非酒精性脂肪性肝病并发门静脉高压的研究进展

李敏; 毛小荣

doi:10.3969/j.issn.1001-5256.2018.08.047

非酒精性脂肪性肝病并发门静脉高压的研究进展

DOI: 10.3969/j.issn.1001-5256.2018.08.047

李敏,
毛小荣

兰州大学第一医院感染科

基金项目:

甘肃省卫生行业科研计划项目(GSWSKY2017-45)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 1644
- HTML全文浏览量: 27
- PDF下载量: 388
- 被引次数: 0
出版历程
- 收稿日期: 2018-03-22
- 出版日期: 2018-08-20

Research advances in portal hypertension in patients with nonalcoholic fatty liver disease

Department of Infectious Diseases, The First Hospital of Lanzhou University

Research funding:

摘要

摘要: 非酒精性脂肪性肝病(NAFLD)进展至肝硬化通常伴有临床显著的门静脉高压症,其主要原因是肝内血管阻力增加,其发病机制至今尚未明确。总结了非肝硬化性NAFLD门静脉高压的研究现状以及门静脉高压发生过程中的细胞和分子作用机制,旨在为深入研究NAFLD新的预防和治疗策略提供理论基础。
- 非酒精性脂肪性肝病 /
- 门静脉高压 /
- 内皮功能障碍 /
- 肝内血管阻力 /
- 综述
Abstract: Nonalcoholic fatty liver disease ( NAFLD) is often complicated by clinically significant portal hypertension ( PHT) during its progression to liver cirrhosis, which is primarily caused by increased intrahepatic vascular resistance. The pathogenesis of PHT in NAFLD remains unclear. This article summarizes the current research status of PHT in NAFLD and related cellular and molecular mechanisms in the development of PHT, in order to provide a theoretical basis for novel preventive and therapeutic strategies for NAFLD.
- nonalcoholic fatty liver disease /
- portal hypertension /
- endothelial dysfunction /
- intrahepatic vascular resistance /
- review

HTML全文

参考文献(37)

[1]KIM CH, YOUNOSSI ZM.Nonalcoholic fatty liver disease:A manifestation of the metabolic syndrome[J].Cleve Clin J Med, 2008, 75 (10) :721-728.

[2]GOH GB, MCCULLOUGH AJ.Natural history of nonalcoholic fatty liver disease[J].Dig Dis Sci, 2016, 61 (5) :1226-1233.

[3]HAGSTROM H, NASR P, EKSTEDT M, et al.Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD[J].J Hepatol, 2017, 67 (6) :1265-1273.

[4]SANYAL AJ, BOSCH J, BLEI A, et al.Portal hypertension and its complications[J].Gastroenterology, 2008, 134 (6) :1715-1728.

[5]FRANCQUE S, VERRIJKEN A, MERTENS I, et al.Noncirrhotic human nonalcoholic fatty liver disease induces portal hypertension in relation to the histological degree of steatosis[J].Eur J Gastroenterol Hepatol, 2010, 22 (12) :1449-1457.

[6]MUELLER S.Does pressure cause liver cirrhosis?The sinusoidal pressure hypothesis[J].World J Gastroenterol, 2016, 22 (48) :10482-10501.

[7]VOLLMAR B, MENGER MD.The hepatic microcirculation:Mechanistic contributions and therapeutic targets in liver injury and repair[J].Physiol Rev, 2009, 89 (4) :1269-1339.

[8]FARRELL GC, TEOH NC, Mc CUSKEY RS.Hepatic microcirculation in fatty liver disease[J].Anat Rec (Hoboken) , 2008, 291 (6) :684-692.

[9]STRAUSS E, VALLA D.Non-cirrhotic portal hypertension-concept, diagnosis and clinical management[J].Clin Res Hepatol Gastroenterol, 2014, 38 (5) :564-569.

[10]SILVA-JUNIOR G, BAIGES A, TURON F, et al.The prognostic value of hepatic venous pressure gradient in patients with cirrhosis is highly dependent on the accuracy of the technique[J].Hepatology, 2015, 62 (5) :1584-1592.

[11]WADA K, FUJIMOTO K, FUJIKAWA Y, et al.Sinusoidal stenosis as the cause of portal hypertension in choline deficient diet induced fatty cirrhosis of the rat liver[J].Acta Pathol Jpn, 1974, 24 (2) :207-217.

[12]SUN CK, ZHANG XY, WHEATLEY AM.Increased NAD (P) H fluorescence with decreased blood flow in the steatotic liver of the obese Zucker rat[J].Microvasc Res, 2003, 66 (1) :15-21.

[13]BALCI A, KARAZINCIR S, SUMBAS H, et al.Effects of diffuse fatty infiltration of the liver on portal vein flow hemodynamics[J].J Clin Ultrasound, 2008, 36 (3) :134-140.

[14]MENDES FD, SUZUKI A, SANDERSON SO, et al.Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease[J].Clin Gastroenterol Hepatol, 2012, 10 (9) :1022-1033.

[15]VONGHIA L, MAGRONE T, VERRIJKEN A, et al.Peripheral and hepatic vein cytokine levels in correlation with non-alcoholic fatty liver disease (NAFLD) -related metabolic, histological, and haemodynamic features[J].PLo S One, 2015, 10 (11) :e0143380.

[16]IJAZ S, YANG W, WINSLET MC, et al.Impairment of hepatic microcirculation in fatty liver[J].Microcirculation, 2003, 10 (6) :447-456.

[17]HIJMANS BS, GREFHORST A, OOSTERVEER MH, et al.Zonation of glucose and fatty acid metabolism in the liver:Mechanism and metabolic consequences[J].Biochimie, 2014, 96:121-129.

[18]STRAUB BK, STOEFEL P, HEID H, et al.Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis[J].Hepatology, 2008, 47 (6) :1936-1946.

[19]CALDWELL S, IKURA Y, DIAS D, et al.Hepatocellular ballooning in NASH[J].J Hepatol, 2010, 53 (4) :719-723.

[20]RANGWALA F, GUY CD, LU J, et al.Increased production of sonic hedgehog by ballooned hepatocytes[J].J Pathol, 2011, 224 (3) :401-410.

[21]AIRD WC.Phenotypic heterogeneity of the endothelium:II.Representative vascular beds[J].Circ Res, 2007, 100 (2) :174-190.

[22]REYNAERT H, URBAIN D, GEERTS A.Regulation of sinusoidal perfusion in portal hypertension[J].Anat Rec (Hoboken) , 2008, 291 (6) :693-698.

[23]PASARIN M, LA MURA V, GRACIA-SANCHO J, et al.Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD[J].PLo S One, 2012, 7 (4) :e32785.

[24]FRIEDMAN SL.Hepatic stellate cells:Protean, multifunctional, and enigmatic cells of the liver[J].Physiol Rev, 2008, 88 (1) :125-172.

[25]MARRONE G, SHAH VH, GRACIA-SANCHO J.Sinusoidal communication in liver fibrosis and regeneration[J].J Hepatol, 2016, 65 (3) :608-617.

[26]SZABO G, DOLGANIUC A, MANDREKAR P.Pattern recognition receptors:A contemporary view on liver diseases[J].Hepatology, 2006, 44:287-298.

[27]MAHER JJ, LEON P, RYAN JC.Beyond insulin resistance:Innate immunity in nonalcoholic steatohepatitis[J].Hepatology, 2008, 48:670-678.

[28]KIETZMANN T, GORLACH A.Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression[J].Semin Cell Dev Biol, 2005, 16 (4-5) :474-486.

[29]MIYAO M, KOTANI H, ISHIDA T, et al.Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression[J].Lab Invest, 2015, 95 (10) :1130-1144.

[30]IWAKIRI Y, SHAH V, ROCKEY DC.Vascular pathobiology in chronic liver disease and cirrhosis-current status and future directions[J].J Hepatol, 2014, 61 (4) :912-924.

[31]GILL RM, BELT P, WILSON L, et al.Centrizonal arteries and microvessels in nonalcoholic steatohepatitis[J].Am J Surg Pathol, 2011, 35 (9) :1400-1404.

[32]POVERO D, EGUCHI A, NIESMAN IR, et al.Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells[J].Sci Signal, 2013, 6 (296) :ra88.

[33]LALEMAN W, LANDEGHEM L, WILMER A, et al.Portal hypertension:From pathophysiology to clinical practice[J].Liver Int, 2005, 25 (6) :1079-1090.

[34]FRANCQUE S, WAMUTU S, CHATTERJEE S, et al.Non-alcoholic steatohepatitis induces non-fbrosis-related portal hypertension associated with splanchnic vasodilation and signs of a hyperdynamic circulation in vitro and in vivo in a rat model[J].Liver Int, 2010, 30 (3) :365-375.

[35]LIU JQ, ZHOU SM.Rerearch advances in intestinal flora in nonalcoholic fatty liver disease[J].J Clin Hepatol, 2017, 33 (12) :2453-2456. (in Chinese) 刘嘉琪, 周少明.非酒精性脂肪性肝病肠道菌群的研究进展[J].临床肝胆病杂志, 2017, 33 (12) :2453-2456.

[36]PARSEUS A, SOMMER N, SOMMER F, et al.Microbiota-induced obesity requires farnesoid X receptor[J].Gut, 2017, 66 (3) :429-437.

[37]ZHU Q, ZOU L, JAGAVELU K, et al.Intestinal decontamination inhibits TLR4 dependent fbronectin-mediated cross-talk between stellate cells and endothelial cells in liver fbrosis in mice[J].J Hepatol, 2012, 56 (4) :893-899.

施引文献

资源附件(0)

访问统计