肝活检病理学指标在肝硬化门静脉高压症诊断中的应用

许雅洁; 尤文铮; 任万雷; 龙泉河; 姜相君; 胡豆豆

doi:10.3969/j.issn.1001-5256.2021.12.042

肝活检病理学指标在肝硬化门静脉高压症诊断中的应用

DOI: 10.3969/j.issn.1001-5256.2021.12.042

许雅洁^{1, 2a},
尤文铮^2b,
任万雷³,
龙泉河^2c,
姜相君^2a,
胡豆豆^2a, ,

1.
大连医科大学研究生院，辽宁大连 116044
2a.
青岛市市立医院消化内二科，山东青岛 266000
2b.
青岛市市立医院消化内科，山东青岛 266000
2c.
青岛市市立医院普外科，山东青岛 266000
3.
青岛大学附属青岛市中心医院中医一科，山东青岛 266042

基金项目:

国家自然科学基金青年基金 (81800543)

详细信息

通信作者:
胡豆豆，hudoudou1984@163.com

中图分类号: R575.2
计量
- 文章访问数: 531
- HTML全文浏览量: 202
- PDF下载量: 48
- 被引次数: 0
出版历程
- 收稿日期: 2021-05-12
- 录用日期: 2021-05-20
- 出版日期: 2021-12-20

Application of pathological indicators based on liver biopsy in the diagnosis of cirrhotic portal hypertension

Yajie XU^{1, 2a},
Wenzheng YOU^2b,
Wanlei REN³,
Quanhe LONG^2c,
Xiangjun JIANG^2a,
Doudou HU^{2a
, ,}

1.
Graduate School of Dalian Medical University, Dalian, Liaoning 116044, China
2a.
Second Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, China
2b.
Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, China
2c.
Department of General Surgery, Qingdao Municipal Hospital, Qingdao, Shandong 266000, China
3.
First Department of Traditional Chinese Medicine, Qingdao Central Hospital Affiliated to Qingdao University, Qingdao, Shandong 266042, China

Research funding:

National Natural Science Foundation of China Young Scientist Fund (81800543)

摘要

摘要: 肝静脉压力梯度(HVPG)是诊断门静脉高压症以及判断其严重程度的“金标准”，但因其有创性、操作技术难度大，限制了其在临床中的广泛开展。通过非侵入性方法替代HVPG是目前研究的热点，但现有的血清学及影像学方法的准确度仍有待商榷，尚不能在临床中完全替代HVPG。肝活检已在临床中广泛开展多年，是确诊某些肝脏疾病不可或缺的方法。近来研究发现肝穿刺后的病理学指标，如胶原面积、纤维间隔厚度、结节大小、微血管密度及胆管、淋巴管密度和面积等，不仅能判断肝纤维化的严重程度，而且与门静脉压力也有良好的相关性。这对诊断肝硬化门静脉高压症及评估门静脉高压症严重程度提供了新的思路。
- 肝硬化 /
- 高血压，门静脉 /
- 活组织检查, 针吸 /
- 诊断
Abstract: Hepatic venous pressure gradient (HVPG) is the "gold standard" for diagnosing portal hypertension and determining its severity, but its wide clinical application is limited due to its invasiveness and difficulties in operation. The replacement of HVPG by noninvasive methods has become a research hotspot in recent years; however, the accuracy of the existing serological and imaging methods remains to be discussed, and such methods cannot completely replace HVPG in clinical practice. Liver biopsy has been widely used in clinical practice for many years and is still an indispensable method for the diagnosis of some liver diseases. Recent studies have found that several pathological indicators after liver biopsy, such as collagen area, fibrous septal thickness, nodule size, microvascular density, and density and area of bile ducts and lymphatic vessels, can not only judge the severity of liver fibrosis, but also have a good correlation with portal venous pressure, which provides new ideas for diagnosing cirrhotic portal hypertension and evaluating the severity of portal hypertension.
- Liver Cirrhosis /
- Hypertension, Portal /
- Biopsy, Needle /
- Diagnosis

HTML全文

参考文献(48)

[1]	BERZIGOTTI A. Advances and challenges in cirrhosis and portal hypertension[J]. BMC Med, 2017, 15(1): 200. DOI: 10.1186/s12916-017-0966-6.
[2]	GROSS M. Liver cirrhosis and the most common complications: Diagnosis and treatment[J]. MMW Fortschr Med, 2015, 157(Suppl 1): 75-79. DOI: 10.1007/s15006-015-2550-3.
[3]	de FRANCHIS R, Baveno Ⅵ Faculty. Expanding consensus in portal hypertension: Report of the Baveno Ⅵ Consensus Workshop: Stratifying risk and individualizing care for portal hypertension[J]. J Hepatol, 2015, 63(3): 743-752. DOI: 10.1016/j.jhep.2015.05.022.
[4]	YOO JJ, KIM SG. HVPG as a predictor of mortality in non-critically-ill cirrhotic patients[J]. J Korean Med Sci, 2019, 34(33): e235. DOI: 10.3346/jkms.2019.34.e235.
[5]	AGARWAL S, SHARMA S, ANAND A, et al. Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study[J]. JGH Open, 2021, 5(1): 73-80. DOI: 10.1002/jgh3.12449.
[6]	POONKHUM R, SHOWPITTAPORNCHAI U, PRADIDARCHEEP W. Collagen arrangement in space of Disse correlates with fluid flow in normal and cirrhotic rat livers[J]. Microsc Res Tech, 2015, 78(2): 187-193. DOI: 10.1002/jemt.22460.
[7]	WEISKIRCHEN R, WEISKIRCHEN S, TACKE F. Recent advances in understanding liver fibrosis: Bridging basic science and individualized treatment concepts[J]. F1000Res, 2018, 7. DOI: 10.12688/f1000research.14841.1.
[8]	WEISKIRCHEN R, WEISKIRCHEN S, TACKE F. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications[J]. Mol Aspects Med, 2019, 65: 2-15. DOI: 10.1016/j.mam.2018.06.003.
[9]	AYCOCK RS, SEYER JM. Collagens of normal and cirrhotic human liver[J]. Connect Tissue Res, 1989, 23(1): 19-31. DOI: 10.3109/03008208909103901.
[10]	HU DD, HABIB S, LI XM, et al. Angiogenesis: A new surrogate histopathological marker is capable of differentiating between mild and significant portal hypertension[J]. Histol Histopathol, 2015, 30(2): 205-212. DOI: 10.14670/HH-30.205.
[11]	CALVARUSO V, BURROUGHS AK, STANDISH R, et al. Computer-assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient[J]. Hepatology, 2009, 49(4): 1236-1244. DOI: 10.1002/hep.22745.
[12]	TSOCHATZIS E, BRUNO S, ISGRO G, et al. Collagen proportionate area is superior to other histological methods for sub-classifying cirrhosis and determining prognosis[J]. J Hepatol, 2014, 60(5): 948-954. DOI: 10.1016/j.jhep.2013.12.023.
[13]	SETHASINE S, JAIN D, GROSZMANN RJ, et al. Quantitative histological-hemodynamic correlations in cirrhosis[J]. Hepatology, 2012, 55(4): 1146-1153. DOI: 10.1002/hep.24805.
[14]	ISGRO G, CALVARUSO V, ANDREANA L, et al. The relationship between transient elastography and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis[J]. J Gastroenterol, 2013, 48(8): 921-929. DOI: 10.1007/s00535-012-0694-9.
[15]	NIELSEN K, CLEMMESEN JO, VASSILIADIS E, et al. Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction[J]. APMIS, 2014, 122(12): 1213-1222. DOI: 10.1111/apm.12287.
[16]	KUMAR M, SAKHUJA P, KUMAR A, et al. Histological subclassification of cirrhosis based on histological-haemodynamic correlation[J]. Aliment Pharmacol Ther, 2008, 27(9): 771-779. DOI: 10.1111/j.1365-2036.2008.03653.x.
[17]	RASTOGI A, MAIWALL R, BIHARI C, et al. Cirrhosis histology and Laennec staging system correlate with high portal pressure[J]. Histopathology, 2013, 62(5): 731-741. DOI: 10.1111/his.12070.
[18]	NAGULA S, JAIN D, GROSZMANN RJ, et al. Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis[J]. J Hepatol, 2006, 44(1): 111-117. DOI: 10.1016/j.jhep.2005.07.036.
[19]	COSAR AM, YAKAR T, SERIN E, et al. The relationship between fibrosis and nodule structure and esophageal varices[J]. Turk J Gastroenterol, 2019, 30(7): 624-629. DOI: 10.5152/tjg.2019.18665.
[20]	XUAN R, ZHAO X, JIAN J, et al. Phase-contrast computed tomography: A correlation study between portal pressure and three dimensional microvasculature of ex vivo liver samples from carbon tetrachloride-induced liver fibrosis in rats[J]. Microvasc Res, 2019, 125: 103884. DOI: 10.1016/j.mvr.2019.103884.
[21]	GARBUZENKO DV, AREFYEV NO, KAZACHKOV EL. Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives[J]. World J Gastroenterol, 2018, 24(33): 3738-3748. DOI: 10.3748/wjg.v24.i33.3738.
[22]	LI H. Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma[J]. Expert Rev Gastroenterol Hepatol, 2021, 15(3): 217-233. DOI: 10.1080/17474124.2021.1842732.
[23]	ZADOROZHNA M, DI GIOIA S, CONESE M, et al. Neovascularization is a key feature of liver fibrosis progression: Anti-angiogenesis as an innovative way of liver fibrosis treatment[J]. Mol Biol Rep, 2020, 47(3): 2279-2288. DOI: 10.1007/s11033-020-05290-0.
[24]	GANA JC, SERRANO CA, LING SC. Angiogenesis and portal-systemic collaterals in portal hypertension[J]. Ann Hepatol, 2016, 15(3): 303-313. DOI: 10.5604/16652681.1198799.
[25]	WEIDNER N. Intratumor microvessel density as a prognostic factor in cancer[J]. Am J Pathol, 1995, 147(1): 9-19. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1869874/pdf/amjpathol00043-0015.pdf?origin=publication_detail
[26]	WU Y, LI Z, XIU AY, et al. Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice[J]. Drug Des Devel Ther, 2019, 13: 2667-2676. DOI: 10.2147/DDDT.S210797.
[27]	SUN M, LV W, ZHAO X, et al. Vascular branching geometry relating to portal hypertension: A study of liver microvasculature in cirrhotic rats by X-ray phase-contrast computed tomography[J]. Quant Imaging Med Surg, 2020, 10(1): 116-127. DOI: 10.21037/qims.2019.11.04.
[28]	TANAKA M, IWAKIRI Y. Lymphatics in the liver[J]. Curr Opin Immunol, 2018, 53: 137-142. DOI: 10.1016/j.coi.2018.04.028.
[29]	PUPULIM LF, VILGRAIN V, RONOT M, et al. Hepatic lymphatics: Anatomy and related diseases[J]. Abdom Imaging, 2015, 40(6): 1997-2011. DOI: 10.1007/s00261-015-0350-y.
[30]	IWAKIRI Y. Pathophysiology of portal hypertension[J]. Clin Liver Dis, 2014, 18(2): 281-291. DOI: 10.1016/j.cld.2013.12.001.
[31]	TANAKA M, IWAKIRI Y. The hepatic lymphatic vascular system: Structure, function, markers, and lymphangiogenesis[J]. Cell Mol Gastroenterol Hepatol, 2016, 2(6): 733-749. DOI: 10.1016/j.jcmgh.2016.09.002.
[32]	BARROWMAN JA, GRANGER DN. Effects of experimental cirrhosis on splanchnic microvascular fluid and solute exchange in the rat[J]. Gastroenterology, 1984, 87(1): 165-172. http://www.valueinhealthjournal.com/article/0016-5085(84)90140-9/pdf
[33]	VOLLMAR B, WOLF B, SIEGMUND S, et al. Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis[J]. Am J Pathol, 1997, 151(1): 169-175. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857941/pdf/amjpathol00019-0168.pdf
[34]	TANAKA M, IWAKIRI Y. The hepatic lymphatic vascular system: Structure, function, markers, and lymphangiogenesis[J]. Cell Mol Gastroenterol Hepatol, 2016, 2(6): 733-749. DOI: 10.1016/j.jcmgh.2016.09.002.
[35]	YAMAUCHI Y, MICHITAKA K, ONJI M. Morphometric analysis of lymphatic and blood vessels in human chronic viral liver diseases[J]. Am J Pathol, 1998, 153(4): 1131-1137. DOI: 10.1016/S0002-9440(10)65657-X.
[36]	TAMBURINI B, FINLON JM, GILLEN AE, et al. Chronic liver disease in humans causes expansion and differentiation of liver lymphatic endothelial cells[J]. Front Immunol, 2019, 10: 1036. DOI: 10.3389/fimmu.2019.01036.
[37]	OIKAWA H, MASUDA T, SATO S, et al. Changes in lymph vessels and portal veins in the portal tract of patients with idiopathic portal hypertension: A morphometric study[J]. Hepatology, 1998, 27(6): 1607-1610. DOI: 10.1002/hep.510270621.
[38]	PARK SW, KIM TH, HAM SY, et al. Clinical implications of thoracic duct dilatation in patients with chronic liver disease[J]. Medicine (Baltimore), 2020, 99(22): e19889. DOI: 10.1097/MD.0000000000019889.
[39]	DAINA CM, DAINA LG, BONTA M, et al. Study concerning the histopathological changes in chronic hepatopathies[J]. Rom J Morphol Embryol, 2017, 58(1): 153-159. http://www.rjme.ro/RJME/resources/files/580117153159.pdf
[40]	NGUYEN T, TANG W, NAN L, et al. The role of bile duct reactive change in the pathogenesis of liver fibrosis due to hepatitis C[J]. Exp Mol Pathol, 2005, 79(2): 95-99. DOI: 10.1016/j.yexmp.2005.04.010.
[41]	GLASER SS, GAUDIO E, MILLER T, et al. Cholangiocyte proliferation and liver fibrosis[J]. Expert Rev Mol Med, 2009, 11: e7. DOI: 10.1017/S1462399409000994.
[42]	SATO K, MARZIONI M, MENG F, et al. Ductular reaction in liver diseases: Pathological mechanisms and translational significances[J]. Hepatology, 2019, 69(1): 420-430. DOI: 10.1002/hep.30150.
[43]	HUBEL E, SAROHA A, PARK WJ, et al. Sortilin deficiency reduces ductular reaction, hepatocyte apoptosis, and liver fibrosis in cholestatic-induced liver injury[J]. Am J Pathol, 2017, 187(1): 122-133. DOI: 10.1016/j.ajpath.2016.09.005.
[44]	HALL C, SATO K, WU N, et al. Regulators of cholangiocyte proliferation[J]. Gene Expr, 2017, 17(2): 155-171. DOI: 10.3727/105221616X692568.
[45]	RÓKUSZ A, VERES D, SZVCS A, et al. Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models[J]. PLoS One, 2017, 12(4): e0176518. DOI: 10.1371/journal.pone.0176518.
[46]	WOOD MJ, GADD VL, POWELL LW, et al. Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression[J]. Hepatology, 2014, 59(3): 848-857. DOI: 10.1002/hep.26706.
[47]	CLOUSTON AD, POWELL EE, WALSH MJ, et al. Fibrosis correlates with a ductular reaction in hepatitis C: Roles of impaired replication, progenitor cells and steatosis[J]. Hepatology, 2005, 41(4): 809-818. DOI: 10.1002/hep.20650.
[48]	RICHARDSON MM, JONSSON JR, POWELL EE, et al. Progressive fibrosis in nonalcoholic steatohepatitis: Association with altered regeneration and a ductular reaction[J]. Gastroenterology, 2007, 133(1): 80-90. DOI: 10.1053/j.gastro.2007.05.012.