Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure
Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure
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DOI：
10.1007/s00535-017-1306-5
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发表时间：
2017-08-01
影响因子：
6.3
通讯作者：
Takikawa, Yasuhiro
中科院分区：
文献类型：
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作者：
Kakisaka, Keisuke;Kataoka, Kojiro;Takikawa, Yasuhiro
在日本，急性肝损伤（ALI）/急性肝衰竭（ALF）患者通常使用皮质类固醇治疗以预防肝性脑病的发生，但尚未确定开始皮质类固醇治疗的适当时机，也未进行治疗的最佳疗效评价。我们前瞻性研究了根据已确定的严重程度适应症开始治疗的最佳时机：日本肝性脑病预测模型（JHEPM）和凝血酶原时间（PT）。这项前瞻性观察性研究从2004年至2015年招募了469例ALI/ALF患者。我们评估了44例ALF患者在肝昏迷发生前接受大剂量皮质类固醇治疗。在给予大剂量皮质类固醇治疗前一天，使用PT和JHEPM概率的受试者操作曲线法评估昏迷发展的预测性能。采用倾向评分法校正选择偏倚。高剂量皮质类固醇治疗倾向于降低昏迷发展的风险，尽管没有统计学意义。JHEPM概率、PT-国际标准化比值（PT-INR）和PT活性的临界值分别为53%、1.95和39%，具有较高的敏感性和特异性。JHEPM概率为40%，PT-INR为1.53，PT为52%，因为这些值理论上可在98%的范围内区分昏迷患者。由于该研究存在选择偏倚，因此应在未来的前瞻性研究中确认适当的治疗时机。
Corticosteroid therapy has been commonly administered to patients with acute liver injury (ALI)/acute liver failure (ALF) in Japan to prevent the development of hepatic encephalopathy, but the appropriate timing to start corticosteroid therapy has not been determined and optimal response evaluation of the therapy has not been conducted. We prospectively investigated the optimal timing to start therapy on the established severity indication: the Japan Hepatic Encephalopathy Prediction Model (JHEPM) and prothrombin time (PT).This prospective observational study enrolled 469 patients with ALI/ALF from 2004 to 2015. We evaluated 44 patients with ALF on high-dose corticosteroid therapy before hepatic coma development. The predictive performance for coma development was assessed using the receiver operator curve method in both PT and JHEPM probability the day before administering high-dose corticosteroid therapy.Among these patients, nine developed hepatic coma after the therapy. Selection bias was adjusted using propensity score method. High-dose corticosteroid therapy tended to decrease the risk of coma development although there was no statistical significance. The cut-off value of 53%, 1.95, and 39% in JHEPM probability, PT-international normalized ratio (PT-INR), and PT activity, respectively, showed high sensitivity and specificity.We propose the appropriate timing to start high-dose corticosteroid therapy in patients with ALI/ALF; 40% of JHEPM probability, 1.53 of PT-INR, and 52% of PT because these values were theoretically discriminated at 98% coverage to the patients with coma. Because the study contained selection bias, the appropriate timing for therapy should be confirmed in a future prospective study.