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.