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.
Am J Gastroenterol. 2021 Jun 1;116(6):1274-1283. doi: 10.14309/ajg.0000000000001142.
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.
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.
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%).
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.
免疫疗法显著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）感染的功能性治愈。我们评估了目前或既往 HBV 感染者接受免疫治疗后肝炎发作、HBV 再激活、乙肝表面抗原（HBsAg）血清清除或血清转换的发生率。
这是一项在香港进行的全港范围观察性队列研究。我们通过电子病历根据 2014 年 7 月 1 日至 2019 年 12 月 31 日免疫检查点抑制剂的处方确定患者。包括 HBsAg 阳性或 HBsAg 阴性但 HBV 表面或核心抗原抗体（抗-HBs 或抗-HBc）阳性的患者。
共纳入 990 例患者（397 例 HBsAg 阳性，593 例 HBsAg 阴性，其中 482 例抗-HBc 和/或抗-HBs 阳性，111 例抗-HBc 和抗-HBs 均阴性）。所有 HBsAg 阳性患者和 15.9% HBsAg 阴性患者均接受口服抗病毒治疗。HBsAg 阳性患者中 39.3%和 HBsAg 阴性患者中 30.4%发生肝炎发作（丙氨酸氨基转移酶>正常上限的 2 倍）。高基线丙氨酸氨基转移酶和免疫治疗联合增加了肝炎的风险。2 例 HBsAg 阳性患者发生 HBV 再激活（HBV DNA 较基线升高≥2 对数）；1 例 HBsAg 阳性患者和 1 例 HBsAg 阴性患者发生 HBsAg 血清清除和血清转换（分别为<1%）。
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。HBV 再激活、HBsAg 血清清除和 HBsAg 血清转换较为罕见。目前或既往 HBV 感染对免疫治疗相关肝性发作的发生无影响。
