María Rojas-Feria, Manuel Castro, Emilio Suárez, Javier Ampuero, Manuel Romero-Gómez, Unit for Medical and Surgical Management of Digestive Diseases and CIBERehd, Valme University Hospital, University of Seville, E-41014 Sevilla, Spain.
World J Gastroenterol. 2013 Nov 14;19(42):7327-40. doi: 10.3748/wjg.v19.i42.7327.
Abnormal liver biochemical tests are present in up to 30% of patients with inflammatory bowel disease (IBD), and therefore become a diagnostic challenge. Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn's disease and ulcerative colitis (UC), and typically do not correlate with intestinal activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation of IBD, and is more prevalent in UC. Approximately 5% of patients with UC develop PSC, with the prevalence reaching up to 90%. Cholangiocarcinoma and colon cancer risks are increased in these patients. Less common disorders include autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cirrhosis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, liver abscess, and non-alcoholic fatty liver disease. Hepatitis B reactivation during immunosuppressive therapy is a major concern, with screening and vaccination being recommended in serologically negative cases for patients with IBD. Reactivation prophylaxis with entecavir or tenofovir for 6 to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen (HBsAg) positive, independently from viral load. HBsAg negative and anti-HBc positive patients, with or without anti-HBs, should be closely monitored, measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy, and should be treated if the viral load increases. On the other hand, immunosuppressive therapy does not seem to promote reactivation of hepatitis C, and hepatitis C antiviral treatment does not influence IBD natural history either. Most of the drugs used for IBD treatment may induce hepatotoxicity, although the incidence of serious adverse events is low. Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant. Methotrexate-related hepatotoxicity has been described in 14% of patients with IBD, in a dose-dependent manner. Liver biopsy is not routinely recommended. Biologics-related hepatotoxicity is rare, but has been shown most frequently in patients treated with infliximab. Thiopurines have been associated with veno-occlusive disease, regenerative nodular hyperplasia, and liver peliosis. Routine liver biochemical tests are recommended, especially during the first month of treatment. All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement. Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.
异常的肝功能生化检查在高达 30%的炎症性肠病 (IBD) 患者中存在，因此成为诊断难题。肝脏和胆道疾病是克罗恩病和溃疡性结肠炎 (UC) 的常见肠外表现，通常与肠道活动无关。原发性硬化性胆管炎 (PSC) 是 IBD 最常见的肝胆表现，在 UC 中更为常见。大约 5%的 UC 患者会发展为 PSC，患病率高达 90%。这些患者的胆管癌和结肠癌风险增加。较少见的疾病包括自身免疫性肝炎/PSC 重叠综合征、IgG4 相关胆管病、原发性胆汁性肝硬化、肝淀粉样变性、肉芽肿性肝炎、胆石症、门静脉血栓形成、肝脓肿和非酒精性脂肪性肝病。免疫抑制治疗期间乙型肝炎病毒再激活是一个主要问题，建议对 IBD 患者进行血清学阴性病例的筛查和疫苗接种。对于乙型肝炎表面抗原 (HBsAg) 阳性的患者，在免疫抑制治疗结束后 6 至 12 个月内必须使用恩替卡韦或替诺福韦进行再激活预防，而与病毒载量无关。HBsAg 阴性和抗-HBc 阳性的患者，无论是否有抗-HBs，都应密切监测，在治疗结束后 12 个月内测量丙氨酸氨基转移酶和乙型肝炎病毒 DNA，如果病毒载量增加则进行治疗。另一方面，免疫抑制治疗似乎不会促进丙型肝炎病毒的再激活，丙型肝炎病毒抗病毒治疗也不会影响 IBD 的自然病程。大多数用于治疗 IBD 的药物可能会引起肝毒性，尽管严重不良事件的发生率较低。与氨基水杨酸盐相关的肝功能生化检查异常并不常见，通常无临床意义。在 IBD 患者中，有 14%的患者出现了甲氨蝶呤相关的肝毒性，且呈剂量依赖性。通常不建议进行肝活检。生物制剂相关的肝毒性很少见，但在接受英夫利昔单抗治疗的患者中最常见。硫唑嘌呤与静脉阻塞性疾病、再生性结节性增生和肝血窦扩张有关。建议进行常规的肝功能生化检查，特别是在治疗的第一个月。对于有临床或生化特征提示肝胆受累的 IBD 患者，应考虑到所有这些情况。这些疾病的诊断和治疗通常涉及到肝病专家和胃肠病专家，因为其复杂性。
