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There were increases in fibrosis stage for 24% of patients in the rifaximin-α group, compared to 43% of the placebo group.
A team, led by Mads Israelsen, PhD, Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, compared the efficacy and safety of rifaximin-α with placebo in patients with alcohol-related liver disease.
Alcohol is currently the leading cause of liver-related deaths worldwide. It is widely known that the gut-liver axis is a driver in alcohol-related liver disease.
In addition, rifaximin-α has shown the ability to improve gut-barrier function and reduce systemic inflammation in patients with cirrhosis.
In the investigator-initiated, randomized, double-blind, placebo-controlled, single-center, phase 2 GALA-RIF trial, the investigators examined adult patients aged 18-75 at the Odense University Hospital. Each participant had current or previous alcohol overuse defined as at least 24 g of alcohol a day for women and at least 36 g per day for men for at least 1 year. The participants also had biopsy-proven alcohol-related liver disease and no previous hepatic decompensation.
Each patient was treated with either oral rifaximin-α 550 mg twice daily (n = 68) or matched placebo (n = 68) for 18 months. The randomization was stratified according to fibrosis stage and alcohol abstinence.
The investigators sought primary endpoints of a histological decrease from baseline to 18 month treatment of at least 1 fibrosis stage, according to the Kleiner fibrosis score. They also assessed the number of patients with progression by at least 1 fibrosis stage from baseline to 18 months.
Overall, 1886 consecutive patients with a history of excessive alcohol consumption and no previous hepatic decompensation were screened between March 23, 2015 and November 10, 2021.
The results show 98% (n = 133) of patients received at least 1 dose of the intervention andwere included in the modified intention-to-treat analysis, of which 79% (n = 108) completed the trial per protocol.
In the per-protocol analysis, 26% (n = 14) of patients in the treatment group had a decrease in fibrosis stage after 18 months, compared to 28% (n = 15) of the placebo group (odds ratio [OR], 1.10; 95% confidence interval [CI]; P = 0.91).
In the per-protocol analysis, there were increases in fibrosis stage for 24% (n = 13) of patients in the rifaximin-α group, compared to 43% (n = 23) of the placebo group (OR, 0.42; 95% CI, 0.18–0.98; P = 0.044).
Finally, the modified intention-to-treat analysis, increases in fibrosis stage occurred in 19% (n = 13) of patients in the treatment group and 35% (n = 23) of the placebo group (OR, 0.45; 95% CI, 0.20-1.02; P = 0.055).
In the safety analysis, the investigators identified 48 (71%) adverse events in the rifaximin-α group, compared to 53 (78%) of the placebo group. They also found 14 (21%) serious adverse events in the treatment group and 12 (18%) in the placebo group, but no serious adverse events were considered related to treatment.
“In patients with alcohol-related liver disease, rifaximin-α might reduce progression of liver fibrosis,” the authors wrote. “These findings warrant confirmation in a multicentre phase 3 trial.”
Israelsen, M., Madsen, B. S., Torp, N., Johansen, S., Hansen, C. D., Detlefsen, S., Andersen, P., Hansen, J. K., Lindvig, K. P., Rasmussen, D. N., Thorhauge, K. H., Kjærgaard, M., Karsdal, M., Hansen, T., Arumugam, M., Trebicka, J., Thiele, M., Krag, A., Anastasiadou, E., … Hansen, T. (2023). Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (gala-rif): A randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Gastroenterology & Hepatology. https://doi.org/10.1016/s2468-1253(23)00010-9