Division of Public Health, Center for Community Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi, Japan.
Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Clin Rheumatol. 2022 Oct;41(10):3125-3133. doi: 10.1007/s10067-022-06278-w. Epub 2022 Jul 7.
INTRODUCTION/OBJECTIVES: Serum alanine aminotransferase (ALT) elevation is considered a risk factor for resistance to initial intravenous immunoglobulin (IVIG) treatment in patients with Kawasaki disease (KD). However, serum ALT levels change dramatically during acute KD illness. We tested the hypothesis that risk assessment for initial IVIG resistance based on serum ALT elevation may differ by examination day after KD onset.
We analyzed 18,492 population-based patients who developed KD throughout Japan. First, we epidemiologically evaluated the serum ALT variation at 1‒10 days after disease onset. Second, we conducted multivariable logistic regression to determine the association between serum ALT level and initial IVIG resistance according to timing of initial hospital visit by stratifying the patients into an early group (1‒5 days after onset) and a late group (6‒10 days after onset).
Serum ALT rapidly increased after KD onset, peaked at day 4 of illness, and then declined regardless of IVIG responsiveness. The adjusted odds ratio (OR) increased with increasing serum ALT in the early group (adjusted OR [95% CI]: 1.44 [1.25-1.66], 1.94 [1.65-2.28], and 2.22 [1.99-2.48] for serum ALT 50-99, 100-199, and ≥ 200 IU/L, respectively; reference ALT level: 1-49 IU/L). No significant association was observed in the late group.
The findings indicate that risk assessment for initial IVIG resistance based on serum ALT level may only be reliable for patients with KD who visit hospitals during early illness, specifically 1-5 days after disease onset. Key Points Serum alanine aminotransferase level differed markedly according to examination days after Kawasaki disease onset. Serum alanine aminotransferase level declined toward normal range after day 5 of illness regardless of intravenous immunoglobulin responsiveness. Elevated serum alanine aminotransferase level was no longer a significant risk factor for initial intravenous immunoglobulin resistance when measured on delayed hospital visits. Risk assessment for initial intravenous immunoglobulin resistance based on serum alanine aminotransferase level may only be reliable for patients who visit hospitals during early illness, specifically 1-5 days after disease onset.
介绍/目的：血清丙氨酸氨基转移酶（ALT）升高被认为是川崎病（KD）患者对初始静脉注射免疫球蛋白（IVIG）治疗产生耐药的危险因素。然而，血清 ALT 水平在 KD 急性发病期间会发生显著变化。我们检验了这样一个假设，即在 KD 发病后不同时间点，基于血清 ALT 升高的初始 IVIG 耐药风险评估可能存在差异。
我们分析了日本全国各地 18492 例发生 KD 的患者。首先，我们对发病后 1-10 天的血清 ALT 变化进行了流行病学评估。其次，我们通过将患者分为早期组（发病后 1-5 天）和晚期组（发病后 6-10 天），根据首次就诊的时间进行多变量逻辑回归，确定血清 ALT 水平与初始 IVIG 耐药之间的关系。
血清 ALT 在 KD 发病后迅速升高，在发病第 4 天达到峰值，随后无论 IVIG 反应如何均呈下降趋势。在早期组中，随着血清 ALT 的升高，调整后的比值比（OR）也随之增加（调整后的 OR [95%CI]：血清 ALT 50-99、100-199 和≥200IU/L 分别为 1.44 [1.25-1.66]、1.94 [1.65-2.28] 和 2.22 [1.99-2.48]；参考 ALT 水平：1-49IU/L）。晚期组未见明显相关性。
研究结果表明，基于血清 ALT 水平评估初始 IVIG 耐药的风险，仅适用于在疾病早期（发病后 1-5 天）就诊的 KD 患者。
血清丙氨酸氨基转移酶水平在 KD 发病后不同时间点差异显著。
无论 IVIG 反应如何，血清 ALT 水平在发病后第 5 天开始向正常范围下降。
在延迟就诊时，升高的血清丙氨酸氨基转移酶水平不再是初始静脉免疫球蛋白耐药的显著危险因素。
基于血清丙氨酸氨基转移酶水平评估初始 IVIG 耐药的风险，仅适用于在疾病早期（发病后 1-5 天）就诊的患者。
