Recently, in the Liver International, Marabotto et al,¹ reported a patient who developed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID-19). Here, we present two patients who developed high aminotransferases during COVID-19 and were ultimately diagnosed with AIH.

The general characteristics and outcome of these patients are summarized in Table 1. COVID-19 was diagnosed by PCR-based test. Serologies for acute and chronic viral hepatitis (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, anti-EBV IgM and anti-CMV IgM) were all negative. AIH was diagnosed by the presence of positive autoimmune serology and high serum IgG levels. Immunosuppressive therapy was given during active COVID-19 to one patient but was delayed until the COVID-PCR test became negative in the other patient. Both patients showed good response to immunosuppressive therapy at the time of writing this paper.

New-onset or flare of immune-mediated disorders such as Guillain-Barre syndrome, autoimmune haemolytic anaemia and immune thrombocytopenic purpura has been described during or following COVID-19.² These reports suggest that COVID-19 can break immunological tolerance and lead to the onset of immune-mediated conditions. Serum levels of TNF-α, IFN-γ, IL-1β, IL-6 and IL-10 are increased in patients with COVID-19.² These cytokines have also critical roles in the inflammatory process of AIH. Therefore, it is reasonable to think that COVID-19 can cause new-onset or flare of silent AIH.

Drug-induced liver injury (DILI) may present with laboratory and serological features of AIH. Patient 1 was treated with hydroxychloroquine and favipravir for COVID-19. With the suspicion of DILI, immunosuppressive therapy was discontinued after three months of biochemical remission. He, however shortly displayed signs of biochemical relapse (elevated aminotransferases and IgG levels). After reinstitution of immunosuppression he again entered remission. This outcome strongly suggests that the diagnosis was indeed AIH rather than DILI. Patient 2 developed high aminotransferases levels during COVID-19 without any suspicion of DILI.

There is no evidence-based diagnostic algorithm or treatment recommendation for AIH in active COVID-19 patients.^{3, 4} Some experts suggest that an AIH diagnosis can be made without liver biopsy during COVID-19 if patients have typical laboratory and serological findings.⁵ Our two patients had laboratory features strongly suggestive of AIH and we, therefore did not perform liver biopsies.

In patients with concomitant AIH and COVID-19, immunosuppressive therapy should be given after weighing potential risks and benefits. Patient 1 had mild features of AIH at presentation and therapy was delayed until COVID-19 PCR test became negative. Patient 2 had a clinically more severe form of AIH and was given immunosuppressive therapy which may be considered life-saving in severe AIH.

New-onset liver injury is a commonly observed clinical manifestation of COVID-19. Our two cases along with the report of Marabotto et al highlight that AIH should be considered among different possible diagnoses in subjects who develop elevated aminotransferases during or soon after COVID-19.

最近，在 Liver International 上，Marabotto 等人¹报道了一名患者在 2019 年冠状病毒病 (COVID-19) 期间发展为自身免疫性肝炎 (AIH)。在这里，我们介绍了两名在 COVID-19 期间出现高转氨酶并最终被诊断为 AIH 的患者。

这些患者的一般特征和结果总结在表 1 中。 COVID-19 是通过基于 PCR 的测试诊断出来的。急性和慢性病毒性肝炎的血清学（抗 HAV IgM、HBsAg、抗 HBc IgM、抗 HCV、抗 EBV IgM 和抗 CMV IgM）均为阴性。通过自身免疫血清学阳性和高血清 IgG 水平的存在来诊断 AIH。在 COVID-19 活动期间对一名患者进行了免疫抑制治疗，但被推迟到另一名患者的 COVID-PCR 检测结果为阴性。在撰写本文时，两名患者对免疫抑制治疗均表现出良好的反应。

在 COVID-19 期间或之后描述了免疫介导的疾病的新发或突发，例如格林-巴利综合征、自身免疫性溶血性贫血和免疫性血小板减少性紫癜。²这些报告表明 COVID-19 可以破坏免疫耐受并导致免疫介导疾病的发作。COVID-19 患者的血清 TNF-α、IFN-γ、IL-1β、IL-6 和 IL-10 水平升高。²这些细胞因子在 AIH 的炎症过程中也具有关键作用。因此，有理由认为 COVID-19 会导致无症状 AIH 的新发或突发。

药物性肝损伤 (DILI) 可能具有 AIH 的实验室和血清学特征。患者 1 接受了羟氯喹和法维拉韦治疗 COVID-19。由于怀疑 DILI，在生化缓解三个月后停止免疫抑制治疗。然而，他很快就出现了生化复发的迹象（转氨酶和 IgG 水平升高）。在恢复免疫抑制后，他再次进入缓解期。这一结果强烈表明诊断确实是 AIH 而不是 DILI。患者 2 在 COVID-19 期间出现高转氨酶水平，但没有任何怀疑 DILI。

对于活动性 COVID-19 患者的 AIH，没有基于证据的诊断算法或治疗建议。^{3, 4}一些专家建议，如果患者有典型的实验室和血清学检查结果，在 COVID-19 期间无需肝活检即可做出 AIH 诊断。⁵我们的两名患者的实验室特征强烈提示 AIH，因此我们没有进行肝活检。

对于同时存在 AIH 和 COVID-19 的患者，应在权衡潜在风险和获益后给予免疫抑制治疗。患者 1 在就诊时有轻微的 AIH 特征，治疗被推迟到 COVID-19 PCR 检测呈阴性。患者 2 患有临床上更严重的 AIH，并接受了免疫抑制治疗，这在严重 AIH 中可能被认为是挽救生命的。

新发肝损伤是 COVID-19 常见的临床表现。我们的两个案例以及 Marabotto 等人的报告强调，在 COVID-19 期间或之后不久出现转氨酶升高的受试者的不同可能诊断中应考虑 AIH。