SARS-CoV-2 vaccination in patients with liver disease: responding to the next big question.
SARS-CoV-2 vaccination in patients with liver disease: responding to the next big question.
复制标题
DOI：
10.1016/s2468-1253(21)00008-x
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Barnes E
中科院分区：
文献类型：
--
作者：
Marjot T;Webb GJ;Barritt AS;Ginès P;Lohse AW;Moon AM;Pose E;Trivedi P;Barnes E
自 COVID-19 大流行爆发以来，SARS-CoV-2 疫苗的开发以前所未有的速度取得进展，最近的 3 期试验数据提供了实现群体免疫的诱人前景。 1-3 到目前为止，研究人员一直关注特定肝病表型（包括移植和免疫抑制）对 COVID-19 易感性和结果的影响。然而，肝病学界现在必须紧急将注意力转向描述这些弱势患者群体对 SARS-CoV-2 疫苗反应的特征。辉瑞/BioNTech BNT162b2 mRNA、Moderna mRNA-1273 和阿斯利康/牛津大学 ChAdOx1-nCoV-19 黑猩猩腺病毒 (ChAd) 载体疫苗均报告了出色的安全性，在预防症状性 COVID-19 方面具有显着功效 (62-95%)，并且均已获得快速监管批准。 1-3 目前，尚不清楚为什么大部分接种疫苗的人似乎对 SARS-CoV-2 易感，尽管宿主因素（例如，潜在的慢性疾病或遗传易感性）和病毒因素（例如，高病毒载量暴露、特定的病毒变体）都可能发挥作用。尽管这些试验纳入了近 100 000 名参与者，但肝病患者的数据极其有限（面板）。在辉瑞疫苗接种研究中，37 706 名参与者中有 217 名（0·6%）患有肝病，只有 3 名（< 0·1%）患有中度至重度肝病。 Moderna 试验中纳入的肝病患者比例也同样较低（30 351 例中的 196 例 [0·6%]）。 ChAdOx1-nCoV-19 疫苗试验明确排除了已有肝脏病理的患者。值得注意的是，在每项研究中用于分类肝病及其严重程度的标准仍不清楚。此外，所有试验都将全身免疫抑制列为排除标准，从而防止将数据外推至免疫抑制的肝移植受者或患有自身免疫性肝病的患者。此外，尽管在 12021 名接受 ChAdOx1-nCoV-19 的参与者中只有一名报告了肝脏生化异常，但有关肝脏安全性的详细细节仍未发表。丙型肝炎病毒 (HCV) ChAd 疫苗此前已安全地用于少数非肝硬化慢性 HCV 感染患者。 4 然而，对 SARS-CoV-2 疫苗安全性和肝病患者免疫反应的详细了解
Since the onset of the COVID-19 pandemic, SARS-CoV-2 vaccine development has progressed at an unprecedented rate, with recent phase 3 trial data offering the tantalising prospect of achieving herd immunity. 1–3 Until now, researchers have focused on the contribution of specific liver disease phenotypes, including transplantation and immunosuppression, to COVID-19 susceptibility and outcome. However, the hepatology community must now urgently turn its attention to characterising SARS-CoV-2 vaccine responses in these vulnerable patient groups. The Pfizer/BioNTech BNT162b2 mRNA, Moderna mRNA-1273, and the AstraZeneca/University of Oxford ChAdOx1-nCoV-19 chimpanzee adenovirus (ChAd) vector vaccines have each reported excellent safety profiles, marked efficacy in preventing symptomatic COVID-19 (62–95%), and have all gained rapid regulatory approval. 1–3 Currently, it remains unclear why a significant minority of those vaccinated appear susceptible to SARS-CoV-2, although both host factors (eg, underlying chronic diseases or genetic susceptibility) and viral factors (eg, high viral load exposure, specific viral variants) are likely to have a contributory role.Despite the inclusion of nearly 100 000 participants in these trials, data for patients with liver disease are extremely limited (panel). In the Pfizer vaccination study, 217 (0· 6%) of 37 706 participants had liver disease, and only three (< 0· 1%) had moderate to severe liver disease. A similarly low proportion of patients with liver disease were included in the Moderna trial (196 [0· 6%] of 30 351). The ChAdOx1-nCoV-19 vaccine trial explicitly omitted patients with pre-existing liver pathology. Notably, in each study the criteria used to classify liver disease and its severity remain unclear. In addition, all trials listed systemic immunosuppression as an exclusion criterion, thus preventing extrapolation of the data to immunosuppressed liver transplant recipients or patients with autoimmune liver disease. Furthermore, granular detail regarding liver safety profiles remains largely unpublished, although abnormal liver biochemistry was reported in only one of 12 021 participants receiving ChAdOx1-nCoV-19. ChAd vaccines for hepatitis C virus (HCV) have previously been safely given to a small number of patients with noncirrhotic chronic HCV infection. 4 However, a detailed understanding of SARS-CoV-2 vaccine safety and the immunological response in patients with liver disease