风湿性疾病肝脏受累的诊断与治疗

阙子媛; 孟繁星; 刘春桐; 刘燕鹰; 齐海宇

doi:10.12449/JCH250502

风湿性疾病肝脏受累的诊断与治疗

DOI: 10.12449/JCH250502

首都医科大学附属北京友谊医院风湿科，北京 100050

基金项目:

北京自然科学基金面上项目 (7222039);

北京自然科学基金面上项目 (7232029)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：阙子媛负责资料分析，撰写论文；孟繁星、刘春桐参与查阅文献，修改论文；齐海宇、刘燕鹰负责课题设计，拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
齐海宇， qihaiyu789@126.com （ORCID： 0009-0009-2915-1615）

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出版历程
- 收稿日期: 2025-03-03
- 录用日期: 2025-04-07
- 出版日期: 2025-05-25

Diagnosis and treatment of liver involvement secondary to rheumatic diseases

Department of Rheumatology，Beijing Friendship Hospital，Capital Medical University，Beijing 100050，China

Research funding:

General Program of Beijing Natural Science Foundation (7222039);

General Program of Beijing Natural Science Foundation (7232029)

More Information

Corresponding author: QI Haiyu， qihaiyu789@126.com （ORCID： 0009-0009-2915-1615）

摘要

摘要: 风湿性疾病是一类慢性、炎症性自身免疫性疾病，可累及多个器官及系统。临床中风湿病患者在病程中大多表现为无症状肝功能异常，病因与风湿性疾病本身、药物、代谢、病毒或合并其他慢性肝病有关。免疫介导的炎症反应在风湿病肝脏受累（包括肝细胞损伤、肝内血管病变、肝纤维化）中发挥重要作用。本文对风湿性疾病相关肝脏受累的临床特征及诊治要点进行探讨，以提高相关专科医生对该病的认识。
- 风湿性疾病 /
- 肝脏受累 /
- 诊断 /
- 治疗学
Abstract: Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems. In clinical practice， most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease， and the etiology of such diseases may be associated with the rheumatic disease itself， medications， metabolism， viruses， or the presence of other chronic liver diseases. Immune-mediated inflammatory responses play a significant role in liver involvement （including hepatocyte injury， intrahepatic vascular lesions， and hepatic fibrosis） in rheumatic diseases. This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases， in order to enhance the understanding of this condition among specialists in related fields.
- Rheumatic Diseases /
- Liver Involvement /
- Diagnosis /
- Therapeutics

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参考文献(45)

[1]	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.
[2]	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.
[3]	PIGA M, VACCA A, PORRU G, et al. Liver involvement in systemic lupus erythematosus: Incidence, clinical course and outcome of lupus hepatitis[J]. Clin Exp Rheumatol, 2010, 28( 4): 504- 510.
[4]	ZHANG XY, ZHANG YX, WANG ZQ, et al. Study of 43 SLE patients with autoimmune liver cirrhosis: Emphasis on clinical features and differences from lupus without cirrhosis[J]. Int J Rheum Dis, 2023, 26( 7): 1268- 1275. DOI: 10.1111/1756-185X.14712.
[5]	ADIGA A, NUGENT K. Lupus hepatitis and autoimmune hepatitis(lupoid hepatitis)[J].‍ Am J Med Sci, 2017, ‍ 353( 4): 329- 335. ‍ DOI: ‍10.1016/j.amjms.2016.10.014.
[6]	GEZER S. Antiphospholipid syndrome[J]. Dis Mon, 2003, 49( 12): 696- 741. DOI: 10.1016/j.disamonth.2003.10.001.
[7]	TAGAWA Y, SAITO T, TAKADA K, et al. Successful treatment of severe refractory lupus hepatitis with mycophenolate mofetil[J]. Lupus, 2016, 25( 5): 543- 546. DOI: 10.1177/0961203315625118.
[8]	FAN QY, JI HY, LIU Y, et al. Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review[J]. Lupus, 2024, 33( 4): 414- 419. DOI: 10.1177/09612033241233021.
[9]	ARIAS-DE LA ROSA I, RUIZ-PONCE M, CUESTA-LÓPEZ L, et al. Clinical features and immune mechanisms directly linked to the altered liver function in patients with rheumatoid arthritis[J]. Eur J Intern Med, 2023, 118: 49- 58. DOI: 10.1016/j.ejim.2023.08.002.
[10]	ZHANG SP, ZHU P, YUAN JN, et al. Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats[J]. Front Pharmacol, 2023, 14: 1149665. DOI: 10.3389/fphar.2023.1149665.
[11]	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.
[12]	EBERT EC, HAGSPIEL KD. Gastrointestinal and hepatic manifestations of rheumatoid arthritis[J]. Dig Dis Sci, 2011, 56( 2): 295- 302. DOI: 10.1007/s10620-010-1508-7.
[13]	ZAMANI M, ALIZADEH-TABARI S, CHITKARA P, et al. Prevalence of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A systematic review and meta-analysis[J]. Clin Gastroenterol Hepatol, 2023, 21( 11): 2789- 2796. DOI: 10.1016/j.cgh.2023.02.021.
[14]	ORTOLAN A, LORENZIN M, TADIOTTO G, et al. Metabolic syndrome, non-alcoholic fatty liver disease and liver stiffness in psoriatic arthritis and psoriasis patients[J]. Clin Rheumatol, 2019, 38( 10): 2843- 2850. DOI: 10.1007/s10067-019-04646-7.
[15]	VASSILOPOULOS A, KALLIGEROS M, VASSILOPOULOS S, et al. Prevalence of steatotic liver disease among US adults with rheumatoid arthritis[J]. Dig Dis Sci, 2024, 69( 3): 989- 1003. DOI: 10.1007/s10620-023-08225-4.
[16]	RETAMOZO S, BALDINI C, BOOTSMA H, et al. Therapeutic recommendations for the management of older adult patients with Sjögren’s syndrome[J]. Drugs Aging, 2021, 38( 4): 265- 284. DOI: 10.1007/s40266-021-00838-6.
[17]	MENG YH, CHEN YF, ZHOU PR. Clinical and immunological features of primary Sjögren’s syndrome patients with positive anti-centromere protein B antibody[J]. J Peking Univ(Health Sci), 2023, 55( 6): 1088- 1096. DOI: 10.19723/j.issn.1671-167X.2023.06.021. 孟彦宏, 陈怡帆, 周培茹. CENP-B抗体阳性的原发性干燥综合征患者的临床和免疫学特征[J]. 北京大学学报(医学版), 2023, 55( 6): 1088- 1096. DOI: 10.19723/j.issn.1671-167X.2023.06.021.
[18]	LIU YX, GUO LX, LIN W, et al. Anticentromere antibody positive patients with primary Sjögren’s syndrome have distinctive clinical and immunological characteristics[J]. Clin Exp Rheumatol, 2023, 41( 12): 2371- 2378. DOI: 10.55563/clinexprheumatol/o3pxq0.
[19]	ANDROUTSAKOS T, VOULGARIS TA, BAKASIS AD, et al. Liver fibrosis in primary Sjögren’s syndrome[J]. Front Immunol, 2022, 13: 889021. DOI: 10.3389/fimmu.2022.889021.
[20]	ZHANG MJ, ZHANG S. T cells in fibrosis and fibrotic diseases[J]. Front Immunol, 2020, 11: 1142. DOI: 10.3389/fimmu.2020.01142.
[21]	DENTON CP, KHANNA D. Systemic sclerosis[J]. Lancet, 2017, 390( 10103): 1685- 1699. DOI: 10.1016/s0140-6736(17)30933-9.
[22]	UTIYAMA SR, ZENATTI KB, NÓBREGA HA, et al. Rheumatic disease autoantibodies in autoimmune liver diseases[J]. Immunol Invest, 2016, 45( 6): 566- 573. DOI: 10.1080/08820139.2016.1186173.
[23]	SAWADPANICH K, PROMASEN P, MAIRIANG P, et al. Incidence and predictors of an abnormal liver function test among 674 systemic sclerosis patients: A cohort study[J]. Open Access Rheumatol, 2023, 15: 81- 92. DOI: 10.2147/OARRR.S410165.
[24]	LORENA M, BELLAN M, LEPORE M, et al. Clinical relevance of liver involvement in the clinical course of systemic sclerosis[J]. J Clin Med, 2022, 11( 4): 966. DOI: 10.3390/jcm11040966.
[25]	EBERT EC, HAGSPIEL KD, NAGAR M, et al. Gastrointestinal involvement in polyarteritis nodosa[J]. Clin Gastroenterol Hepatol, 2008, 6( 9): 960- 966. DOI: 10.1016/j.cgh.2008.04.004.
[26]	SANSONNO D, DAMMACCO F. Hepatitis C virus, cryoglobulinaemia, and vasculitis: Immune complex relations[J]. Lancet Infect Dis, 2005, 5( 4): 227- 236. DOI: 10.1016/S1473-3099(05)70053-0.
[27]	ANDERSON E, GAKHAR N, STULL C, et al. Gastrointestinal and hepatic disease in vasculitis[J]. Rheum Dis Clin North Am, 2018, 44( 1): 1- 14. DOI: 10.1016/j.rdc.2017.09.001.
[28]	UCHIDA T, FUKUI S, IWAMOTO N, et al. Absence of glucocorticoids concomitant with avacopan and subsequent liver injury in antineutrophil cytoplasmic antibody-associated vasculitis[J]. J Rheumatol, 2024, 51( 11): 1146- 1148. DOI: 10.3899/jrheum.2024-0340.
[29]	MATHUR T, MANADAN AM, THIAGARAJAN S, et al. Serum transaminases are frequently elevated at time of diagnosis of idiopathic inflammatory myopathy and normalize with creatine kinase[J]. J Clin Rheumatol, 2014, 20( 3): 130- 132. DOI: 10.1097/RHU.0000000000000038.
[30]	LANIS A, VOLOCHAYEV R, KLEINER DE, et al. Nodular regenerative hyperplasia of the liver in juvenile dermatomyositis[J]. Pediatr Rheumatol Online J, 2022, 20( 1): 30. DOI: 10.1186/s12969-022-00690-x.
[31]	NAGASHIMA T, KAMATA Y, IWAMOTO M, et al. Liver dysfunction in anti-melanoma differentiation-associated gene 5 antibody-positive patients with dermatomyositis[J]. Rheumatol Int, 2019, 39( 5): 901- 909. DOI: 10.1007/s00296-019-04255-2.
[32]	YANG X, CUI XG, YANG X, et al. Liver involvement is associated with higher risk of rapidly progressive interstitial lung disease and mortality in anti-melanoma differentiation-associated gene 5 antibody- positive dermatomyositis[J]. J Inflamm Res, 2024, 17: 3101- 3113. DOI: 10.2147/JIR.S462721.
[33]	HOSOYA S, SADATSUKI M, IZUKA S, et al. A case of recurrence of adult-onset Still’s disease in the third trimester: A case report and literature review[J]. BMC Pregnancy Childbirth, 2021, 21( 1): 163. DOI: 10.1186/s12884-021-03648-1.
[34]	JIA JC, WANG MY, MENG JF, et al. Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still’s disease pathogenesis[J]. Nat Commun, 2022, 13( 1): 6804. DOI: 10.1038/s41467-022-34560-7.
[35]	LI X, DONG CN, MA XW, et al. ¹⁸F-FDG PET/CT associates with disease activity and clinical recurrence of AOSD patients[J]. Front Med(Lausanne), 2021, 8: 668323. DOI: 10.3389/fmed.2021.668323.
[36]	CHI HH, WANG ZH, MENG JF, et al. A cohort study of liver involvement in patients with adult-onset Still’s disease: Prevalence, characteristics and impact on prognosis[J]. Front Med(Lausanne), 2020, 7: 621005. DOI: 10.3389/fmed.2020.621005.
[37]	MYLONA E, GOLFINOPOULOU S, SAMARKOS M, et al. Acute hepatitis in adult Still’s disease during corticosteroid treatment successfully treated with anakinra[J]. Clin Rheumatol, 2008, 27( 5): 659- 661. DOI: 10.1007/s10067-007-0791-y.
[38]	MULLER R, BRIANTAIS A, FAUCHER B, et al. Acute severe hepatitis in adult-onset Still’s disease: Case report and comprehensive review of a life-threatening manifestation[J]. Clin Rheumatol, 2021, 40( 6): 2467- 2476. DOI: 10.1007/s10067-020-05383-y.
[39]	TAYLOR SA, VITTORIO JM, MARTINEZ M, et al. Anakinra-induced acute liver failure in an adolescent patient with Still’s disease[J]. Pharmacotherapy, 2016, 36( 1): e1- e4. DOI: 10.1002/phar.1677.
[40]	TANAKA A, NOTOHARA K. Immunoglobulin G4(IgG4)-related autoimmune hepatitis and IgG4-hepatopathy: A histopathological and clinical perspective[J]. Hepatol Res, 2021, 51( 8): 850- 859. DOI: 10.1111/hepr.13683.
[41]	LANZILLOTTA M, CULVER E, SHARMA A, et al. Fibrotic phenotype of IgG4-related disease[J]. Lancet Rheumatol, 2024, 6( 7): e469- e480. DOI: 10.1016/S2665-9913(23)00299-0.
[42]	BECQ A, CAMUS M, ARRIVÉ L, et al. IgG4-related sclerosing cholangitis presenting as an isolated intrahepatic stenosis: A rare presentation of a rare disease[J]. Endoscopy, 2021, 53( 6): E205- E206. DOI: 10.1055/a-1244-9065.
[43]	LIN H, LIU Y, WEI YY, et al. Characteristics of imaging in hepatic inflammatory pseudotumors: A comparison between IgG4-related and IgG4-unrelated cases[J]. Insights Imaging, 2024, 15( 1): 203. DOI: 10.1186/s13244-024-01782-w.
[44]	WANG TQ, LIU YY. Advances in diagnosis and treatment of IgG4-related hepatobiliary and pancreatic diseases[J]. J Clin Hepatol, 2022, 38( 4): 762- 766. DOI: 10.3969/j.issn.1001-5256.2022.04.006. 王天琪, 刘燕鹰. IgG4相关肝胆胰疾病诊疗进展[J]. 临床肝胆病杂志, 2022, 38( 4): 762- 766. DOI: 10.3969/j.issn.1001-5256.2022.04.006.
[45]	LUO YP, PAN QQ, YANG HX, et al. Fibroblast activation protein-targeted PET/CT with ⁶⁸Ga-FAPI for imaging IgG4-related disease: Comparison to ¹⁸F-FDG PET/CT[J]. J Nucl Med, 2021, 62( 2): 266- 271. DOI: 10.2967/jnumed.120.244723.