Infections in Standard or Tapered Dose of Prednisolone for Alcohol-Associated Hepatitis: A Randomized Trial (STASH Trial)
Anand V. Kulkarni, Karan Kumar, Suprabhat Giri, Juan Pablo Arab, Shantan Venishetty, Madhumita Premkumar, Harshith B. Kadnur, Mithun Sharma, Manasa Alla, Sowmya Iyengar, Gauri Nayak, Vivek A. Saraswat, Rajesh Gupta, Padaki Nagaraja Rao, K. Rajender Reddy, D. Nageshwar Reddy
Abstract
INTRODUCTION: Current guidance recommends a 40-mg dose of prednisolone (or equivalent) for severe alcohol-associated hepatitis (AAH), while infections are not uncommon in them. The benefits of a rapid prednisolone tapering regimen in mitigating infection in patients with AAH are unknown. The primary objective was to assess the incidence of infection by day 90. The key secondary objectives were the incidence of mortality, acute kidney injury, readmissions rate, and adverse events. METHODS: In this multicenter randomized clinical trial, patients with severe AAH were included from March 15, 2023, to August 28, 2024. Patients were randomly assigned to receive a standard fixed prednisolone dose (40 mg/d) for 4 weeks or 40 mg/d tapered by 10 mg/d every week over 4 weeks. RESULTS: Two hundred fifty-four patients were enrolled (age: 41.16 ± 8.2 years, 98% men). The incidence of infection on day 90 was 33.1% (42 of 127; 95% confidence interval [CI] 23.8-44.7) in the fixed-dose group compared with 19.7% (25 of 127; 95% CI 16.1-37) in the tapered dose group, with a hazard ratio of 0.57 (95% CI 0.35-0.94; P = 0.03). On competing risk regression analysis after adjustment for relevant covariates, tapered dose of prednisolone was associated with a lower incidence of infection by day 90 (subdistribution hazard ratio 0.34; 95% CI 0.15-0.78; P = 0.01). Nineteen percent (24/127; 95% CI 12.5-26.8) in the fixed-dose group and 8.6% (11/127; 95% CI 4.4-14.9; P = 0.02) in the tapered-dose group had microbiologically proven infections. There were no differences in mortality, acute kidney injury incidence, hospitalizations, or all-cause adverse events. DISCUSSION: In patients with severe AAH, a tapered prednisolone regimen may mitigate the frequency of infections (CTRI/2023/03/050521).