Invasive Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure Patients: Short-Term Outcomes and Antifungal Options

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). 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. 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. 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.