肝胆癌患者接种严重急性呼吸系统综合征冠状病毒2型疫苗后免疫反应不足:被遗忘的弱势患者群体。

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-05-10 eCollection Date: 2023-09-01 DOI:10.1159/000529608
Malte B Monin, Leona I Baier, Jens G Gorny, Moritz Berger, Taotao Zhou, Robert Mahn, Farsaneh Sadeghlar, Christian Möhring, Christoph Boesecke, Kathrin van Bremen, Jürgen K Rockstroh, Christian P Strassburg, Anna-Maria Eis-Hübinger, Matthias Schmid, Maria A Gonzalez-Carmona
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引用次数: 1

摘要

引言:肝胆癌(HBC)患者接种严重急性呼吸系统综合征冠状病毒2型疫苗后的免疫应答率数据很少。然而,由于慢性肝病(CLD)与恶性肿瘤和抗癌治疗的结合,免疫原性必须受损。方法:在这项前瞻性纵向研究中,纳入了101名患者,其中59名是正在接受抗癌治疗的HBC患者。一组既往有胃肠道癌症病史的患者作为对照,其中28.6%的患者患有HBC,但未检测到活动性肿瘤疾病,已停止治疗至少12个月。比较了严重急性呼吸系统综合征冠状病毒2型抗刺突IgG、替代中和抗体(sNABs)和细胞免疫反应的水平。在单因素和多因素亚组分析中,考虑了免疫原性受损的危险因素。记录了严重急性呼吸系统综合征冠状病毒2型感染率和临床病程的数据。结果:在接受积极治疗的HBC患者中,两次接种疫苗4周后,严重急性呼吸系统综合征冠状病毒2型抗刺突IgG水平(2.55 log10 BAU/mL;95%可信区间:2.33-2.76;p<0.01)显著低于接受随访的患者(3.02 log10 BAU/mL;95%置信区间:2.80-3.25)。抗体水平随着时间的推移而下降,两组之间的差异也减少了。然而,在更长的时间内,接受治疗的HBC患者的严重急性呼吸系统综合征冠状病毒2型sNAB滴度(64.19%;95%可信区间:55.90-72.48;p<0.01)显著低于接受后续护理的患者(84.13%;95%置信区间:76.95-91.31)。潜在的CLD和/或肝硬化Child-Pugh a或B(低于8分)似乎没有进一步损害免疫原性。相反,化疗和额外的免疫抑制被发现可以显著降低抗体水平。在第三次接种严重急性呼吸系统综合征冠状病毒2型加强针后,两组之间的总抗体和中和抗体水平持平。此外,细胞反应率是平衡的。临床上,严重急性呼吸系统综合征冠状病毒2型的感染率较低,没有观察到严重的病程。结论:活动性HBC患者对严重急性呼吸系统综合征冠状病毒2型基础疫苗的免疫应答率显著受损,尤其是在化疗期间,与潜在的肝硬化或非肝硬化CLD无关。尽管加强疫苗接种平衡了差异,但随着时间的推移,免疫力下降,应进行监测,以获得进一步的建议。我们的数据有助于临床医生决定对感染严重急性呼吸系统综合征冠状病毒2型的HBC患者进行个人额外的加强针接种和/或被动免疫或抗病毒治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients.

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment.

Methods: In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented.

Results: In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log10 BAU/mL; 95% CI: 2.33-2.76; p < 0.01) than in patients in follow-up care (3.02 log10 BAU/mL; 95% CI: 2.80-3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90-72.48; p < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95-91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed.

Conclusion: Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.

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来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
期刊最新文献
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