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Tapering doses of corticosteroids was safer than, and just as effective as, a fixed dose in patients with severe alcohol-associated hepatitis, a randomized trial showed.

Patients who received a tapered dose of prednisolone starting at 40 mg and reduced by 10 mg weekly over the course of 4 weeks compared with a fixed dose of prednisolone 40 mg for 4 weeks experienced fewer infections (25 vs 42) and were hospitalized less frequently (33% vs 44.1%) at 90 days, reported Anand Kulkarni, MBBS, of the Asian Institute of Gastroenterology in Hyderabad, India.

Tapering prednisolone also reduced the risk of all-cause adverse events compared with a fixed dose (48.8% vs 60%). Frequent adverse events included acute kidney injury (18.9% vs 26.8%, respectively), hepatic encephalopathy (6.3% vs 11.8%), hyperglycemia (3.9% vs 7.1%), and hematochezia (4.7% vs 6.3%).

Tapering had no effect on overall survival, nor on Model for End-Stage Liver Disease (MELD) score, Kulkarni said during a late-breaking abstract session at the American Association for the Study of Liver Diseases annual meeting in San Diego.

Severe alcohol-associated hepatitis has a mortality rate of 20%-30% at 90 days. While the use of corticosteroids has been standard of care in these patients, infection is a major concern.

According to Kulkarni, there have been no large randomized trials assessing the optimal dose of corticosteroids, "and it is unknown whether stepwise tapering of corticosteroids reduces the risk of infection."

This multicenter, open-label trial included 254 patients from four Indian centers and one Canadian center who were randomized 1:1 to the tapering group or the fixed dose group. Across the two groups, mean age was 41-42 years, 98-99% were men, and mean MELD score was 25.3 to 26.

The average daily corticosteroid dose was 28.4 mg in the tapered dose group and 40.8 mg in the fixed dose group, and the proportion of steroid responders (defined as a Lille's score <0.45) was similar between groups (82.5% vs 80.3%). Fifty-five percent of patients in the tapered group received prophylactic antibiotics during corticosteroid therapy compared with 66% of the fixed dose group.

In both groups, the most common type of infection was lung infection, followed by urinary tract infections, and median time to infection was 30 days. Average durations of hospitalization were 5.44 days in the tapered group and 6.31 days in the fixed dose group.

The mortality rate at day 90 was 13.4% in the tapering group versus 16.5% in the fixed dose group, with the most common cause of death being sepsis with multiple organ failure in both groups.

The mean MELD scores at day 90 were 16 in the tapering group and 17 in the fixed dose group, and the percentages of patients with a MELD score <17 at day 90 were 58.9% and 56.6%, respectively -- both insignificant differences.

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