Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System, Ann Arbor, Michigan.
Pharmacotherapy. 2017 Dec;37(12):1578-1585. doi: 10.1002/phar.2036. Epub 2017 Nov 21.
Primary sclerosing cholangitis (PSC) frequently progresses to end-stage liver disease and cirrhosis, requiring liver transplantation. Approximately 70% of patients with PSC have concomitant inflammatory bowel disease (IBD) during their clinical course. After liver transplantation for PSC, corticosteroids and other high-intensity immunosuppressants are initiated to keep IBD in remission. Patients with IBD that is refractory to these agents may need to be managed with biologic therapies. Biologic agents, however, may further increase the risks for malignancy and infection due to their immunosuppressive effects. Thus, to gain a better understanding of the risks and benefits of these agents in this high-risk patient population, we performed a literature search of the PubMed database (2002-2017) to identify studies assessing the efficacy and safety of various biologic agents for the management of IBD in liver transplant recipients. No randomized controlled studies or retrospective comparative studies were identified; however, 15 case reports and case series were identified that met our inclusion criteria. From these case reports, we identified 67 patients who developed de novo or recurrent IBD after liver transplantation and received anti-tumor necrosis factor-α or anti-integrin therapy. Of the 13 published cases reporting clinical response or remission of IBD activity in liver transplant recipients (59 patients), clinical response or remission of IBD was reported in 38 (64.4%) of those patients. Adverse complications reported included cholangitis, oral candidiasis, Clostridium difficile colitis, bacterial pneumonia, cryptosporidiosis, Epstein-Barr virus-positive posttransplantation lymphoproliferative disease, and hepatotoxicity. Given the limited literature (case reports and case series) highlighted in this review, biologic agents such as tumor necrosis factor-α inhibitors and integrin inhibitors commonly used for moderate to severe IBD may be appropriate after liver transplantation; however, consideration of risk versus benefit should always occur in a patient-specific manner.
原发性硬化性胆管炎（PSC）常进展为终末期肝病和肝硬化，需要进行肝移植。大约 70%的 PSC 患者在其临床病程中同时患有炎症性肠病（IBD）。在 PSC 患者进行肝移植后，会使用皮质类固醇和其他高强度免疫抑制剂来使 IBD 缓解。对于这些药物无效的 IBD 患者，可能需要使用生物疗法进行治疗。然而，由于生物制剂的免疫抑制作用，可能会进一步增加恶性肿瘤和感染的风险。因此，为了更好地了解这些药物在高危患者人群中的风险和益处，我们对 PubMed 数据库（2002-2017 年）进行了文献检索，以确定评估各种生物制剂治疗肝移植受者 IBD 的疗效和安全性的研究。未发现随机对照研究或回顾性比较研究，但确定了符合纳入标准的 15 例病例报告和病例系列。从这些病例报告中，我们确定了 67 例在肝移植后发生新的或复发性 IBD 并接受抗肿瘤坏死因子-α或抗整合素治疗的患者。在报告肝移植受者 IBD 活动临床缓解或缓解的 13 个已发表病例（59 例）中，有 38 例（64.4%）患者报告了 IBD 的临床缓解或缓解。报告的不良并发症包括胆管炎、口腔念珠菌病、艰难梭菌结肠炎、细菌性肺炎、隐孢子虫病、EB 病毒阳性移植后淋巴组织增生性疾病和肝毒性。鉴于本综述中强调的有限文献（病例报告和病例系列），肿瘤坏死因子-α抑制剂和整合素抑制剂等生物制剂可能适合在肝移植后使用，用于治疗中重度 IBD；然而，应始终根据患者的具体情况权衡风险与获益。
