SAN DIEGO — In patients with severe alcohol-associated hepatitis (SAH), tapering corticosteroids appears to be safer and as effective as a conventional fixed dose, according to new research.
“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.
“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Assessing Tapered Doses
In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.
While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.
The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.
The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.
The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.
Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.
However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.
At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).
In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).
Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.
Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.
Relapse by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.
“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.
Considering Alternative Therapies
Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.
“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”
Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.
Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal told Medscape Medical News. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.
“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”
Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape Medical News, MDedge, and WebMD.
