Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.
J Viral Hepat. 2021 Feb;28(2):400-409. doi: 10.1111/jvh.13441. Epub 2020 Nov 29.
Although glucocorticoids have been used for immunosuppression of patients with primary hepatitis B virus (HBV) infection-induced severe hepatitis, the treatment is associated with a high frequency of adverse events. We conducted a pilot study for evaluating the efficacy and safety of abatacept, a cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4), for acute hepatitis B. Five patients with severe acute hepatitis B (prothrombin activity ≤ 60%) were treated for immunosuppression by abatacept. Four patients received abatacept concurrently with methylprednisolone, and another patient was treated with abatacept alone. Rapid decrease in serum alanine aminotransferase levels, increase in prothrombin activity and improvement of general condition were obtained in four out of five patients. The patient with the most severe hepatitis underwent liver transplantation due to exacerbation of hepatitis in spite of treatment with both abatacept and methylprednisolone. None of the patients developed significant adverse events associated with the use of abatacept. Hepatitis B surface antigen (HBsAg) became negative in all five patients. The effect of abatacept and methylprednisolone for severe hepatitis B was compared using a mouse model. Rapid reduction in mouse serum HBV DNA and human albumin levels and elevation of serum interferon-gamma and granzyme A levels were observed in HBV-infected human hepatocyte-transplanted immunodeficient mice that were administered human peripheral blood mononuclear cells. These hepatocyte injuries were inhibited to a greater extent by abatacept compared to methylprednisolone. Abatacept might be an effective therapy alternative to methylprednisolone to reduce acute massive liver damage for patients with severe acute hepatitis caused by HBV infection.
虽然糖皮质激素已被用于抑制原发性乙型肝炎病毒（HBV）感染引起的重型肝炎患者的免疫反应，但该治疗方案与较高的不良事件发生率相关。我们开展了一项初步研究，旨在评估 CTLA-4 免疫球蛋白（CTLA4）巴利昔单抗在急性乙型肝炎中的疗效和安全性。5 例重型乙型肝炎（凝血酶原活动度≤60%）患者接受巴利昔单抗免疫抑制治疗。4 例患者同时接受巴利昔单抗和甲泼尼龙治疗，另 1 例患者单独接受巴利昔单抗治疗。5 例患者中有 4 例迅速降低血清丙氨酸氨基转移酶水平，增加凝血酶原活动度和改善一般状况。乙型肝炎病情最严重的患者因尽管接受了巴利昔单抗和甲泼尼龙治疗但肝炎仍恶化而接受了肝移植。所有患者均未出现与巴利昔单抗使用相关的严重不良事件。5 例患者的乙型肝炎表面抗原（HBsAg）均转为阴性。我们使用小鼠模型比较了巴利昔单抗和甲泼尼龙对乙型肝炎的治疗效果。在接受人外周血单个核细胞治疗的乙型肝炎病毒感染的人肝细胞移植免疫缺陷小鼠中，观察到血清 HBV DNA 和人白蛋白水平迅速降低，血清干扰素-γ和颗粒酶 A 水平升高。与甲泼尼龙相比，巴利昔单抗能更大程度地抑制肝细胞损伤。巴利昔单抗可能是治疗乙型肝炎感染引起的重型肝炎患者急性大量肝损伤的有效替代疗法。
