A simple index of lipidoveraccumulation is a good marker of liver steatosis[J].BMC Gas-troenterol, 2010, 10 (25) :98-104.

[60]LYKIARDOPOULOS B, HAGSTROM H, FREDRIKSON M, et al.Development of serum marker models to increase diagnostic accuracy of advanced fibrosis in nonalcoholic fatty liver disease:the new LIN-KI algorithm compared with established algorithms[J].PLo S One, 2016, 11 (12) :e0167776.

[61]FAN JG.Research advances in non-alcoholic fatty liver disease:a review of current status and prospect[J].J Clin Hepatol, 2015, 31 (7) :999-1001. (in Chinese) 范建高.非酒精性脂肪性肝病的研究现状与展望[J].临床肝胆病杂志, 2015, 31 (7) :999-1001.

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