非酒精性脂肪性肝病及原发性肝细胞癌患者接种新型冠状病毒灭活疫苗的安全性及免疫原性

doi:10.19871/j.cnki.xfcrbzz.2022.03.011

新发传染病电子杂志 ›› 2022, Vol. 7 ›› Issue (3): 50-54.doi: 10.19871/j.cnki.xfcrbzz.2022.03.011

非酒精性脂肪性肝病及原发性肝细胞癌患者接种新型冠状病毒灭活疫苗的安全性及免疫原性

刘星¹, 吴威², 张晓明³, 李强³, 权冬梅², 张朕¹, 戴越³, 张麟格¹, 宋冠男², 李欣悦¹, 朱一丹⁴, 王岩¹

1. 沈阳市第六人民医院科教科,沈阳 110006;沈阳市第六人民医院肝癌诊治中心,沈阳 110006;
3. 沈阳市第六人民医院检验科,沈阳 110006;
4. 日本冈山大学医齿药学综合研究所呼吸器乳腺内分泌外科,冈山 700-8530

收稿日期:2022-01-11 出版日期:2022-07-31 发布日期:2022-09-08
通讯作者: 王岩,Email：Professor_wangyan@163.com
基金资助:
沈阳市新发突发传染病诊断及治疗医学研究中心项目

Safety and immunogenicity of SARS-CoV-2 inactivated vaccination in patients with NAFLD and liver cancer

Liu Xing¹, Wu Wei², Zhang Xiaoming³, Li Qiang³, Quan Dongmei², Zhang Zhen¹, Dai Yue³, Zhang Linge¹, Song Guannan², Li Xinyue¹, Zhu Yidan⁴, Wang Yan¹

1. Science and Education Department, The Sixth People's Hospital of Shenyang, Shenyang, 110006, China;
2. Diagnosis and Treatment Center of Hepatocellular Carcinoma, The Sixth People's HosPital of Shenyang, Shenyang 110006, China;
3. Clinical Laboratory, The Sixth People's HosPital of Shenyang, Shenyang 110006, China;
4. Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan

Received:2022-01-11 Online:2022-07-31 Published:2022-09-08

摘要/Abstract

摘要： 目的探讨新型冠状病毒疫苗在非酒精性脂肪性肝病（NAFLD）患者以及原发性肝细胞癌患者中的安全性及免疫原性。方法纳入2020年12月至2021年10月到沈阳市第六人民医院就诊自愿接种新型冠状病毒灭活疫苗的健康人群30例（健康组）、NAFLD患者30例（NAFLD组）、原发性肝细胞癌患者10例（肝癌组）以及新型冠状病毒肺炎（COVID-19）患者10例（COVID-19组）。健康组、NAFLD组接种3剂灭活疫苗;肝癌组接种2剂灭活疫苗,检测每剂疫苗接种后中和抗体及肝功能水平,在前2剂疫苗每次接种后对健康组和肝癌组进行T淋巴细胞亚群计数,同时记录各组人群疫苗接种后不良反应发生状况。并检测COVID-19患者治愈后半年的中和抗体水平。结果健康组、NAFLD组和肝癌组三组人群随着疫苗接种剂次增加,中和抗体水平呈现逐渐上升的趋势,健康组和NAFLD组接种第3剂疫苗后中和抗体水平均高于COVID-19患者临床治愈后半年的水平。健康人群和肝癌患者接种疫苗后均表现出CD4+T淋巴细胞和CD4+T淋巴细胞百分比升高,同时伴有CD8+T淋巴细胞的增加。注射部位疼痛是最常见的不良反应。结论新型冠状病毒灭活疫苗对肝病患者具有较好的安全性和免疫原性。第3剂疫苗加强接种尤其适用于少数需要加大疫苗剂量以获得更好反应的肝病患者以及接种常规2剂疫苗无法产生免疫应答的特定人群。

关键词: 新型冠状病毒, 新型冠状病毒肺炎, 疫苗, 非酒精性脂肪性肝病, 肝癌

Abstract: Objective To investigate the safety and immunogenicity of COVID-19 vaccination in patients with nonalcoholic fatty liver disease (NAFLD) and patients with primary hepatocellular carcinoma (HCC). Method Ten COVID-19 patients who had been infected with SARS-CoV-2 and people who voluntarily vaccinated with COVID-19 inactivated vaccine (including 30 Healthy people, 30 NAFLD patients and 10 HCC patients) between December 2020 and October 2021 in the Sixth People's Hospital of Shenyang were enrolled in the study. The healthy group and NAFLD group were vaccinated with 3 doses and the HCC group was vaccinated with 2 doses. The neutralizing antibody (nAb) and liver function after each dose were detected, and the T lymphocyte subsets of the healthy group and the HCC group were tested after the first two doses. The occurrence of adverse reactions after vaccination in each group was recorded. The nAb of COVID-19 patients after 6 months' treatment was also detected. Result The nAb level in healthy group, NAFLD group and HCC group increased gradually with the increase of vaccine doses. The nAb level in healthy group and NAFLD group after the third dose of vaccine were higher than those in COVID-19 patients after 6 months' treatment. CD4+T and CD4+T% were increased in both healthy group and HCC group after vaccination, accompanied by an increase of CD8+T. Injection site pain was the most common adverse reaction. Conclusion COVID-19 inactivated vaccination was safety and has good immunogenicity in patients with liver disease. The third dose is especially suitable for a small number of patients with liver diseases who need to increase the vaccine dose to obtain a better response, and specific people who cannot produce immune response by conventional two doses.

Key words: Severe acute respiratory syndrome coronavirus 2, Coronavirus disease 2019, Vaccine, Nonalcoholic fatty liver disease, Liver cancer

刘星, 吴威, 张晓明, 李强, 权冬梅, 张朕, 戴越, 张麟格, 宋冠男, 李欣悦, 朱一丹, 王岩. 非酒精性脂肪性肝病及原发性肝细胞癌患者接种新型冠状病毒灭活疫苗的安全性及免疫原性[J]. 新发传染病电子杂志, 2022, 7(3): 50-54.

Liu Xing, Wu Wei, Zhang Xiaoming, Li Qiang, Quan Dongmei, Zhang Zhen, Dai Yue, Zhang Linge, Song Guannan, Li Xinyue, Zhu Yidan, Wang Yan. Safety and immunogenicity of SARS-CoV-2 inactivated vaccination in patients with NAFLD and liver cancer[J]. Electronic Journal of Emerging Infectious Diseases, 2022, 7(3): 50-54.

参考文献

[1] WANG J, HOU Z, LIU J, et al.Safety and immunogenicity of COVID-19 vaccination in Patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study[J]. J HePatol, 2021, 75(2):439-441.
[2] 郝鹏飞,许汪,杜寿文,等.冠状病毒起源、受体及新型冠状病毒检测与疫苗最新研究进展[J/CD].新发传染病电子杂志, 2020, 5(2): 74-78,60.
[3] PORTINCASA P, KRAWCZYK M, SMYK W, et al.COVID-19 and non-alcoholic fatty liver disease: Two intersecting Pandemics[J]. Eur J Clin Invest, 2020, 50(10):e13338.
[4] QI X, LIU Y, WANG J, et al.Clinical course and risk factors for mortality of COVID-19 Patients with Pre-existing cirrhosis: a multicentre cohort study[J]. Gut, 2021, 70(2):433-436.
[5] ALQAHTANI SA, SCHATTENBERG JM.NAFLD in the Elderly[J]. Clin Interv Aging, 2021, 16:1633-1649.
[6] ALBERTI KG, ECKEL RH, GRUNDY SM, et al.Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity[J]. Circulation, 2009, 120(16):1640-1645.
[7] ZHANG Y, ZENG G, PAN H, et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, Placebo-controlled, Phase 1/2 clinical trial[J]. Lancet Infect Dis, 2021, 21(2):181-192.
[8] XIA S, ZHANG Y, WANG Y, et al.Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, Placebo-controlled, Phase 1/2 trial[J]. Lancet Infect Dis, 2021, 21(1):39-51.
[9] AMJAD W, ALUKAL J, ZHANG T, et al.Two-Dose HePatitis B Vaccine (HePlisav-B) Results in Better Seroconversion Than Three-Dose Vaccine (Engerix-B) in Chronic Liver Disease[J]. Dig Dis Sci, 2021, 66(6):2101-2106.
[10] LIU J, WU H, CHEN H.Immune response to hepatitis B vaccine in Patients with chronic hepatitis C infection: A systematic review and meta-analysis[J]. Hepatol Res, 2018, 48(2): 119-126.
[11] CORNBERG M, BUTI M, EBERHARDT CS, et al.EASL Position Paper on the use of COVID-19 vaccines in Patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients[J]. J HePatol, 2021, 74(4):944-951.
[12] ASLAM S, GOLDSTEIN DR, VOS R, et al.COVID-19 vaccination in our transplant recipients: The time is now[J]. J Heart Lung Transplant, 2021, 40(3):169-171.
[13] ZIMMERMANN P, CURTIS N.Factors That Influence the Immune Response to Vaccination[J]. Clin Microbiol Rev, 2019, 32(2):e00084-18.
[14] ALBILLOS A, LARIO M, ÁLVAREZ-MON M.Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance[J]. J HePatol, 2014, 61(6):1385-1396.
[15] 吴荷宁, 彭民. CD4+T、CD8+T淋巴细胞在新型冠状病毒肺炎中的研究进展[J]. 天津医科大学学报, 2021, 27(6):658-660,664.
[16] 谢水林, 顾为望, 陆家海, 等. SARS灭活疫苗的实验免疫初步研究[J]. 动物医学进展, 2004,(4):88-90.
[17] GANJI A, FARAHANI I, KHANSARINEJAD B, et al.Increased expression of CD8 marker on T-cells in COVID-19 Patients[J]. Blood Cells Mol Dis, 2020, 83:102437.
[18] 李倩,卢洪洲.新型冠状病毒疫苗研究最新进展[J/CD].新发传染病电子杂志, 2020, 5(4): 268-273.
[19] 袁静,谭晓华,王福祥,等.恶性肿瘤患者SARS-CoV-2疫苗接种的专家意见[J/CD].新发传染病电子杂志,2022,7(2):1-5.
[20] FU J, ZHANG Z, ZHOU L, et al.Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma[J]. Hepatology, 2013, 58(1): 139-149.
[21] ZHENG X, JIN W, WANG S, et al.Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma[J]. Front Immunol, 2021, 12:729705.
[22] 孟彤彤, 孔庆福, 王富珍, 等. 新型冠状病毒灭活疫苗研究进展[J].中国疫苗和免疫, 2020, 26(5):590-596.
[23] NGUYEN THO, ROWNTREE LC, PETERSEN J, et al. CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity[J]. Immunity,2021, 54(5): 1066 -1082. e5.
[24] MARTINA E. MCMENAMIN, JOSHUA NEALON, YUN LIN, et al. Vaccine effectiveness of two and three doses of BNT162b2 1 and CoronaVac against COVID-19 in Hong Kong[DB/OL].[2022-07-11]. https://www.medrxiv.org/content/10.1101/2022.03.22.22272769v1.
[25] MOK CKP, COHEN CA, CHENG SMS, et al.Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong[J]. Respirology, 2022, 27(4): 301-310.
[26] 廖晓艳,高丰光.树突状细胞交叉提呈的研究进展[J].中国免疫学杂志, 2021, 37(22):2699-2703.

非酒精性脂肪性肝病及原发性肝细胞癌患者接种新型冠状病毒灭活疫苗的安全性及免疫原性

Safety and immunogenicity of SARS-CoV-2 inactivated vaccination in patients with NAFLD and liver cancer

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