Steroids Linked to Reduced Risk of Acute Kidney Injury in Severe Alcohol-Associated Hepatitis

In patients with severe alcohol-associated hepatitis (sAH), corticosteroid therapy is independently associated with a significantly decreased risk of acute kidney injury (AKI) development, according to new research.1

Findings from the post-hoc analysis of VTL-308, a phase 3, randomized, open-label, multicenter study evaluating patients with alcohol-induced liver decompensation or severe alcohol-associated hepatitis, suggest a protective effect against AKI but no impact on recovery once AKI has occurred.1,2

“Our findings suggest that early corticosteroid therapy may reduce the risk of AKI, highlighting a potential renoprotective effect beyond its known impact on liver inflammation, ” wrote study investigator Laura Buttler from the department of gastroenterology at Hannover Medical School, and colleagues.1

The study included 151 patients with sAH, diagnosed based on alcohol use ≤6 weeks before admission, consistent with alcohol-induced liver decompensation and by fulfilling either histological confirmation or ≥ 2 typical clinical features alongside a bilirubin ≥ 16 mg/dl and a Maddrey discriminant function (DF) score ≥ 3.To identify factors independently associated with the development of AKI, investigators analyzed 140 patients without AKI at baseline.1

Investigators analyzed 63 cases of AKI, classifying incidence, clinical relevance, and associated risk factors. The diagnosis of AKI was based on an acute increase of serum creatinine (sCr) ≥ 0.3 mg/dl (≥ 26.5 μmol/l) from baseline within 48 h, or a ≥ 50% increase in sCr from a known value within the prior seven days.1

Upon a competing risk analysis, investigators noted a significant association between AKI and increased mortality within 90 days. In the univariate analysis, AKI was associated with a subdistribution hazard ratio (sHR) of 9.23 (95% Confidence Interval [CI], 3.63–23.50; P < .001). This association remained robust in the multivariate model after adjustment for GAHS (sHR, 8.74; 95% CI, 3.43–22.26; P < .001).1

Cox regression analysis with time-dependent covariates confirmed the significant effect of AKI on mortality, showing an HR of 12.69 in the univariate analysis (95% CI, 4.92–32.72; P < .001) and an HR of 12.05 in the multivariate model (95% CI, 4.62–31.08; P < .001).1

In a 90-day follow-up, corticosteroids were significantly associated with a reduced risk of developing AKI. Upon competing risk analysis, investigators saw a significantly decreased risk of AKI in patients with steroid therapy compared to those without (univariate sHR, 0.49; 95% CI, 0.28–0.88; P = 0.017).1

This protective effect remained robust after adjusting for bilirubin levels in the multivariate model (sHR, 0.47; 95% CI: 0.27–0.84; P = 0.01) and after matching of patients with and without corticosteroid intake (sHR = 0.46; 95% CI, 0.25–0.85; P = 0.01). In Cox regression analysis, corticosteroid therapy was not significantly associated with AKI reversal (Hazard Ratio [HR], 1.15; 95% CI, 0.51–2.57; P = 0.74).1

“Our study identified a consistent protective association between corticosteroid therapy and AKI, a finding with potential therapeutic implications in this vulnerable population,” investigators concluded. “Therefore, our study might contribute to the initiation of future prospective trials to further investigate the association between corticosteroids and AKI development.”1

References

1. Buttler L, Stange J, Pyrsopoulos N, et al. Steroid therapy is linked to lower incidence of acute kidney injury in patients with severe alcohol-associated hepatitis. Scientific Reports. 2025;15(1). doi:https://doi.org/10.1038/s41598-025-29912-4

2. Vital Therapies, Inc. Vital Therapies Announces That Topline Results of VTL-308 Fail to Achieve Primary and Secondary Endpoints of Improvement in Survival. GlobeNewswire News Room. Published September 12, 2018. Accessed December 8, 2025. https://www.globenewswire.com/news-release/2018/09/12/1569553/31568/en/Vital-Therapies-Announces-That-Topline-Results-of-VTL-308-Fail-to-Achieve-Primary-and-Secondary-Endpoints-of-Improvement-in-Survival.html