Larsucosterol for the Treatment of Alcohol-Associated Hepatitis

作者：Mitchell Shiffman, Ben L. Da, Aparna Goel, Allison J. Kwong, Lance L. Stein, Christophe Moreno, Amanda Nicoll, Ashwini Mehta, Alexandre Louvet, Steven L. Flamm, Nikolaos Pyrsopoulos, Sanjaya K. Satapathy, Alexander Kuo, Daniel Ganger, Costica Aloman, Simone I. Strasser, Edmund C. M. Tse, Mark W. Russo, Don C. Rockey, Meagan Gray, Mack C. Mitchell, Mark Thursz, William Krebs, Deborah Scott, Christina Blevins, David J. Ellis, James Brown, Norman Sussman, WeiQi Lin · 发表于：NEJM Evidence · 年份：2025 · DOI：10.1056/evidoa2400243 · 被引用次数：8 · 研究领域：Alcohol Consumption and Health Effects、Liver Disease Diagnosis and Treatment、Drug-Induced Hepatotoxicity and Protection

BACKGROUND: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy. METHODS: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators. Patients in the placebo group, if prescribed, received 32 mg of methylprednisolone, while patients in the larsucosterol groups received matching placebo capsules. The primary end point was 90-day mortality or liver transplant (LT) rate. The key secondary end point was 90-day mortality. We prespecified the reporting of U.S. results separately. RESULTS: Among 307 enrolled patients, 301 received at least one treatment dose. The difference in 90-day mortality or LT between the 30-mg or 90-mg larsucosterol and placebo groups did not reach statistical significance. Ninety-day mortality in the placebo and the 30-mg and 90-mg groups was 25 out of 103, 15 out of 102, and 17 out of 102, respectively. Among U.S. patients (76% of all enrolled patients), there were 21 deaths and 4 LTs among 77 patients in the placebo group, 8 deaths and 5 LTs among 73 patients in the 30-mg larsucosterol group, and 10 deaths and 8 LTs among 77 patients in the 90-mg larsucosterol group. In patients who were treated within less than 10 days of hospitaliza...