摘要： 门脉性肺动脉高压(PPHTN)是肝病患者在门静脉高压基础上出现以肺动脉压升高和肺血管阻力增加为特点的疾病,是门静脉高压的严重并发症,其发病机制尚不明确,可能与高动力循环状态、血管活性介质失衡、原位血栓形成、遗传变异、系统性炎症反应、免疫损伤、氧化应激等因素相关,病死率较高。目前尚无特异性的治疗药物,肝移植是唯一有效的治疗手段,未来进一步探究PPHTN的发病机制,将为其治疗提供新方法。本文重点介绍POPH的流行病学、发病机制、临床特征、诊断及治疗进展。
王胜兰. 门脉性肺动脉高压的临床特征及其诊疗研究进展[J]. 肝脏, 2022, 27(2): 136-141.
| [1] Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J,2019,53:1801913. [2] Edwards BS, Weir EK, Edwards WD, et al. Coexistent pulmonary and portal hypertension: morphologic and clinical features. J Am Coll Cardiol,1987,10: 1233-1238. [3] Jonigk D, Golpon H, Bockmeyer CL, et al. Plexiform lesions in pulmonary arterial hypertension composition, architecture, and microenvironment. Am J Pathol,2011,179: 167-179. [4] Mantz FA Jr, Craige E. Portal axis thrombosis with spontaneous portacaval shunt and resultant cor pulmonale. AMA Arch Pathol,1951,52: 91-97. [5] Ba Desch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. CHEST, 2010,137:376-387. [6] Thomas C, Glinskii V, de Jesus Perez V, et al. Portopulmonary Hypertension: From Bench to Bedside. Front Med (Lausanne),2020,7: 569413. [7] Segraves JM, Cartin-Ceba R, Leise MD, et al. Relationship between portopulmonary hypertension and splenectomy: Mayo Clinic experience and literature review. Hepatol Res,2017. 48:E340-E346. [8] Panos RJ, Baker SK. Mediators, cytokines, and growth factors in liver-lung interactions. Clin Chest Med,1996,17: 151-169. [9] Lv Y, Han G, Fan D. Portopulmonary hypertension. Scand J Gastroenterol,2016,51: 795-806. [10] Raevens S, Geerts A, Van Steenkiste C, et al. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int,2015,35: 1646-1660. [11] Savale L, Watherald J, Sitbon O. Portopulmonary Hypertension. Semin Respir Crit Care Med,2017,38: 651-661. [12] DuBrock HM, Channick RN, Krowka MJ. What's new in the treatment of portopulmonary hypertension. Expert Rev Gastroenterol Hepatol,2015,9: 983-992. [13] Budhiraja R, Hassoun PM. Portopulmonary hypertension: a tale of two circulations. Chest,2003,123: 562-576. [14] Wong F. Portopulmonary hypertension in cirrhosis: the pathogenetic challenge. Gut,2005,54: 309. [15] Shao D, Park JE, Wort SJ. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol Res,2011,63: 504-511. [16] Cartin-Ceba R, Krowka MJ. Pulmonary Complications of Portal Hypertension. Clin Liver Dis,2019,23: 683-711. [17] Fussner LA, Krowka MJ. Current Approach to the Diagnosis and Management of Portopulmonary Hypertension. Curr Gastroenterol Rep,2016,18: 29. [18] Humbert M, Guignabert C, Bonnet S, et al. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J,2019,53:1801887. [19] Krowka MJ, Fallon MB, Kawut SM, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation,2016,100: 1440-1452. [20] de Franchis R. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepato,2015,63: 743-752. [21] Baeyens N, Bandyopadhyay C, Coon BG, et al. Endothelial fluid shear stress sensing in vascular health and disease. J Clin Invest,2016,126: 821-828. [22] Cartin-Ceba R, Krowka MJ. Portopulmonary hypertension. Clin Liver Dis,2014,18: 421-438. [23] Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology,2008,48: 2064-2077. [24] Park SC, Beerman LB, Gartner JC, et al. Echocardiographic findings before and after liver transplantation. Am J Cardiol,1985,55: 1373-1378. [25] Elisabeth Miot-Noirault LF, Yves Guichard JM, Pape AL. Scintigraphic in vivo assessment of the development of pulmonary intravascular macrophages in liver disease: experimental study in rats with biliary cirrhosis. CHEST,2001,120: 941-947. [26] Nunes H, Lebrec D, Mazmanian M, et al. Role of nitric oxide in hepatopulmonary syndrome in cirrhotic rats. Am J Respir Crit Care Med,2001,164:879-885. [27] Pellicelli AM, Barbaro G, Puoti C,?et al. Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation. ANGIOLOGY,2010,61:802-806. [28] Turco L, Garcia-Tsao G, Magnani I, et al. Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis. J Hepatol,?2018, 68:949-958. [29] 殷鑫. 肝硬化并发门脉性肺动脉高压患者的临床特征分析. 吉林大学,2020. [30] Lane KB, Machado RD, Pauciulo MW, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet,2000,26: 81-84. [31] Desroches-Castan A, Tillet E, Ricard N, et al. Bone Morphogenetic Protein 9 Is a Paracrine Factor Controlling Liver Sinusoidal Endothelial Cell Fenestration and Protecting Against Hepatic Fibrosis. Hepatology,2019,70: 1392-1408. [32] Rochon ER, Krowka MJ, Bartolome S, et al. BMP 9/10 in Pulmonary Vascular Complications of Liver Disease. Am J Resp Crit Care, 2020,201. [33] Long L, Ormiston ML, Yang X, et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med,2015,21:777-785.. [34] Kawut SM, Krowka MJ, Trotter JF, et al. Clinical risk factors for portopulmonary hypertension. Hepatology,2008,48: 196-203. [35] Chen H, Wang F, Xiao J, et al. Natural killer cell-mediated immune deficiency or compromise in patients with portopulmonary hypertension. Arch Med Sci,2014,10: 1055-1056. [36] Koksal D, Koksal AS, Gurakar A. Pulmonary Manifestations among Patients with Primary Biliary Cirrhosis. J Clin Transl Hepatol.2016,4:258-262. [37] Terao M, Takaki A, Maruyama T, et al. Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study. Intern Med,2015,54:2815-2826. [38] 刘以俊, 李涛. 《2016年国际肝移植学会实践指南:肝肺综合征与门脉性肺动脉高压的诊断与管理》摘译. 临床肝胆病杂志,2016,32: 1838-1842. [39] Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J,2019,53:1801913. [40] Colle IO, Moreau R, Godinho E, et al. Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. Hepatology,2003, 37: 401-409. [41] Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Rev Esp Cardiol (Engl Ed),2016,69:177. [42] Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. New Engl J Med,2013,369: 809-818. [43] Sidharta PN, Lindegger N, Ul I, et al. Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in subjects with hepatic or renal impairment.J Clin Pharmacol,2014,54:291-300. [44] Preston IR, Burger CD, Bartolome S, et al. Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial - ScienceDirect. J Heart Lung Transplant,2020,39:464-472. [45] 徐杰, 史阳阳, 孙凯. 门脉性肺动脉高压发病机制及治疗的最新研究进展. 医学综述,2021,27: 2503-2508. [46] Cartin-Ceba R, Halank M, Ghofrani HA, et al. Riociguat treatment for portopulmonary hypertension: a subgroup analysis from the PATENT-1/-2 studies. Pulm Circ, 2018, 8:2045894018769305. [47] Krowka MJ, Plevak DJ, Findlay JY, et al. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl,2000,6:443-450. [48] Savale L, Sattler C, Coilly A, et al. Long-term outcome in liver transplantation candidates with portopulmonary hypertension. Hepatology (Baltimore, Md.). 2017. [49] Bandara M, Gordon FD, Sarwar A, et al. Successful outcomes following living donor liver transplantation for portopulmonary hypertension. Hepatology,2017,65:1683-1692. [50] Grannas G, Neipp M, Hoeper MM, et al. Indications for and outcomes after combined lung and liver transplantation: a single-center experience on 13 consecutive cases. Transplantation, 2008, 85: 524-531. |
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