We have read with interest the study published by Palla et al.^[1] regarding a possible link between COVID-19 vaccination and the development of autoimmune hepatitis (AIH).^{[2, 3]} We propose the need for population-based studies to gather data on the incidence, severity, and clinical features of COVID-19 vaccination-induced AIH by describing three cases of COVID-19 vaccination-induced AIH from our institution between January and October 2021.

Case 1 involves an 80-year-old woman diagnosed with a liver injury (aspartate aminotransferase 995 U/L, alanine aminotransferase 974 U/L, total bilirubin 3.5 mg/dl), based on her laboratory results 10 days after receiving the second dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. The antinuclear antibody test was positive at a titer of 1:40. The serum immunoglobulin G level was 1936 mg/dl. A full serological screen excluded other causes of acute liver disease. Liver biopsy revealed lymphoplasmacytic infiltration in the portal area with moderate interface hepatitis, compatible with AIH (Figure 1A,B). She was treated with prednisone at an initial dose of 0.8 mg/kg/day. The dose was subsequently tapered to 10 mg/week on noting progressive improvement in her laboratory results (Figure 1C).

Two other patients exhibited similar findings. One was a 75-year-old woman who developed AIH 4 days after the second dose of BNT162b2, whereas the other was a 78-year-old woman who developed AIH 7 days after her first dose of BNT162b2. The histological features of the liver biopsy specimen and the clinical course of the two patients are presented in Figures S1 and S2. The clinical characteristics of the patients are presented in Table S1. All 3 patients underwent regular blood testing because of underlying diseases without anterior liver injury.

Epidemiological studies on post-COVID-19 vaccination myocarditis have shown that most cases occurred within 1 month of vaccination.^[4] This was consistent with the three reported cases. Approximately 0.9 million people had received two vaccine doses in our medical region by October 31, 2021. Therefore, the incidence of AIH due to COVID-19 vaccination was estimated to be three cases per million people. When managing new or exacerbated AIH cases, the patient’s COVID-19 vaccination history should be investigated. Rigorous population-based studies are required in the future to evaluate the incidence of COVID-19 vaccine–induced AIH.

我们感兴趣地阅读了 Palla 等人发表的研究。^{[ 1 ]}关于 COVID-19 疫苗接种与自身免疫性肝炎 (AIH) 发展之间可能存在的联系。^{[ 2, 3 ]}我们建议需要进行基于人群的研究，以收集关于 COVID-19 疫苗接种诱导的 AIH 的发生率、严重程度和临床特征的数据，方法是描述我们机构在2021 年 1 月和 10 月。

病例 1 涉及一名 80 岁女性，根据接受第二剂 10 天后的实验室结果，诊断为肝损伤（天冬氨酸氨基转移酶 995 U/L，丙氨酸氨基转移酶 974 U/L，总胆红素 3.5 mg/dl） BNT162b2（辉瑞-BioNTech）COVID-19疫苗。抗核抗体试验呈阳性，滴度为 1:40。血清免疫球蛋白 G 水平为 1936 mg/dl。全面的血清学筛查排除了急性肝病的其他原因。肝活检显示门区淋巴浆细胞浸润伴中度界面性肝炎，符合 AIH（图 1A，B）。她接受了泼尼松治疗，初始剂量为 0.8 mg/kg/天。由于注意到她的实验室结果逐渐改善，剂量随后逐渐减少到 10 毫克/周（图 1C）。

另外两名患者表现出类似的发现。一名 75 岁女性在第二剂 BNT162b2 后 4 天出现 AIH，而另一名 78 岁女性在第一剂 BNT162b2 后 7 天出现 AIH。肝活检标本的组织学特征和两名患者的临床病程如图 S1 和 S2 所示。患者的临床特征见表S1。3例患者均因基础疾病定期验血，无前部肝损伤。

对 COVID-19 疫苗接种后心肌炎的流行病学研究表明，大多数病例发生在接种疫苗后 1 个月内。^{[ 4 ]}这与报告的三个案例一致。到 2021 年 10 月 31 日，我们的医疗区域约有 90 万人接种了两剂疫苗。因此，由于 COVID-19 疫苗接种导致 AIH 的发病率估计为每百万人 3 例。在管理新的或加重的 AIH 病例时，应调查患者的 COVID-19 疫苗接种史。未来需要进行严格的基于人群的研究来评估 COVID-19 疫苗诱导的 AIH 的发病率。