High-Risk ACLF: Should Antifungal Therapy Start Before Infection Is Proven?: AJG | September 2026

What Did the Study Find?

This pragmatic RCT randomized 216 hospitalized patients with ACLF and predefined risk factors for invasive fungal infection (IFI) to immediate empirical antifungal therapy or diagnostic/biomarker-driven treatment.

28-day survival was 35% vs 13%, favoring empirical therapy.

Empirical treatment was associated with a 36% lower hazard of death (HR 0.64).

IFI resolution was substantially higher: 46% vs 23%.

In-hospital and IFI-attributable mortality were also significantly reduced.

Importantly, patients were carefully selected for high IFI risk; this was not universal antifungal prophylaxis.

Both strategies incorporated biomarkers, cultures and antifungal stewardship.

Why Does It Matter?

In critically ill ACLF patients, waiting for microbiological confirmation of fungal infection may delay potentially life-saving treatment.

GastroAGI Takeaway

This is potentially practice-changing for carefully selected high-risk ACLF patients. The trial supports early empirical antifungal therapy when predefined IFI risk is high—but not routine antifungal treatment for every patient with ACLF. Local fungal epidemiology, resistance patterns and stewardship remain essential.