当前或过去的乙型肝炎病毒感染患者免疫治疗期间的肝炎发

StephenW

Hepatitis Flare During Immunotherapy in Patients With Current or Past Hepatitis B Virus Infection
Grace Lai-Hung Wong  1 , Vincent Wai-Sun Wong, Vicki Wing-Ki Hui, Terry Cheuk-Fung Yip, Yee-Kit Tse, Lilian Yan Liang, Rashid Nok-Shun Lui, Tony Shu-Kam Mok, Henry Lik-Yuen Chan, Stephen Lam Chan
Affiliations
Affiliation

    1
    Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Translational Oncology, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China.

    PMID: 33560651 DOI: 10.14309/ajg.0000000000001142

Abstract

Introduction: Immunotherapy has dramatically improved the survival of patients with advanced or metastatic malignancies. Recent studies suggest that immunotherapy may increase the risk of hepatitis, whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy.

Methods: This was a territory-wide observational cohort study in Hong Kong. We identified patients through electronic medical records based on the prescriptions of immune checkpoint inhibitors from July 1, 2014, to December 31, 2019. Patients who were HBsAg positive or HBsAg negative with results for antibody to hepatitis B surface or core antigen (anti-HBs or anti-HBc) were included.

Results: A total of 990 patients (397 HBsAg-positive, 593 HBsAg-negative with 482 anti-HBc and/or anti-HBs positive, and 111 both anti-HBc and anti-HBs negative) were identified. All of HBsAg-positive and 15.9% HBsAg-negative patients were put on oral antiviral treatment. Hepatitis flare (alanine aminotransferase >2 times of the upper limit of normal) occurred in 39.3% HBsAg-positive and 30.4% HBsAg-negative patients. High baseline alanine aminotransferase and combination of immunotherapy increased the risk of hepatitis. HBV reactivation (≥2 log increase in HBV DNA from baseline) occurred in 2 HBsAg-positive patients; HBsAg seroclearance and seroreversion was observed in 1 HBsAg-positive and 1 HBsAg-negative patient, respectively (<1%).

Discussion: Hepatitis flare occurs in approximately 40% of HBsAg-positive patients and 30% of HBsAg-negative patients during immunotherapy. HBV reactivation, HBsAg seroclearance, and HBsAg seroreversion are rare. Current or past HBV infection has no impact on the emergence of hepatic flare associated with immunotherapy.

Copyright © The American College of Gastroenterology 2021. All Rights Reserved.

StephenW

当前或过去的乙型肝炎病毒感染患者免疫治疗期间的肝炎发作
黄丽红1，黄文顺，许永基，叶德凤，叶洁洁，颜莉莲，吕德顺，莫树锦，莫文蔚陈林霖
隶属关系
联系

    1个
    中国香港特别行政区香港中文大学医学数据分析中心；香港中文大学，香港特别行政区医学与治疗学系；香港中文大学消化病研究所，香港特别行政区；香港中文大学，香港特别行政区临床肿瘤学系，转化肿瘤学国家重点实验室。

    PMID：33560651 DOI：10.14309 / ajg.0000000000001142

抽象的

简介：免疫疗法极大地改善了晚期或转移性恶性肿瘤患者的生存率。最近的研究表明，免疫疗法可能会增加患肝炎的风险，同时也可能诱导慢性乙型肝炎病毒（HBV）感染的功能治愈。我们评估了接受免疫治疗的当前或过去HBV感染患者的肝炎发作，HBV活化，乙肝表面抗原（HBsAg）血清清除或血清逆转的发生率。

方法：这是一项在香港范围内的观察性队列研究。我们根据2014年7月1日至2019年12月31日免疫检查点抑制剂的处方，通过电子病历对患者进行了鉴定。HBsAg阳性或HBsAg阴性的患者的乙肝表面或核心抗原抗体（抗HBs）或抗HBc）。

结果：共鉴定了990例患者（397 HBsAg阳性，593 HBsAg阴性，482例抗-HBc和/或抗-HBs阳性，111例抗-HBc和抗-HBs阴性）。所有的HBsAg阳性患者和15.9％HBsAg阴性患者均接受口服抗病毒治疗。 39.3％HBsAg阳性和30.4％HBsAg阴性的患者发生肝炎发作（丙氨酸氨基转移酶>正常上限的2倍）。高基线丙氨酸转氨酶和免疫治疗相结合会增加患肝炎的风险。 2例HBsAg阳性患者发生HBV再激活（HBV DNA较基线增加≥2log）。分别在1例HBsAg阳性和1例HBsAg阴性的患者中观察到HBsAg血清清除和血清逆转（<1％）。

讨论：在免疫治疗期间，约40％的HBsAg阳性患者和30％的HBsAg阴性患者发生肝炎发作。很少发生HBV激活，HBsAg血清清除和HBsAg逆转。当前或过去的HBV感染对与免疫疗法相关的肝耀斑的出现没有影响。

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