Abstract：
Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers\' vigilant monitoring and timely management.
摘要：
尽管以前的研究集中在与COVID-19疫苗相关的肝胆和胃肠道不良反应（ADR），关于其他疫苗的此类ADR的文献有限，特别是在全球范围内。因此,我们旨在调查疫苗相关肝胆和胃肠道ADR的全球负担,并确定与这些事件相关的疫苗.本研究利用世界卫生组织（WHO）国际药物警戒数据库的数据提取了1967年至2023年疫苗相关肝胆和胃肠道不良反应的报告（总报告=131255418）。通过全球报告计数，具有95%置信区间(CI)的报告优势比(ROR)，和信息成分(IC)加上IC0.25,该研究调查了156个国家的16种疫苗与肝胆和胃肠道ADR发生率之间的关联.在6842303份疫苗相关不良反应报告中，10786份肝损伤报告，927870例胃肠道症状报告，2978例胰腺和胆管损伤报告，我们发现了1967年至2023年之间的96例腹腔内出血报告.大多数肝胆和胃肠道不良反应在2020年后激增，大多数报告归因于COVID-19信使RNA（mRNA）疫苗。甲型肝炎疫苗与肝损伤的相关性最高(ROR[95%CI]:10.30[9.65-10.99];IC[IC0.25]:3.33[3.22]),其次是乙型肝炎，伤寒,和轮状病毒。具体来说,缺血性肝炎与Ad5载体和mRNACOVID-19疫苗均有显著关联.胃肠道症状与除结核疫苗外的所有疫苗有关。特别是轮状病毒（11.62[11.45-11.80];3.05[3.03]）和伤寒（11.02[10.66-11.39];3.00[2.96]）。胰腺和胆管损伤与COVID-19mRNA（1.99[1.89-2.09];0.90[0.83]）有关，MMR（麻疹，腮腺炎,和风疹)，和乳头瘤病毒疫苗。对于腹腔内出血，灭活的全病毒COVID-19疫苗（3.93[1.86-8.27]；1.71[0.41]）具有最高的相关性，其次是COVID-19mRNA（1.81[1.42-2.29]；0.77[0.39]）。这些不良反应大多发病时间短,1天内,和低死亡率。通过全球规模的数据库，大多数ADR发生在1天内，强调医护人员警惕监测和及时管理的重要性。
