STASH Trial

The STASH trial (Short for "Steroid Tapering in Severe Alcohol-associated Hepatitis") was a multicenter, open-label randomized clinical trial aimed at evaluating the efficacy and safety of a tapered prednisolone regimen compared to the standard fixed-dose regimen in patients with severe alcohol-associated hepatitis (AAH). The trial was conducted to address concerns about the high risk of infections associated with corticosteroid treatment in AAH patients, while still preserving its therapeutic benefits.

Background:

Severe AAH is a life-threatening condition characterized by liver inflammation due to excessive alcohol consumption. Corticosteroids, such as prednisolone, are the standard treatment for severe AAH because they reduce liver inflammation and improve short-term survival. However, corticosteroids suppress the immune system, leading to a high risk of secondary infections, which can worsen patient outcomes. Clinical guidelines recommend a fixed daily dose of 40 mg prednisolone for 28 days, but there has been ongoing debate about whether a tapering regimen could reduce infection risks while maintaining efficacy.

Study Design:

• Study Period: March 2023 to August 2024.
• Participants: 254 adults diagnosed with severe AAH.
• Intervention Groups:

1. Fixed-dose group: Participants received 40 mg/day of prednisolone for 28 days (standard regimen).

2. Tapered-dose group: Participants received a four-week tapering regimen of prednisolone (gradual dose reduction over 28 days).

• Primary Endpoint: Incidence of infections by day 90, assessed using standardized criteria.
• Secondary Endpoints: Mortality at day 90, transplant-free survival, liver function improvement (measured by MELD score), rates of acute kidney injury (AKI), and overall adverse events.

Key Findings:

1. Infection Risk:

• Tapered-dose group had significantly fewer infections by day 90 compared to the fixed-dose group (19.7% vs. 33.1%).
• Microbiologically confirmed infections were also reduced in the tapered-dose group.
• The most common infections were lung infections, followed by urinary and peritoneal infections.

2. Mortality and Survival:

• Despite the reduction in infection rates, there was no significant difference in day-90 mortality or transplant-free survival between the two groups.

3. Liver Function and AKI:

• Both groups showed similar improvements in liver function (MELD score) and comparable rates of acute kidney injury.

4. Adverse Events:

• Overall adverse events and hospitalizations were more frequent in the fixed-dose group, suggesting a safety advantage with the tapering regimen.

Conclusion:

The STASH trial demonstrated that a tapered prednisolone regimen significantly reduces the risk of infections in patients with severe AAH compared to the standard fixed-dose regimen. Importantly, this reduction in infection risk was achieved without compromising short-term survival or liver function improvement. These findings suggest that tapering corticosteroids is a safer and more effective strategy for managing severe AAH, addressing the long-standing challenge of balancing immunosuppression with infection risk.

Implications:

The results of the STASH trial could lead to a revision of current clinical guidelines for the treatment of severe AAH, favoring a tapered prednisolone regimen over the fixed-dose approach. This approach may improve patient safety and outcomes by minimizing secondary infections, which are a major cause of morbidity and mortality in this population.