Introduction

Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA).

Methods

ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts.

Results

ACLF patients with probable IPA (n = 145) had greater 28-day mortality (33.6% vs. 15.7%, p < 0.001) than those without (n = 383). The respiratory failure-associated 28-day mortality was greater in ACLF patients with IPA than in those without before (17.1% vs. 0.3%, p < 0.001) and after (16.0% vs. 0.0%, p < 0.001) propensity score matching in 116 pairs. IPA patients with lung injury had greater 28-day all-cause mortality (66.5% vs. 24.2%, p < 0.001) and IPA-associated mortality (45.8% vs. 8.1%, p < 0.001) than patients without lung injury (PaO2/FiO2 ≥ 400 mmHg). Antifungal therapy was prescribed to 139 of 145 patients, and 102 patients were treated with voriconazole alone (n = 59) or sequential/combined therapy (n = 43) with varying loading doses (100–800 mg) and daily maintenance doses (0–800 mg). A proposed optimal voriconazole regimen (loading dose, 200 mg twice daily; daily maintenance dose, 100 mg) achieved comparable short-term survival and optimal trough drug concentrations (1–5 μg/mL) on therapeutic drug monitoring in 26 patients.

Conclusion

Presence of IPA increases the short-term mortality of ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients.

中文翻译：

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急性慢性肝衰竭患者的侵袭性肺曲霉病：短期结果和抗真菌选择

介绍

急性慢性肝功能衰竭 (ACLF) 患者易受侵袭性真菌感染。我们评估了侵袭性肺曲霉病 (IPA) 的 ACLF 患者的预后和抗真菌选择。

方法

回顾性筛选了 2011 年至 2018 年来自 15 家医院的 IPA 的 ACLF 患者，从前瞻性队列（NCT02457637）中纳入了 383 名无肺部感染的 ACLF 患者。在两个队列中记录了人口统计学、实验室、临床数据和 28 天的结果。

结果

可能患有 IPA 的 ACLF 患者 ( n  = 145) 的 28 天死亡率（33.6% 对 15.7%，p  < 0.001）高于未患 IPA 的患者( n  = 383)。有 IPA 的 ACLF 患者的呼吸衰竭相关 28 天死亡率高于没有 IPA 前（17.1% 对 0.3%，p  < 0.001）和后（16.0% 对 0.0%，p  < 0.001）倾向评分匹配的患者116 对。IPA 肺损伤患者的 28 天全因死亡率更高（66.5% 对 24.2%，p  < 0.001）和 IPA 相关死亡率（45.8% 对 8.1%，p < 0.001) 比没有肺损伤的患者 (PaO2/FiO2 ≥ 400 mmHg)。145 名患者中的 139 名接受了抗真菌治疗，102 名患者接受了单独使用伏立康唑 ( n  = 59) 或序贯/联合治疗 ( n  = 43) 和不同负荷剂量 (100–800 mg) 和每日维持剂量 (0– 800 毫克）。建议的最佳伏立康唑方案（负荷剂量，每天 2 次，每次 200 毫克；每日维持剂量，100 毫克）在 26 名患者的治疗药物监测中实现了相当的短期存活率和最佳的药物谷浓度（1-5 微克/毫升）。

结论

IPA 的存在增加了 ACLF 患者的短期死亡率，主要是由于呼吸衰竭。此类危重患者需要最佳伏立康唑方案。