MedStar Georgetown Transplant Institute, Pasquerilla Healthcare Center, Washington, DC, USA.
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Oncologist. 2020 Feb;25(2):105-111. doi: 10.1634/theoncologist.2018-0162. Epub 2019 Sep 9.
Immune checkpoint inhibitor treatment has been approved by the U.S. Food and Drug Administration for the treatment of a wide range of cancer types, including hepatocellular carcinoma. Workup and management of immune-mediated hepatitis, pancreatitis, or cholangitis that develops during immune checkpoint inhibitor treatment can be challenging. Immune-mediated hepatitis can be particularly challenging if patients have underlying viral hepatitis or autoimmune hepatitis. Patients with positive hepatitis B virus DNA should be referred to a hepatologist for antiviral therapy prior to immune checkpoint inhibitor treatment. With untreated hepatitis C virus (HCV) and elevated liver enzymes, a liver biopsy should be obtained to differentiate between HCV infection and immune-mediated hepatitis due to anti-programmed cell death protein 1 (PD-1) therapy. If autoimmune serologies are negative, then this supports a case of immune-mediated hepatitis secondary to anti-PD-1 therapy, rather than autoimmune hepatitis. In this case, an empiric steroid therapy is reasonable; however, if the patient does not respond to steroid therapy in 3-5 days, then liver biopsy should be pursued. The incidence of immune checkpoint-induced pancreatitis is low, but when it does occur, diagnosis is not straightforward. Although routine monitoring of pancreatic enzymes is not generally recommended, when pancreatitis is suspected, serum levels of amylase and lipase should be checked. Once confirmed, a steroid or other immunosuppressant (if steroids are contraindicated) should be administered along with close monitoring, and a slow tapering dosage once the pancreatitis is under control. Patients should then be monitored for recurrent pancreatitis. Finally, immune therapy-related cholangitis involves elevated bilirubin and alkaline phosphatase and, once diagnosed, is managed in the same way as immune-mediated hepatitis. KEY POINTS: Immune-mediated hepatitis, pancreatitis, and cholangitis are found in patients receiving or who have previously received immune checkpoint inhibitors. To work up immune-mediated hepatitis, viral, and autoimmune serologies, liver imaging will help to differentiate immune-mediated hepatitis from hepatitis of other etiology. Hepatology consult may be considered in patients with a history of chronic liver disease who developed hepatitis during immune checkpoint inhibitor treatment. Liver biopsy should be considered to clarify the diagnosis for case in which the hepatitis is refractory to steroid or immunosuppressant treatment. Immune-mediated pancreatitis is treated with steroid or other immunosuppressant with a slow tapering and should be monitored for recurrence.
免疫检查点抑制剂治疗已获美国食品和药物管理局批准，可用于治疗多种癌症类型，包括肝细胞癌。在接受免疫检查点抑制剂治疗期间，免疫介导性肝炎、胰腺炎或胆管炎的检查和管理可能具有挑战性。如果患者存在基础病毒性肝炎或自身免疫性肝炎，免疫介导性肝炎可能特别具有挑战性。对于乙型肝炎病毒 DNA 阳性的患者，应在接受免疫检查点抑制剂治疗之前转介给肝病专家进行抗病毒治疗。对于未经治疗的丙型肝炎病毒（HCV）和肝酶升高的患者，应进行肝活检以区分 HCV 感染和抗程序性细胞死亡蛋白 1（PD-1）治疗引起的免疫介导性肝炎。如果自身免疫血清学为阴性，则支持抗 PD-1 治疗继发的免疫介导性肝炎，而非自身免疫性肝炎。在这种情况下，经验性类固醇治疗是合理的；但是，如果患者在 3-5 天内对类固醇治疗无反应，则应进行肝活检。免疫检查点诱导性胰腺炎的发病率较低，但发生时诊断并不简单。虽然通常不建议常规监测胰腺酶，但怀疑胰腺炎时，应检查血清淀粉酶和脂肪酶水平。一旦确诊，应给予类固醇或其他免疫抑制剂（如果类固醇禁忌），同时密切监测，并在胰腺炎得到控制后逐渐减少剂量。然后应监测患者是否复发胰腺炎。最后，免疫治疗相关胆管炎伴有胆红素和碱性磷酸酶升高，一旦确诊，其治疗方法与免疫介导性肝炎相同。要点：接受或既往接受免疫检查点抑制剂治疗的患者可能出现免疫介导性肝炎、胰腺炎和胆管炎。为了检查免疫介导性肝炎，需要进行病毒和自身免疫血清学检查，肝脏影像学检查有助于将免疫介导性肝炎与其他病因引起的肝炎区分开来。对于在接受免疫检查点抑制剂治疗期间发生肝炎的慢性肝病患者，可考虑进行肝病专家会诊。对于类固醇或免疫抑制剂治疗无效的病例，应考虑肝活检以明确诊断。免疫介导性胰腺炎采用类固醇或其他免疫抑制剂治疗，逐渐减量，并应监测复发情况。
