儿童风湿病与肝脏病变

孙菲; 毛华伟

doi:10.12449/JCH250505

儿童风湿病与肝脏病变

DOI: 10.12449/JCH250505

孙菲,
毛华伟^, ,

国家儿童医学中心，首都医科大学附属北京儿童医院免疫科，北京 100045

基金项目:

国家重点研发计划 (2021YFC2702005);

北京市医院管理中心临床医学发展专项 (ZLRK202527);

北京市医院管理中心“登峰”计划专项 (DFL20221001)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：孙菲负责资料分析，收集数据，撰写论文；毛华伟负责课题设计，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:
毛华伟， maohwei@qq.com （ORCID： 0000-0001-8807-9267）

计量
- 文章访问数: 1323
- HTML全文浏览量: 35
- PDF下载量: 18
- 被引次数: 0
出版历程
- 收稿日期: 2025-03-10
- 录用日期: 2025-04-07
- 出版日期: 2025-05-25

Liver involvement in pediatric rheumatic diseases

Fei SUN,
Huawei MAO^{,
,}

Department of Immunology，Beijing Children’s Hospital，Capital Medical University，National Center for Children’s Health，Beijing 100045，China

Research funding:

National Key R&D Program of China (2021YFC2702005);

Beijing Hospitals Authority Clinical Medicine Development of Special Funding (ZLRK202527);

Beijing Hospitals Authority’s Ascent Plan (DFL20221001)

More Information

Corresponding author: MAO Huawei， maohwei@qq.com （ORCID： 0000-0001-8807-9267）

摘要

摘要: 儿童风湿病是一组复杂的慢性炎症性疾病，主要包括幼年型特发性关节炎、弥漫性结缔组织病、系统性血管炎和自身炎症性疾病等。儿童风湿病合并肝脏病变较为常见，多数仅表现为不同程度的肝酶异常或肝肿大，可能不伴有显著的肝实质病变，且很少进展至肝功能失代偿期。极少数风湿病患儿可能出现严重的肝脏病变。儿童风湿病出现肝脏病变的病因可能是原发病本身引起，也可能是合并自身免疫性肝病所致，但更常见于治疗风湿病药物所致的药物性肝损伤、合并病毒性肝炎或脂肪肝等其他继发性因素。本文总结了常见的儿童风湿病合并肝脏病变，旨在为临床诊疗过程中的病因分析、诊断和治疗策略提供参考。
- 风湿性疾病 /
- 肝脏受累 /
- 儿童
Abstract: Pediatric rheumatic diseases are a group of complex chronic inflammatory disorders， mainly including juvenile idiopathic arthritis， diffuse connective tissue diseases， systemic vasculitis， and autoinflammatory diseases. Liver involvement is quite common in pediatric rheumatic diseases. In most cases， pediatric rheumatic diseases with liver involvement manifest as varying degrees of abnormal liver enzymes or hepatomegaly and may not have significant liver parenchyma lesions， and such diseases rarely progress to liver decompensation. Only a few children with rheumatic diseases may develop severe liver lesions. Liver involvement in children with rheumatic diseases may be caused by the primary disease itself or concurrent autoimmune liver diseases， but secondary factors are more common， including drug-induced liver damage caused by drugs used to treat rheumatic diseases， viral hepatitis， and fatty liver disease. This article summarizes liver involvement in pediatric rheumatic diseases， in order to provide a reference for the etiological analysis， diagnosis， and treatment strategies of liver involvement in pediatric rheumatic diseases.
- Rheumatic Diseases /
- Liver Involvement /
- Child

HTML全文

参考文献(46)

[1]	SCHALLER J, BECKWITH B, WEDGWOOD RJ. Hepatic involvement in juvenile rheumatoid arthritis[J]. 1970, 77( 2): 203- 210. DOI: 10.1016/s0022-3476(70)80324-9.
[2]	GIRALDO WAS, MORATILLA AB, CAPARRÓS AM, et al. Nodular regenerative hyperplasia of the liver as a complication of long-standing systemic-onset juvenile idiopathic arthritis[J]. Reumatol Clin, 2014, 10( 3): 194- 195. DOI: 10.1016/j.reuma.2013.09.001.
[3]	CANNA S, FRANKOVICH J, HIGGINS G, et al. Acute hepatitis in three patients with systemic juvenile idiopathic arthritis taking interleukin-1 receptor antagonist[J]. Pediatr Rheumatol Online J, 2009, 7: 21. DOI: 10.1186/1546-0096-7-21.
[4]	RUPERTO N, BRUNNER HI, QUARTIER P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis[J]. N Engl J Med, 2012, 367( 25): 2396- 2406. DOI: 10.1056/NEJMoa1205099.
[5]	GENOVESE MC, KREMER JM, van VOLLENHOVEN RF, et al. Transaminase levels and hepatic events during tocilizumab treatment: Pooled analysis of long-term clinical trial safety data in rheumatoid arthritis[J]. Arthritis Rheumatol, 2017, 69( 9): 1751- 1761. DOI: 10.1002/art.40176.
[6]	MINOIA F, DAVÌ S, HORNE A, et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: A multinational, multicenter study of 362 patients[J]. Arthritis Rheumatol, 2014, 66( 11): 3160- 3169. DOI: 10.1002/art.38802.
[7]	FAUTREL B, MITROVIC S, DE MATTEIS A, et al. EULAR/PReS recommendations for the diagnosis and management of Still’s disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still’s disease[J]. Ann Rheum Dis, 2024, 83( 12): 1614- 1627. DOI: 10.1136/ard-2024-225851.
[8]	IRVING KS, SEN D, TAHIR H, et al. A comparison of autoimmune liver disease in juvenile and adult populations with systemic lupus erythematosus-a retrospective review of cases[J]. Rheumatology(Oxford), 2007, 46( 7): 1171- 1173. DOI: 10.1093/rheumatology/kem108.
[9]	TAKAHASHI A, ABE K, SAITO R, et al. Liver dysfunction in patients with systemic lupus erythematosus[J]. Intern Med, 2013, 52( 13): 1461- 1465. DOI: 10.2169/internalmedicine.52.9458.
[10]	TAHERNIA L, ALIMADADI H, TAHGHIGHI F, et al. Frequency and type of hepatic and gastrointestinal involvement in juvenile systemic lupus erythematosus[J]. Autoimmune Dis, 2017, 2017: 8097273. DOI: 10.1155/2017/8097273.
[11]	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.
[12]	TRAPANI S, RUBINO C, SIMONINI G, et al. Gastrointestinal and hepatic involvement in paediatric systemic lupus erythematosus[J]. Clin Exp Rheumatol, 2021, 39( 4): 899- 906. DOI: 10.55563/clinexprheumatol/oebrcq.
[13]	EL-SHABRAWI MH, FARRAG MI. Hepatic manifestations in juvenile systemic lupus erythematosus[J]. Recent Pat Inflamm Allergy Drug Discov, 2014, 8( 1): 36- 40. DOI: 10.2174/1872213x07666131229110501.
[14]	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.
[15]	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.
[16]	DEEN MJ, PORTA G, FIOROT FJ, et al. Autoimmune hepatitis and juvenile systemic lupus erythematosus[J]. Lupus, 2009, 18( 8): 747- 751. DOI: 10.1177/0961203308100559.
[17]	BALBI VA, MONTENEGRO B, PITTA AC, et al. Autoimmune hepatitis in 847 childhood-onset systemic lupus erythematosus population: A multicentric cohort study[J]. Adv Rheumatol, 2018, 58( 1): 43. DOI: 10.1186/s42358-018-0043-7.
[18]	PAWŁOWSKA J, NAORNIAKOWSKA M, LIBER A. Liver involvement in children with collagen vascular diseases[J]. Clin Exp Hepatol, 2015, 1( 3): 117- 119. DOI: 10.5114/ceh.2015.55569.
[19]	GRYKA-MARTON M, SZUKIEWICZ D, TELIGA-CZAJKOWSKA J, et al. An overview of neonatal lupus with anti-ro characteristics[J]. Int J Mol Sci, 2021, 22( 17): 9281. DOI: 10.3390/ijms22179281.
[20]	DERDULSKA JM, RUDNICKA L, SZYKUT-BADACZEWSKA A, et al. Neonatal lupus erythematosus-practical guidelines[J]. J Perinat Med, 2021, 49( 5): 529- 538. DOI: 10.1515/jpm-2020-0543.
[21]	RUSSO RA, KATSICAS MM, DÁVILA M, et al. Cholestasis in juvenile dermatomyositis: Report of three cases[J]. Arthritis Rheum, 2001, 44( 5): 1139- 1142.
[22]	KINKOR M, HAMEED S, KATS A, et al. 14-month-old female with anti-MDA5 juvenile dermatomyositis complicated by liver disease: A case report[J]. Pediatr Rheumatol Online J, 2024, 22( 1): 86. DOI: 10.1186/s12969-024-01021-y.
[23]	YI BY, MARRS J, SCHENKER R, et al. Elevated liver enzymes: Unusual presentation of anti-MDA5 antibody-associated juvenile dermatomyositis[J]. Clin Exp Rheumatol, 2024, 42( 2): 456- 457. DOI: 10.55563/clinexprheumatol/25znui.
[24]	RAMOS-CASALS M, ACAR-DENIZLI N, VISSINK A, et al. Childhood-onset of primary Sjögren’s syndrome: Phenotypic characterization at diagnosis of 158 children[J]. Rheumatology(Oxford), 2021, 60( 10): 4558- 4567. DOI: 10.1093/rheumatology/keab032.
[25]	GONG YN, LIU HM, LI GM, et al. Childhood-onset primary Sjögren’s syndrome in a tertiary center in China: Clinical features and outcome[J]. Pediatr Rheumatol Online J, 2023, 21( 1): 11. DOI: 10.1186/s12969-022-00779-3.
[26]	MARINO A, ROMANO M, GIANI T, et al. Childhood Sjogren’s syndrome: An Italian case series and a literature review-based cohort[J]. Semin Arthritis Rheum, 2021, 51( 4): 903- 910. DOI: 10.1016/j.semarthrit.2020.11.004.
[27]	KASHIWAGI Y, HATSUSHIKA T, TSUTSUMI N, et al. Gastrointestinal and liver lesions in primary childhood Sjögren syndrome[J]. Clin Rheumatol, 2017, 36( 6): 1433- 1435. DOI: 10.1007/s10067-017-3599-4.
[28]	GEBRESELASSIE A, ADULI F, HOWELL CD. Rheumatologic diseases and the liver[J]. Clin Liver Dis, 2019, 23( 2): 247- 261. DOI: 10.1016/j.cld.2018.12.007.
[29]	CHAO HC, KONG MS, LIN SJ. Hepatobiliary involvement of Henoch-Schönlein purpura in children[J]. Acta Paediatr Taiwan, 2000, 41( 2): 63- 68.
[30]	GATSELIS NK, STEFOS A, GIOTI C, et al. Primary biliary cirrhosis and Henoch-Schonlein purpura: Report of two cases and review of the literature[J]. Liver Int, 2007, 27( 2): 280- 283. DOI: 10.1111/j.1478-3231.2006.01402.x.
[31]	REN YF, ZHANG CX, XU XQ, et al. A case report of atypical Kawasaki disease presented with severe elevated transaminases and literature review[J]. BMC Infect Dis, 2021, 21( 1): 415. DOI: 10.1186/s12879-021-06101-y.
[32]	MORITA A, IMAGAWA K, ISHIODORI T, et al. Kawasaki disease with dilatation of the common bile duct: A case report and review of literature[J]. Int J Rheum Dis, 2021, 24( 10): 1325- 1330. DOI: 10.1111/1756-185X.14208.
[33]	PRATAP K, GARDNER LS, GILLIS D, et al. Hepatic predominant presentation of Kawasaki disease in adolescence case report and review of literature[J]. BMC Gastroenterol, 2020, 20( 1): 352. DOI: 10.1186/s12876-020-01461-2.
[34]	UNAL F, CAKIR M, BARAN M, et al. Liver involvement in children with familial Mediterranean fever[J]. Dig Liver Dis, 2012, 44( 8): 689- 693. DOI: 10.1016/j.dld.2012.01.003.
[35]	BAYRAMOGLU Z, AKYOL SARI ZN, KOKER O, et al. Shear wave elastography evaluation of liver, pancreas, spleen and kidneys in patients with familial mediterranean fever and amyloidosis[J]. Br J Radiol, 2021, 94( 1128): 20210237. DOI: 10.1259/bjr.20210237.
[36]	FRAISSE T, SAVEY L, HENTGEN V, et al. Non-amyloid liver involvement in familial Mediterranean fever: A systematic literature review[J]. Liver Int, 2020, 40( 6): 1269- 1277. DOI: 10.1111/liv.14445.
[37]	AOKI M, IZAWA K, TANAKA T, et al. Case report: A pediatric case of familial Mediterranean fever concurrent with autoimmune hepatitis[J]. Front Immunol, 2022, 13: 917398. DOI: 10.3389/fimmu.2022.917398.
[38]	WANG W, WANG W, ZOU LP, et al. Clinical characteristics of 25 patients with type I interferonopathies[J]. Chin J Pediatr, 2021, 59( 12): 1043- 1047. DOI: 10.3760/cma.j.cn112140-20211004-00843. 王伟, 王薇, 邹丽萍, 等. Ⅰ型干扰素病25例临床特点分析[J]. 中华儿科杂志, 2021, 59( 12): 1043- 1047. DOI: 10.3760/cma.j.cn112140-20211004-00843.
[39]	GAVAZZI F, CROSS ZM, WOIDILL S, et al. Hepatic involvement in aicardi-goutières syndrome[J]. Neuropediatrics, 2021, 52( 6): 441- 447. DOI: 10.1055/s-0040-1722673.
[40]	ELHANI I, RILLER Q, BOURSIER G, et al. A20 haploinsufficiency: A systematic review of 177 cases[J]. J Investig Dermatol, 2024, 144( 6): 1282- 1294. DOI: 10.1016/j.jid.2023.12.007.
[41]	IWASA T, MIWA TK, UNOME S, et al. A case of A20 haploinsufficiency complicated by autoimmune hepatitis[J]. Hepatol Res, 2024, 54( 6): 606- 611. DOI: 10.1111/hepr.14003.
[42]	KIM HY, SONG JY, KIM WI, et al. The first case of an infant with familial A20 haploinsufficiency in Korea[J]. J Korean Med Sci, 2020, 35( 30): e252. DOI: 10.3346/jkms.2020.35.e252.
[43]	LI GM, LIU HM, GUAN WZ, et al. Expanding the spectrum of A20 haploinsufficiency in two Chinese families: Cases report[J]. BMC Med Genet, 2019, 20( 1): 124. DOI: 10.1186/s12881-019-0856-1.
[44]	DESHAYES S, BAZILLE C, KHOURI E EL, et al. Chronic hepatic involvement in the clinical spectrum of A20 haploinsufficiency[J]. Liver Int, 2021, 41( 8): 1894- 1900. DOI: 10.1111/liv.14935.
[45]	JINDAL AK, PILANIA RK, SURI D, et al. A young female with early onset arthritis, uveitis, hepatic, and renal granulomas: A clinical tryst with Blau syndrome over 20 years and case-based review[J]. Rheumatol Int, 2021, 41( 1): 173- 181. DOI: 10.1007/s00296-019-04316-6.
[46]	CROPLEY A, ASHRAFY AH, WELTMAN M. An original description of granulomatous liver cirrhosis in Blau syndrome[J]. Dig Dis Sci, 2019, 64( 11): 3346- 3349. DOI: 10.1007/s10620-019-05682-8.