风湿性疾病与门静脉高压
DOI: 10.12449/JCH250503
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:申梨负责课题设计,资料分析,撰写论文;段维佳、吕婷婷参与收集数据,修改论文;贾继东负责拟定写作思路,指导撰写文章并最后定稿。
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摘要: 风湿性疾病是一类以免疫系统异常为特征的慢性疾病,而门静脉高压则发生于各种原因所致的门静脉系统血流增多或阻力增加,或肝静脉系统回流受阻。风湿性疾病及其治疗药物均可导致非肝硬化性门静脉高压。风湿性疾病相关的高凝状态可导致门静脉及肝静脉系统血栓形成,肝内门静脉系统和肝窦内皮系统的损伤可导致门脉肝窦血管病及肝窦阻塞综合征。治疗风湿性疾病的药物也可通过肝实质损伤导致肝纤维化及肝硬化,或通过对肝脏血管内皮的损伤导致非肝硬化性门静脉高压。本文将重点介绍常见的风湿性疾病及其治疗药物导致门静脉高压的机制及特点,旨在为其临床诊治及随访监测提供思路和帮助。Abstract: Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system, while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow. Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension. The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems, and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome. Moreover, drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury, which further leads to liver fibrosis and cirrhosis, or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension. This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension, in order to provide insights and assistance for clinical diagnosis, treatment, and follow-up monitoring.
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Key words:
- Rheumatic Diseases /
- Portal Hypertension /
- Diagnosis
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[1] KHANNA R, SARIN SK. Noncirrhotic portal hypertension: Current and emerging perspectives[J]. Clin Liver Dis, 2019, 23( 4): 781- 807. DOI: 10.1016/j.cld.2019.07.006. [2] HE FL, JIA JD. Research advances in porto-sinusoidal vascular disease[J]. J Clin Hepatol, 2024, 40( 1): 19- 23. DOI: 10.12449/JCH240103.何福亮, 贾继东. 门脉肝窦血管病的研究进展[J]. 临床肝胆病杂志, 2024, 40( 1): 19- 23. DOI: 10.12449/JCH240103. [3] WANLESS IR. Micronodular transformation(nodular regenerative hyperplasia) of the liver: A report of 64 cases among 2, 500 autopsies and a new classification of benign hepatocellular nodules[J]. Hepatology, 1990, 11( 5): 787- 797. DOI: 10.1002/hep.1840110512. [4] TONUTTI A, PUGLIESE N, CERIBELLI A, et al. The autoimmune landscape of Porto-sinusoidal vascular disorder: What the rheumatologist needs to know[J]. Semin Arthritis Rheum, 2024, 67: 152467. DOI: 10.1016/j.semarthrit.2024.152467. [5] CERDA REYES E, GONZÁLEZ-NAVARRO EA, MAGAZ M, et al. Autoimmune biomarkers in Porto-sinusoidal vascular disease: Potential role in its diagnosis and pathophysiology[J]. Liver Int, 2021, 41( 9): 2171- 2178. DOI: 10.1111/liv.14997. [6] MATSUMOTO T, KOBAYASHI S, SHIMIZU H, et al. The liver in collagen diseases: Pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver[J]. Liver, 2000, 20( 5): 366- 373. DOI: 10.1034/j.1600-0676.2000.020005366.x. [7] GORITSAS C, ROUSSOS A, FERTI A, et al. Nodular regenerative hyperplasia in a rheumatoid arthritis patient without Felty’s syndrome[J]. J Clin Gastroenterol, 2002, 35( 4): 363- 364. DOI: 10.1097/00004836-200210000-00020. [8] YANG S, QUAN M, LI Y, et al. Porto-sinusoidal vascular disease as the cause of portal hypertension in Felty’s syndrome: A case report and literature review[J]. Biomed Res Int, 2020, 2020: 2618260. DOI: 10.1155/2020/2618260. [9] ROSENSTEIN ED, KRAMER N. Felty’s and Pseudo-Felty’s syndromes[J]. Semin Arthritis Rheum, 1991, 21( 3): 129- 142. DOI: 10.1016/0049-0172(91)90002-h. [10] STOCK H, KADRY Z, SMITH JP. Surgical management of portal hypertension in Felty’s syndrome: A case report and literature review[J]. J Hepatol, 2009, 50( 4): 831- 835. DOI: 10.1016/j.jhep.2008.10.035. [11] NOBLE S, LINZ M, CORREIA E, et al. Porto-sinusoidal vascular disease and portal hypertension[J]. Clin Liver Dis, 2024, 28( 3): 455- 466. DOI: 10.1016/j.cld.2024.03.004. [12] AFZAL W, HAGHI M, HASNI SA, et al. Lupus hepatitis, more than just elevated liver enzymes[J]. Scand J Rheumatol, 2020, 49( 6): 427- 433. DOI: 10.1080/03009742.2020.1744712. [13] SOLELA G, DABA M. Budd-Chiari syndrome as an initial presentation of systemic lupus erythematosus associated with antiphospholipid syndrome: A case report with review of the literature[J]. Open Access Rheumatol, 2023, 15: 139- 143. DOI: 10.2147/OARRR.S425535. [14] IMABAYASHI K, NAKANO K, IWATA S, et al. A case of systemic lupus erythematosus with marked ascites due to idiopathic non-cirrhotic portal hypertension[J]. Mod Rheumatol Case Rep, 2021, 5( 2): 285- 291. DOI: 10.1080/24725625.2021.1904607. [15] MATSUMOTO T, YOSHIMINE T, SHIMOUCHI K, et al. The liver in systemic lupus erythematosus: Pathologic analysis of 52 cases and review of Japanese Autopsy Registry Data[J]. Hum Pathol, 1992, 23( 10): 1151- 1158. DOI: 10.1016/0046-8177(92)90033-y. [16] YANG QB, HE YL, PENG CM, et al. Systemic lupus erythematosus complicated by noncirrhotic portal hypertension: A case report and review of literature[J]. World J Clin Cases, 2018, 6( 13): 688- 693. DOI: 10.12998/wjcc.v6.i13.688. [17] BESSONE F, POLES N, ROMA MG. Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis[J]. World J Hepatol, 2014, 6( 6): 394- 409. DOI: 10.4254/wjh.v6.i6.394. [18] SUÁREZ-DÍAZ S, GARCÍA-CALONGE M, MENDOZA-PACAS G, et al. Non-cirrhotic portal hypertension in systemic lupus erythematosus[J]. Cureus, 2023, 15( 2): e35494. DOI: 10.7759/cureus.35494. [19] YOU HX, ZHAO JL, HUANG C, et al. Early initiation of anticoagulation improves the long-term prognosis in patients with antiphospholipid syndrome associated portal vein thrombosis[J]. Front Med(Lausanne), 2021, 8: 630660. DOI: 10.3389/fmed.2021.630660. [20] PENGO V, RUFFATTI A, LEGNANI C, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome[J]. J Thromb Haemost, 2010, 8( 2): 237- 242. DOI: 10.1111/j.1538-7836.2009.03674.x. [21] KLEIN R, GOLLER S, BIANCHI L. Nodular regenerative hyperplasia(NRH) of the liver-a manifestation of‘organ-specific antiphospholipid syndrome’?[J]. Immunobiology, 2003, 207( 1): 51- 57. DOI: 10.1078/0171-2985-00209. [22] MERONI PL, BORGHI MO, RASCHI E, et al. Pathogenesis of antiphospholipid syndrome: Understanding the antibodies[J]. Nat Rev Rheumatol, 2011, 7( 6): 330- 339. DOI: 10.1038/nrrheum.2011.52. [23] GIANNAKOPOULOS B, KRILIS SA. The pathogenesis of the antiphospholipid syndrome[J]. N Engl J Med, 2013, 368( 11): 1033- 1044. DOI: 10.1056/NEJMra1112830. [24] YAMAMOTO A, MATSUDA H, HIRAMATSU K, et al. A case of idiopathic portal hypertension accompanying multiple hepatic nodular regenerative hyperplasia in a patient with systemic sclerosis[J]. Clin J Gastroenterol, 2021, 14( 3): 820- 826. DOI: 10.1007/s12328-021-01348-z. [25] TAKAGI K, NISHIO S, AKIMOTO K, et al. A case of systemic sclerosis complicated by idiopathic portal hypertension: Case report and literature review[J]. Mod Rheumatol, 2006, 16( 3): 183- 187. DOI: 10.1007/s10165-006-0479-1. [26] GRAF L, DOBROTA R, JORDAN S, et al. Nodular regenerative hyperplasia of the liver: A rare vascular complication in systemic sclerosis[J]. J Rheumatol, 2018, 45( 1): 103- 106. DOI: 10.3899/jrheum.170292. [27] SAIGUSA R, TOYAMA T, ICHIMURA Y, et al. A case of systemic sclerosis complicated with portal hypertension[J]. J Clin Rheumatol, 2021, 27( 8S): S668- S669. DOI: 10.1097/rhu.0000000000001633. [28] NAKAMURA M, KONDO H, MORI T, et al. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis[J]. Hepatology, 2007, 45( 1): 118- 127. DOI: 10.1002/hep.21472. [29] NAKANUMA Y, SATO Y, KIKTAO A. Pathology and pathogenesis of portal venopathy in idiopathic portal hypertension: Hints from systemic sclerosis[J]. Hepatol Res, 2009, 39( 10): 1023- 1031. DOI: 10.1111/j.1872-034X.2009.00555.x. [30] READ AE, WIESNER RH, LABRECQUE DR, et al. Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy[J]. Ann Intern Med, 1986, 104( 5): 651- 655. DOI: 10.7326/0003-4819-104-5-651. [31] EISENHAUER T, HARTMANN H, RUMPF KW, et al. Favourable outcome of hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine, treated by portacaval shunt. Report of a case and review of the literature[J]. Digestion, 1984, 30( 3): 185- 190. DOI: 10.1159/000199104. [32] LEMLEY DE, DELACY LM, SEEFF LB, et al. Azathioprine induced hepatic veno-occlusive disease in rheumatoid arthritis[J]. Ann Rheum Dis, 1989, 48( 4): 342- 346. DOI: 10.1136/ard.48.4.342. [33] PRAPROTNIK S, HOCEVAR A, FERLAN-MAROLT V, et al. Azathioprine induced hepatic veno-occlusive disease in systemic lupus erythematosus[J]. Lupus, 2005, 14( 6): 493- 494. DOI: 10.1191/0961203305lu2143xx. [34] MION F, NAPOLEON B, BERGER F, et al. Azathioprine induced liver disease: Nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis[J]. Gut, 1991, 32( 6): 715- 717. DOI: 10.1136/gut.32.6.715. [35] HOLTMANN M, SCHREINER O, KÖHLER H, et al. Veno-occlusive disease(VOD) in Crohn’s disease(CD) treated with azathioprine[J]. Dig Dis Sci, 2003, 48( 8): 1503- 1505. DOI: 10.1023/a:1024755521423. [36] DELEVE LD, WANG X, KUHLENKAMP JF, et al. Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease[J]. Hepatology, 1996, 23( 3): 589- 599. DOI: 10.1002/hep.510230326. [37] BAYOUMY AB, SIMSEK M, SEINEN ML, et al. The continuous rediscovery and the benefit-risk ratio of thioguanine, a comprehensive review[J]. Expert Opin Drug Metab Toxicol, 2020, 16( 2): 111- 123. DOI: 10.1080/17425255.2020.1719996. [38] de BOER NKH, van BODEGRAVEN AA, JHARAP B, et al. Drug Insight: Pharmacology and toxicity of thiopurine therapy in patients with IBD[J]. Nat Clin Pract Gastroenterol Hepatol, 2007, 4( 12): 686- 694. DOI: 10.1038/ncpgasthep1000. [39] de BOER NK, MULDER CJ, van BODEGRAVEN AA. Nodular regenerative hyperplasia and thiopurines: the case for level-dependent toxicity[J]. Liver Transpl, 2005, 11( 10): 1300- 1301. DOI: 10.1002/lt.20554. [40] DUBINSKY MC, VASILIAUSKAS EA, SINGH H, et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients[J]. Gastroenterology, 2003, 125( 2): 298- 303. DOI: 10.1016/s0016-5085(03)00938-7. [41] de BOER NK, ZONDERVAN PE, GILISSEN LP, et al. Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients[J]. Dig Liver Dis, 2008, 40( 2): 108- 113. DOI: 10.1016/j.dld.2007.10.013. [42] GILISSEN LP, DERIJKS LJ, DRIESSEN A, et al. Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?[J]. Dig Liver Dis, 2007, 39( 2): 156- 159. DOI: 10.1016/j.dld.2006.10.007. [43] BAFNA P, SAHOO RR, HAZARIKA K, et al. Prevalence of liver fibrosis by Fibroscan in patients on long-term methotrexate therapy for rheumatoid arthritis[J]. Clin Rheumatol, 2021, 40( 9): 3605- 3613. DOI: 10.1007/s10067-021-05678-8. [44] RUIZ-PONCE M, CUESTA-LÓPEZ L, LÓPEZ-MONTILLA MD, et al. Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses[J]. Biomed Pharmacother, 2023, 168: 115779. DOI: 10.1016/j.biopha.2023.115779. [45] di MARTINO V. Methotrexate-induced liver fibrosis: The end of a long-held belief[J]. J Hepatol, 2023, 78( 5): 896- 897. DOI: 10.1016/j.jhep.2023.02.018. [46] MORI S, ARIMA N, ITO M, et al. Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment[J]. PLoS One, 2018, 13( 8): e0203084. DOI: 10.1371/journal.pone.0203084. [47] ATALLAH E, GROVE JI, CROOKS C, et al. Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated[J]. J Hepatol, 2023, 78( 5): 989- 997. DOI: 10.1016/j.jhep.2022.12.034. [48] DI MARTINO V, VERHOEVEN DW, VERHOEVEN F, et al. Busting the myth of methotrexate chronic hepatotoxicity[J]. Nat Rev Rheumatol, 2023, 19( 2): 96- 110. DOI: 10.1038/s41584-022-00883-4. [49] ALCORN N, SAUNDERS S, MADHOK R. Benefit-risk assessment of leflunomide: An appraisal of leflunomide in rheumatoid arthritis 10 years after licensing[J]. Drug Saf, 2009, 32( 12): 1123- 1134. DOI: 10.2165/11316650-000000000-00000. [50] LEE SW, PARK HJ, KIM BK, et al. Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate[J]. Arthritis Res Ther, 2012, 14( 5): R232. DOI: 10.1186/ar4075. [51] AVOUAC J, DEGRAVE R, VERGNEAULT H, et al. Risk of liver fibrosis induced by methotrexate and other rheumatoid arthritis medications according to the Fibrosis-4 Index[J]. Clin Exp Rheumatol, 2022, 40( 1): 150- 157. DOI: 10.55563/clinexprheumatol/usddjr. [52] BILASY SE, ESSAWY SS, MANDOUR MF, et al. Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate combination in a rat model of rheumatoid arthritis[J]. Pharmacol Rep, 2015, 67( 1): 102- 114. DOI: 10.1016/j.pharep.2014.08.009. [53] ELSHAER RE, TAWFIK MK, NOSSEIR N, et al. Leflunomide-induced liver injury in mice: Involvement of TLR4 mediated activation of PI3K/mTOR/NFκB pathway[J]. Life Sci, 2019, 235: 116824. DOI: 10.1016/j.lfs.2019.116824. -

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