难治性难治性自身免疫性肝炎:药物治疗的最新进展。

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY
Sayan Malakar, Umair Shamsul Hoda, Suprabhat Giri, Arghya Samanta, Akash Roy, Rajat Gupta, S Rakesh Kumar, Mayank Agarwal, Anubhav Pawar, Sumit Rungta, Uday C Ghoshal
{"title":"难治性难治性自身免疫性肝炎:药物治疗的最新进展。","authors":"Sayan Malakar, Umair Shamsul Hoda, Suprabhat Giri, Arghya Samanta, Akash Roy, Rajat Gupta, S Rakesh Kumar, Mayank Agarwal, Anubhav Pawar, Sumit Rungta, Uday C Ghoshal","doi":"10.4254/wjh.v17.i9.110264","DOIUrl":null,"url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The exact pathophysiology of AIH is unknown. Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH. Immunosuppressive therapy is the mainstay of treatment; however, 10%-25% of patients with AIH may not respond to primary therapy. Those patients are often salvaged with second- and third-line immunosuppressive therapy. Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy. Concurrent metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, overlap syndrome (AIH with primary biliary cholangitis or sclerosing cholangitis), chronic hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection should be ruled out in such cases. Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission. Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids, azathioprine, or other immunosuppressive agents. Second- and third-line immunosuppressive agents include mycophenolate mofetil, cyclosporine, tacrolimus, infliximab, and rituximab. Patients with AIH may present with acute severe AIH (AS-AIH) and AIH-related acute on chronic liver failure, and they often require liver transplantation. The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition. Difficult-to-treat AIH includes patients with intolerable side effects, fulminant disease (AIH with acute on chronic liver failure and AS-AIH), AIH in pregnancy, and HIV infection. Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH. This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 9","pages":"110264"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476786/pdf/","citationCount":"0","resultStr":"{\"title\":\"Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management.\",\"authors\":\"Sayan Malakar, Umair Shamsul Hoda, Suprabhat Giri, Arghya Samanta, Akash Roy, Rajat Gupta, S Rakesh Kumar, Mayank Agarwal, Anubhav Pawar, Sumit Rungta, Uday C Ghoshal\",\"doi\":\"10.4254/wjh.v17.i9.110264\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The exact pathophysiology of AIH is unknown. Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH. Immunosuppressive therapy is the mainstay of treatment; however, 10%-25% of patients with AIH may not respond to primary therapy. Those patients are often salvaged with second- and third-line immunosuppressive therapy. Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy. Concurrent metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, overlap syndrome (AIH with primary biliary cholangitis or sclerosing cholangitis), chronic hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection should be ruled out in such cases. Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission. Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids, azathioprine, or other immunosuppressive agents. Second- and third-line immunosuppressive agents include mycophenolate mofetil, cyclosporine, tacrolimus, infliximab, and rituximab. Patients with AIH may present with acute severe AIH (AS-AIH) and AIH-related acute on chronic liver failure, and they often require liver transplantation. The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition. Difficult-to-treat AIH includes patients with intolerable side effects, fulminant disease (AIH with acute on chronic liver failure and AS-AIH), AIH in pregnancy, and HIV infection. Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH. This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.</p>\",\"PeriodicalId\":23687,\"journal\":{\"name\":\"World Journal of Hepatology\",\"volume\":\"17 9\",\"pages\":\"110264\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476786/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Hepatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4254/wjh.v17.i9.110264\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Hepatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4254/wjh.v17.i9.110264","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

自身免疫性肝炎(AIH)是一种罕见的慢性肝脏疾病。AIH的确切病理生理机制尚不清楚。对肝脏抗原的自我耐受性的破坏和分子模仿通常与AIH的发病机制有关。免疫抑制疗法是主要的治疗方法;然而,10%-25%的AIH患者可能对初始治疗无反应。这些患者通常通过二线和三线免疫抑制治疗来挽救。对原发性免疫抑制治疗无效的患者应检查其他伴发疾病。同时伴有代谢功能障碍相关的脂肪变性肝病、酒精相关肝病、重叠综合征(AIH合并原发性胆道胆管炎或硬化性胆管炎)、慢性乙型肝炎病毒、丙型肝炎病毒和人类免疫缺陷病毒感染应被排除。针对伴随的病因可能导致临床症状的解决,并诱导生化和组织学的缓解。没有其他病因导致肝损伤的孤立性AIH应使用更高剂量的类固醇、硫唑嘌呤或其他免疫抑制剂进行治疗。二线和三线免疫抑制剂包括霉酚酸酯、环孢素、他克莫司、英夫利昔单抗和利妥昔单抗。AIH患者可能出现急性严重AIH (AS-AIH)和AIH相关急性慢性肝衰竭,通常需要肝移植。难治性AIH和难治性AIH这两个术语可以互换使用,没有明确的定义。难以治疗的AIH包括难以忍受的副作用、暴发性疾病(AIH伴有急性或慢性肝功能衰竭和AS-AIH)、妊娠期AIH和HIV感染。对标准的一线免疫抑制治疗无效的患者应归类为难治性AIH。本文综述了在治疗难治性AIH方面的问题,以及最近在药物管理方面的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management.

Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The exact pathophysiology of AIH is unknown. Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH. Immunosuppressive therapy is the mainstay of treatment; however, 10%-25% of patients with AIH may not respond to primary therapy. Those patients are often salvaged with second- and third-line immunosuppressive therapy. Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy. Concurrent metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, overlap syndrome (AIH with primary biliary cholangitis or sclerosing cholangitis), chronic hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection should be ruled out in such cases. Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission. Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids, azathioprine, or other immunosuppressive agents. Second- and third-line immunosuppressive agents include mycophenolate mofetil, cyclosporine, tacrolimus, infliximab, and rituximab. Patients with AIH may present with acute severe AIH (AS-AIH) and AIH-related acute on chronic liver failure, and they often require liver transplantation. The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition. Difficult-to-treat AIH includes patients with intolerable side effects, fulminant disease (AIH with acute on chronic liver failure and AS-AIH), AIH in pregnancy, and HIV infection. Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH. This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
World Journal of Hepatology
World Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
4.10
自引率
4.20%
发文量
172
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信