弹性成像联合血清学诊断慢性乙型肝炎肝纤维化的研究现状

何桥; 原文聪; 樊海宁; 徐贺; 任宾

doi:10.3969/j.issn.1001-5256.2021.12.037

弹性成像联合血清学诊断慢性乙型肝炎肝纤维化的研究现状

DOI: 10.3969/j.issn.1001-5256.2021.12.037

何桥^{1, 2},
原文聪^{1, 2},
樊海宁^{1, 2},
徐贺^{1, 2},
任宾^{1, 2, ,}

1.
青海大学附属医院肝胆胰外科，西宁 810001
2.
青海省包虫病研究重点实验室，西宁 810001

基金项目:

青海省科技厅项目 (2020-ZJ-Y01)

详细信息

通信作者:
任宾，35619452@qq.om

中图分类号: R575.2; R512.62
计量
- 文章访问数: 397
- HTML全文浏览量: 192
- PDF下载量: 53
- 被引次数: 0
出版历程
- 收稿日期: 2021-04-29
- 录用日期: 2021-05-20
- 出版日期: 2021-12-20

Current status of research on elastography combined with serology in the diagnosis of chronic hepatitis B liver fibrosis

Qiao HE^{1, 2},
Wencong YUAN^{1, 2},
Haining FAN^{1, 2},
He XU^{1, 2},
Bin REN^{1, 2
, ,}

1.
Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining 810001, China
2.
Qinghai Province Key Laboratory of Hydatid Disease Research, Xining 810001, China

Research funding:

Qinghai Province Science and Technology Department Project (2020-ZJ-Y01)

摘要

摘要: 肝脏穿刺活检是慢性乙型肝炎患者肝纤维化分期诊断金标准，但因其为有创操作，存在一定局限性。目前弹性成像及血清学检查具有便捷、重复、动态检测的优势，在临床上得到广泛应用，检测的准确性已获得众多研究支持，逐渐被各指南及专家共识所推荐。但二者诊断准确性会受到炎症、肥胖、腹水、进食、肋间隙狭窄等因素影响，而弹性成像联合血清学检查可极大提高诊断肝纤维化分期的准确性、灵敏度、特异度。通过查阅国内外相关文献资料，结合文献重点对二者诊断慢性乙型肝炎肝纤维化分期相关问题进行综述。
- 肝硬化 /
- 乙型肝炎, 慢性 /
- 弹性成像技术 /
- 生物标记 /
- 诊断
Abstract: Liver biopsy is the gold standard for the diagnosis of liver fibrosis stage in patients with chronic hepatitis B, but it has certain limitations due to its invasiveness. At present, elastography and serological examination have the advantages of convenience, good repeatability, and dynamic testing and are thus widely used in clinical practice. The accuracy of testing has been supported by a large number of studies, and they have been gradually recommended by various guidelines and expert consensus. However, the diagnostic accuracy of the two methods is affected by factors such as inflammation, obesity, ascites, eating, and intercostal space stenosis, and elastography combined with serological examination can greatly improve the accuracy, sensitivity, and specificity of liver fibrosis staging. With reference to related articles in China and globally, this article reviews the problems of the two methods in the staging of chronic hepatitis B liver fibrosis.
- Liver Cirrhosis /
- Hepatitis B, Chronic /
- Elasticity Imaging Techniques /
- Biomarkers /
- Diagnosis

HTML全文

表 1 FS联合血清学检测对CHB患者肝纤维化的诊断效能

联合方式	AUC	灵敏度	特异度
FS+PLT^[7]	0.95	0.84	0.97
FS+GP73^[8]	0.85	0.77	0.80
FS+TGFβ1+MMP1^[9]	0.90	0.92	0.89
FS+APRI+FIB-4^[10]	0.93	0.89	0.87
FS+APRI+AAR^[11]	0.94	0.70	0.93
FS+APRI+HA^[12]	0.94	0.96	0.90
FS+S100A4^[13]	0.86	0.86	0.77
注：GP73，高尔基体蛋白73；HA, 透明质酸；S100A4, S100钙结合蛋白A4；MMP1, 基质金属蛋白酶1；APRI=[(AST/ULN)×100]/PLT；AAR=AST/ALT；FIB-4=Age×AST(U/L]/[PLT(10⁹/L)×ALT(U/L)^1/2]。

下载: 导出CSV

表 2 FT联合血清学检测对CHB患者肝纤维化的诊断效能

联合方式	S≥2			S≥3			S=4
联合方式	AUC	灵敏度	特异度	AUC	灵敏度	特异度	AUC	灵敏度	特异度
FT+AFC^[19]	0.97	1.00	0.89
FT+APRI+FIB-4^[20]	0.98	0.89	0.92
FT+HA^[21]	0.93	0.89	0.95	0.93	0.91	0.94	0.98	0.96	0.97

下载: 导出CSV

表 3 ARFI联合血清学检测对CHB患者肝纤维化的诊断效能

联合方式	S≥1			S≥2			S=4
联合方式	AUC	灵敏度	特异度	AUC	灵敏度	特异度	AUC	灵敏度	特异度
ARFI+FS^[24]	0.92	0.82	1.00	0.94	0.92	0.88
ARFI+FS+APRI^[25]				0.88	0.94	0.84	0.93	0.93	0.84
ARFI+FI^[26]				0.90	0.94	0.88
注：FI=7.811-3.131In(PLT)+3.131×In(PLT)+0.78×In(GGT)+3.476×In(年龄)-0.014×CHO。

下载: 导出CSV

参考文献(45)

[1]	RAZAVI H. Global epidemiology of viral hepatitis[J]. Gastroenterol Clin North Am, 2020, 49(2): 179-189. DOI: 10.1016/j.gtc.2020.01.001.
[2]	HOU C, HUA Z, XU P, et al. Estimating the prevalence of hepatitis B by wastewater-based epidemiology in 19 cities in China[J]. Sci Total Environ, 2020, 740: 139696. DOI: 10.1016/j.scitotenv.2020.139696.
[3]	YANG XZ, GEN AW, XIAN JC, et al. Diagnostic value of various noninvasive indexes in the diagnosis of chronic hepatic fibrosis[J]. Eur Rev Med Pharmacol Sci, 2018, 22(2): 479-485. DOI: 10.26355/eurrev_201801_14198.
[4]	CHEN X, WEN H, ZHANG X, et al. Development of a simple noninvasive model to predict significant fibrosis in patients with chronic hepatitis B: Combination of ultrasound elastography, serum biomarkers, and individual characteristics[J]. Clin Transl Gastroenterol, 2017, 8(4): e84. DOI: 10.1038/ctg.2017.11.
[5]	LI Y, HUANG YS, WANG ZZ, et al. Systematic review with meta-analysis: The diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B[J]. Aliment Pharmacol Ther, 2016, 43(4): 458-469. DOI: 10.1111/apt.13488.
[6]	OEDA S, TANAKA K, OSHIMA A, et al. Diagnostic accuracy of fibroscan and factors affecting measurements[J]. Diagnostics (Basel), 2020, 10(11): 940. DOI: 10.3390/diagnostics10110940.
[7]	TANG S, MEI TT, LIU YL, et al. Study on non-invasive predictors and models of hepatitis B-related significant liver fibrosis[J]. Beijing Med J, 2019, 41(6): 509-511, 515. DOI: 10.15932/j.0253-9713.2019.06.020. 汤珊, 梅婷婷, 柳雅立, 等. 乙型肝炎相关显著肝纤维化无创预测指标及模型的研究[J]. 北京医学, 2019, 41(6): 509-511, 515. DOI: 10.15932/j.0253-9713.2019.06.020.
[8]	CAO Z, LI Z, WANG H, et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection[J]. Liver Int, 2017, 37(11): 1612-1621. DOI: 10.1111/liv.13536.
[9]	ZENG ZJ, LI MH, WANG XT. Evaluation of serum levels of TGF-β1 and MMP-1 combined with FibroScan in the diagnosis of liver fibrosis caused by hepatitis B[J]. J Trop Med, 2020, 20(3): 376-379. DOI: 10.3969/j.issn.1672-3619.2020.03.024. 曾震军, 李墨航, 王新亭. 血清中TGF-β1、MMP-1表达水平联合FibroScan对乙肝肝纤维化诊断价值[J]. 热带医学杂志, 2020, 20(3): 376-379. DOI: 10.3969/j.issn.1672-3619.2020.03.024.
[10]	SHI RY, ZHEN Z, CHEN YP, et al. The diagnostic value of Fibroscan, APRI and FIB-4 for liver fibrosis and cirrhosis[J]. Chin J Gerontol, 2018, 38(23): 5719-5721. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLXZ201823036.htm 石荣亚, 甄真, 陈宇萍, 等. Fibroscan、APRI、FIB-4对肝纤维化及肝硬化的诊断价值[J]. 中国老年学杂志, 2018, 38(23): 5719-5721. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLXZ201823036.htm
[11]	DAI HF, WANG T, LEI X, et al. Diagnosticefficacy of transient elastography in combination with APRI and AAR in evaluating significant liver fibrosis in patients with chronic hepatitis B[J]. J Prac Hepatol, 2021, 24(2): 196-199. DOI: 10.3969/j.issn.1672-5069.2021.02.012. 代海峰, 王甜, 雷迅, 等. 应用瞬时弹性成像技术联合APRI和AAR指数评估慢性乙型肝炎患者肝纤维化临床价值研究[J]. 实用肝脏病杂志, 2021, 24(2): 196-199. DOI: 10.3969/j.issn.1672-5069.2021.02.012.
[12]	LIU T, CUI XL. The clinical value of FS combined with APRI and HA in the diagnosis of hepatitis B liver fibrosis[J]. Exp Lab Med, 2019, 37(3): 407-409, 418. DOI: 10.3969/j.issn.1674-1129.2019.03.018. 刘涛, 崔晓玲. FS联合APRI、HA诊断乙型肝炎肝纤维化的临床价值分析[J]. 实验与检验医学, 2019, 37(3): 407-409, 418. DOI: 10.3969/j.issn.1674-1129.2019.03.018.
[13]	YAN LB, ZHANG QB, ZHU X, et al. Serum S100 calcium binding protein A4 improves the diagnostic accuracy of transient elastography for assessing liver fibrosis in hepatitis B[J]. Clin Res Hepatol Gastroenterol, 2018, 42(1): 64-71. DOI: 10.1016/j.clinre.2017.05.013.
[14]	GONG H, LI LP. Value of Fibroscan combined with GPR, APRI, NFS or FIB-4 for progressive liver fibrosis in patients with chronic hepatitis B and nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(3): 541-545. DOI: 10.3969/j.issn.1001-5256.2020.03.014. 龚航, 李良平. FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较[J]. 临床肝胆病杂志, 2020, 36(3): 541-545. DOI: 10.3969/j.issn.1001-5256.2020.03.014.
[15]	ZHAO CL, LI SY, ZHANG YJ. The value of fibroscan combined with blood NLR and PDW in predicting the prognosis of liver cirrhosis caused by chronic HBV infection and its relationship with liver function[J]. Imaging Sci Photochem, 2020, 38(4): 748-752. DOI: 10.7517/issn.1674-0475.200325. 赵丛林, 李树义, 张艳君. 瞬时弹性成像技术联合血NLR、PDW对慢性HBV感染相关肝硬化预后的预测价值及与肝功能的关联性研究[J]. 影像科学与光化学, 2020, 38(4): 748-752. DOI: 10.7517/issn.1674-0475.200325.
[16]	ZENG J, SUN WL, CHEN GY, et al. Efficiency of FibroScan and FibroTouch in liver stiffness measurement and fat quantification: A comparative analysis[J]. Chin J Hepatol, 2016, 24(9): 652-658. DOI: 10.3760/cma.j.issn.1007-3418.2016.09.004. 曾静, 孙婉璐, 陈光榆, 等. FibroTouch与FibroScan肝脏硬度和脂肪定量检测效能的比较[J]. 中华肝脏病杂志, 2016, 24(9): 652-658. DOI: 10.3760/cma.j.issn.1007-3418.2016.09.004.
[17]	ZHAO XB, YU J, ZHANG ZH, et al. Stability of FibroTouch in determining liver stiffness measurement and controlled attenuation parameter[J]. J Clin Hepatol, 2020, 36(1): 102-106. DOI: 10.3969/j.issn.1001-5256.2020.01.023. 赵晓博, 于静, 张振华, 等. FibroTouch检测肝硬度值及脂肪衰减值的稳定性分析[J]. 临床肝胆病杂志, 2020, 36(1): 102-106. DOI: 10.3969/j.issn.1001-5256.2020.01.023.
[18]	ZUO ZB, CUI HZ, HUANG CX, et al. Clinical study of FibroTouch and six serological models for assessing the degree of liver fibrosis in patients with chronic hepatitis B[J]. Chin J Hepatol, 2019, 27(6): 430-435. DOI: 10.3760/cma.j.issn.1007-3418.2019.06.008. 左中宝, 崔怀中, 黄从想, 等. FibroTouch与6种肝纤维化血清学模型评估慢性乙型肝炎患者肝纤维化程度的临床研究[J]. 中华肝脏病杂志, 2019, 27(6): 430-435. DOI: 10.3760/cma.j.issn.1007-3418.2019.06.008.
[19]	ZHAO J, ZHAI F, CHENG J, et al. Evaluating the significance of viscoelasticity in diagnosing early-stage liver fibrosis with transient elastography[J]. PLoS One, 2017, 12(1): e0170073. DOI: 10.1371/journal.pone.0170073.
[20]	YU C, LI M, GU YL, et al. Combination of APRI, FIB-4 and FibroTouch for predicting early liver fibrosis in chronic hepatitis B patients[J]. Chin Hepatol, 2018, 23(1): 22-25. DOI: 10.3969/j.issn.1008-1704.2018.01.009. 俞冲, 李民, 顾玉玲, 等. APRI、FIB-4及Fibro Touch联合检测对乙肝肝纤维化的早期预警价值[J]. 肝脏, 2018, 23(1): 22-25. DOI: 10.3969/j.issn.1008-1704.2018.01.009.
[21]	LIU F, WEI L, WANG SS, et al. Diagnostic value of transient elastography technology combined with serological indicator for liver fibrosis in patients with chronic hepatitis B[J]. Chin Gen Pract, 2016, 19(25): 3039-3044. DOI: 10.3969/j.issn.1007-9572.2016.25.008. 刘芳, 魏琳, 王珊珊, 等. 瞬时弹性成像技术联合血清学指标对慢性乙型肝炎肝纤维化的诊断价值研究[J]. 中国全科医学, 2016, 19(25): 3039-3044. DOI: 10.3969/j.issn.1007-9572.2016.25.008.
[22]	PARK MS, KIM SW, YOON KT, et al. Factors influencing the diagnostic accuracy of acoustic radiation force impulse elastography in patients with chronic hepatitis B[J]. Gut Liver, 2016, 10(2): 275-282. DOI: 10.5009/gnl14391.
[23]	TSENG CH, CHANG CY, MO LR, et al. Acoustic radiation force impulse elastography with APRI and FIB-4 to identify significant liver fibrosis in chronic hepatitis B patients[J]. Ann Hepatol, 2018, 17(5): 789-794. DOI: 10.5604/01.3001.0012.3137.
[24]	GAO MR, DONG XQ. Diagnostic value of acoustic radiation force impulse combined with transient elastography for inflammatory liver fibrosis[J/CD]. Chin J Med Ultrasound(Electronic edition), 2019, 16(7): 549-554. DOI: 10.3877/cma.j.issn.1672-6448.2019.07.010. 高明茹, 董晓秋. 声脉冲辐射力成像联合瞬时弹性成像对炎性肝纤维化的诊断价值[J/CD]. 中华医学超声杂志(电子版), 2019, 16(7): 549-554. DOI: 10.3877/cma.j.issn.1672-6448.2019.07.010.
[25]	DONG CF, FENG C, HUANG T, et al. Elastography combined with biochemical index for assessment of hepatic fibrosis grading in chronic hepatitis B patients[J]. Chin J Ultrasound Med, 2018, 34(7): 623-626. DOI: 10.3969/j.issn.1002-0101.2018.07.016. 董常峰, 冯程, 黄婷, 等. 弹性成像联合血生化指标评估慢性乙型肝炎肝纤维化程度[J]. 中国超声医学杂志, 2018, 34(7): 623-626. DOI: 10.3969/j.issn.1002-0101.2018.07.016.
[26]	DONG DR, HAO MN, LI C, et al. Acoustic radiation force impulse elastography, FibroScan^®, Forns' index and their combination in the assessment of liver fibrosis in patients with chronic hepatitis B, and the impact of inflammatory activity and steatosis on these diagnostic methods[J]. Mol Med Rep, 2015, 11(6): 4174-4182. DOI: 10.3892/mmr.2015.3299.
[27]	BARR RG, FERRAIOLI G, PALMERI ML, et al. Elastography assessment of liver fibrosis: Society of radiologists in ultrasound consensus conference statement[J]. Ultrasound Q, 2016, 32(2): 94-107. DOI: 10.1097/RUQ.0000000000000209.
[28]	KENNEDY P, WAGNER M, CASTÉRA L, et al. Quantitative elastography methods in liver disease: Current evidence and future directions[J]. Radiology, 2018, 286(3): 738-763. DOI: 10.1148/radiol.2018170601.
[29]	HERRMANN E, de LÉDINGHEN V, CASSINOTTO C, et al. Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis[J]. Hepatology, 2018, 67(1): 260-272. DOI: 10.1002/hep.29179.
[30]	ZHUANG Y, DING H, ZHANG Y, et al. Two- dimensional shear-wave elastography performance in the noninvasive evaluation of liver fibrosis in patients with chronic hepatitis B: Comparison with serum fibrosis indexes[J]. Radiology, 2017, 283(3): 873-882. DOI: 10.1148/radiol.2016160131.
[31]	OSMAN AM, EL SHIMY A, ABD EL AZIZ MM. 2D shear wave elastography (SWE) performance versus vibration-controlled transient elastography (VCTE/fibroscan) in the assessment of liver stiffness in chronic hepatitis[J]. Insights Imaging, 2020, 11(1): 38. DOI: 10.1186/s13244-020-0839-y.
[32]	YAO TT, PAN J, QIAN JD, et al. Shear wave elastography may be sensitive and more precise than transient elastography in predicting significant fibrosis[J]. World J Clin Cases, 2020, 8(17): 3730-3742. DOI: 10.12998/wjcc.v8.i17.3730.
[33]	XU B, ZHOU NM, CAO WT, et al. Evaluation of elastography combined with serological indexes for hepatic fibrosis in patients with chronic hepatitis B[J]. World J Gastroenterol, 2018, 24(37): 4272-4280. DOI: 10.3748/wjg.v24.i37.4272.
[34]	LIU J, ZHAO J, ZHANG Y, et al. Noninvasive assessment of liver fibrosis stage using ultrasound-based shear wave velocity measurements and serum algorithms in patients with viral hepatitis B: A retrospective cohort study[J]. J Ultrasound Med, 2017, 36(2): 285-293. DOI: 10.7863/ultra.16.01069.
[35]	WU T, WANG P, ZHANG T, et al. Comparison of two-dimensional shear wave elastography and real-time tissue elastography for assessing liver fibrosis in chronic hepatitis B[J]. Dig Dis, 2016, 34(6): 640-649. DOI: 10.1159/000448825.
[36]	WANG T, SHAO C, ZHANG G, et al. Real-time elastography (RTE): A valuable sonography-based non-invasive method for the assessment of liver fibrosis in chronic hepatitis B[J]. Abdom Radiol (NY), 2017, 42(11): 2632-2638. DOI: 10.1007/s00261-017-1186-4.
[37]	ZHAI Z, ZHANG CX. Application of real-time tissue elastography and FibroScan in evaluation of liver fibrosis[J]. Acta Univ Med Anhui, 2019, 54(5): 817-820. DOI: 10.19405/j.cnki.issn1000-1492.2019.05.034. 翟哲, 张超学. 实时与瞬时弹性成像在肝纤维化评价中的应用[J]. 安徽医科大学学报, 2019, 54(5): 817-820. DOI: 10.19405/j.cnki.issn1000-1492.2019.05.034.
[38]	DU XL, ZHANG JW, YUE ML, et al. Value of real-time tissue elastography and contrast-enhanced ultrasonography in liver fibrosis assessment in patients with chronic hepatitis B[J/CD]. Chin J Med Ultrasound(Electronic edition), 2018, 15(10): 767-772. DOI: 10.3877/cma.j.issn.1672-6448.2018.10.008. 杜昕苓, 张久维, 岳民璐, 等. 实时组织弹性成像联合超声造影技术在慢性乙型肝炎患者肝纤维化诊断中的应用[J/CD]. 中华医学超声杂志(电子版), 2018, 15(10): 767-772. DOI: 10.3877/cma.j.issn.1672-6448.2018.10.008.
[39]	XU SH, LI Q, HU YP, et al. Development of a model based on biochemical, real-time tissue elastography and ultrasound data for the staging of liver fibrosis and cirrhosis in patients with chronic hepatitis B[J]. Mol Med Rep, 2016, 14(4): 3609-3619. DOI: 10.3892/mmr.2016.5682.
[40]	JANG HJ, MIN JH, LEE JE, et al. Assessment of liver fibrosis with gadoxetic acid-enhanced MRI: Comparisons with transient elastography, ElastPQ, and serologic fibrosis markers[J]. Abdom Radiol (NY), 2019, 44(8): 2769-2780. DOI: 10.1007/s00261-019-02041-z.
[41]	IDILMAN IS, LI J, YIN M, et al. MR elastography of liver: Current status and future perspectives[J]. Abdom Radiol (NY), 2020, 45(11): 3444-3462. DOI: 10.1007/s00261-020-02656-7.
[42]	SHI Y, XIA F, LI QJ, et al. Magnetic resonance elastography for the evaluation of liver fibrosis in chronic hepatitis B and C by using both gradient-recalled echo and spin-echo echo planar imaging: A prospective study[J]. Am J Gastroenterol, 2016, 111(6): 823-833. DOI: 10.1038/ajg.2016.56.
[43]	PATEL K, SEBASTIANI G. Limitations of non-invasive tests for assessment of liver fibrosis[J]. JHEP Rep, 2020, 2(2): 100067. DOI: 10.1016/j.jhepr.2020.100067.
[44]	REN X, ZHANG L, XIA S, et al. A new visual transient elastography technique for grading liver fibrosis in patients with chronic hepatitis B[J]. Ultrasound Q, 2020, 37(2): 105-110. DOI: 10.1097/RUQ.0000000000000509.
[45]	NGUYEN H, WIMMER R, LE VQ, et al. Metabolic fingerprint of progression of chronic hepatitis B: Changes in the metabolome and novel diagnostic possibilities[J]. Metabolomics, 2021, 17(2): 16. DOI: 10.1007/s11306-020-01767-y.