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.

中文翻译：

---

肝胆癌患者接种 SARS-CoV-2 疫苗后免疫反应不足：一群被遗忘的弱势患者。

简介 肝胆癌 (HBC) 患者接种严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 疫苗后的免疫反应率数据很少。然而，由于慢性肝病（CLD）与恶性肿瘤和抗癌治疗相结合，免疫原性可能会受损。方法 在这项前瞻性纵向研究中，纳入了 101 名患者，其中 59 名是接受抗癌治疗的 HBC 患者。一组既往有胃肠癌病史的患者作为对照，其中 28.6% 患有 HBC，但未检测到活动性肿瘤疾病，并且已停止治疗至少 12 个月。比较了 SARS-CoV-2 抗刺突 IgG、替代中和抗体 (sNAB) 和细胞免疫反应的水平。在单变量和多变量亚组分析中，考虑了免疫原性受损的危险因素。记录了 SARS-CoV-2 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，SARS-CoV-2 抗尖峰 IgG 水平显着低于接受后续护理的患者（2.55 log10 BAU/mL；95% CI：2.33-2.76；p < 0.01） （3.02 log10 BAU/mL；95% CI：2.80-3.25）两次疫苗接种后 4 周。抗体水平随着时间的推移而下降，各组之间的差异也逐渐缩小。然而，接受治疗的 HBC 患者的 SARS-CoV-2 sNAB 滴度在较长时间内显着低于随访治疗患者 (84.13%；95% CI：55.90-72.48；p < 0.01)。 ；95% CI：76.95-91.31）。潜在的 CLD 和/或肝硬化 Child-Pugh A 或 B（低于 8 分）似乎不会进一步损害免疫原性。相反，化疗和额外的免疫抑制可显着降低抗体水平。在第三次 SARS-CoV-2 加强疫苗接种后，各组之间的总抗体和中和抗体水平相等。此外，细胞反应率是平衡的。临床上，SARS-CoV-2 感染率较低，且未观察到严重病程。结论 活动性 HBC 患者对 SARS-CoV-2 基本疫苗接种的免疫反应率显着受损，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，但随着时间的推移观察到免疫力逐渐减弱，应进行监测以获得进一步的建议。我们的数据帮助临床医生决定对感染 SARS-CoV-2 的 HBC 患者进行单独的额外加强疫苗接种和/或被动免疫或抗病毒治疗。