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急性重症自身免疫性肝炎皮质类固醇反应的早期预测因素:一项全国多中心研究。

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study.

机构信息

Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, Madrid, Spain.

Liver Unit, Hospital Clínic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Barcelona, Barcelona, Spain.

出版信息

Aliment Pharmacol Ther. 2022 Jul;56(1):131-143. doi: 10.1111/apt.16926. Epub 2022 Apr 25.

Abstract

BACKGROUND AND AIMS

To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids.

METHODS

This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis.

RESULTS

Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1).

CONCLUSION

Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.

摘要

背景和目的

评估皮质类固醇是否能改善 AIH 相关自身免疫性肝炎(AS-AIH)患者的预后,并确定治疗开始时和治疗期间的预测因素对皮质类固醇反应的预测价值。

方法

这是一项回顾性队列研究,纳入了 2002 年 1 月至 2019 年 1 月期间,来自 13 个三级中心的所有 AS-AIH 患者。复合主要结局为入院后 90 天内死亡或肝移植。采用 Kaplan-Meier 和 Cox 回归方法进行数据分析。

结果

纳入 242 例连续患者(平均年龄[标准差]49.7[16.8]岁),其中 203 例接受了皮质类固醇治疗。90 天无移植存活率总体为 61.6%(95%置信区间[CI]55.4-67.7)。皮质类固醇降低了不良结局的风险(调整后的危险比[HR]0.25;95%CI 0.2-0.4),但治疗失败率为 30.5%。由治疗开始时的年龄较大、MELD、肝性脑病和腹水组成的内部验证列线图,准确预测了皮质类固醇的反应(C 指数 0.82;[95%CI 0.8-0.9])。在应答者中,MELD 在第 3 天至第 14 天显著改善,但在无应答者中保持不变。第 7 天 MELD 的截断值为 25(灵敏度 62.5%[95%CI:47.0-75.8];特异性 95.2%[95%CI:89.9-97.8]),是反应的最佳单变量预测因子。延长皮质类固醇治疗时间并不会增加总体感染风险(调整后的 HR 0.75;95%CI 0.3-2.1)。

结论

皮质类固醇治疗开始时和治疗期间年龄较大、MELD 较高、有肝性脑病或腹水的患者,不太可能出现有利的反应,因此应避免在这些患者中延长治疗时间,特别是如果他们是移植候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c00e/9324977/fea27dfe0b3f/APT-56-131-g003.jpg

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