Empirical Antifungal Therapy Improves Survival in Patients With Acute-on-Chronic Liver Failure With Suspected Invasive Fungal Infections: A Pragmatic Randomized Trial.

In 30 seconds

This pragmatic, parallel-group randomized trial compared empirical antifungal therapy at enrolment with diagnostic- or biomarker-driven pre-emptive therapy in 216 hospitalized patients with acute-on-chronic liver failure (ACLF) and predefined risk factors for invasive fungal infection. Both groups received stewardship protocols. Empirical therapy improved 28-day survival: 35% vs 13% (hazard ratio: 0.64, 95% confidence interval: 0.47-0.88; P = 0.005). Treatment success and infection resolution were also higher, while in-hospital and infection-attributable mortality were lower in the empirical group.

Key findings

• 28-day survival was 35% with empirical therapy versus 13% with diagnostic/biomarker-driven pre-emptive therapy (hazard ratio: 0.64, 95% confidence interval: 0.47-0.88; P = 0.005).
• Treatment success was 37.4% vs 16.9% (P = 0.002), and invasive fungal infection resolution was 45.8% vs 22.5% (P = 0.001).
• In-hospital and infection-attributable mortality was lower with empirical therapy (55.6% vs 75.9%; P = 0.003).
• The reported survival benefit was greatest among patients aged 40 years or older with cardiovascular failure but without respiratory failure.

Why it matters

Invasive fungal infection in ACLF is associated with substantial mortality, yet the optimal timing of antifungal treatment is uncertain. This randomized comparison suggests that starting empirical therapy in selected high-risk hospitalized patients may improve short-term survival when paired with structured diagnostic and stewardship protocols. The findings highlight the potential importance of timely treatment while retaining diagnostic oversight.

What to keep in mind

The trial was conducted in a high-burden setting, which may limit applicability to settings with different invasive fungal infection prevalence or resources.