The CIBEREHD group from the Digestive Diseases Department at Hospital de Sant Pau has participated in an international clinical trial recently published in JAMA (Journal of the American Medical Association), one of the most prestigious medical journals worldwide. The study, conducted within the framework of the LIVERHOPE Consortium and led by Dr. Elisa Pose and Dr. Pere Ginès from Hospital Clínic de Barcelona, evaluated whether the combined administration of simvastatin and rifaximin, added to standard treatment, could reduce clinical complications and mortality in patients with decompensated cirrhosis—one of the most severe and complex stages of liver disease. The study was funded through a Horizon 2020 grant with European funds.
The study was conducted between January 2019 and December 2022 and included a total of 237 patients with decompensated cirrhosis recruited from 14 European centers, including Hospital de Sant Pau. It was a double-blind, randomized, placebo-controlled trial in which participants received either the combination of simvastatin (20 mg/day) and rifaximin (1,200 mg/day) or a placebo for one year, in addition to standard medical therapy.
The scientific rationale behind this combination lies in their complementary mechanisms of action. Simvastatin not only lowers blood cholesterol levels but is also known for its anti-inflammatory and antifibrotic properties, as well as its ability to reduce hepatic portal pressure—effects that, in a previous clinical study, appeared to reduce mortality. Rifaximin, on the other hand, is an antibiotic with very low systemic absorption that modulates the gut microbiome and likely inhibits bacterial translocation, endotoxemia, and inflammation, helping to reduce hepatic encephalopathy. Based on this, the project set out to determine whether this combined strategy could prevent the development of the severe condition known as acute-on-chronic liver failure (ACLF), other cirrhosis-related complications, and mortality.
However, the results were unexpected. The study showed no significant differences between the treated group and the placebo group in terms of ACLF incidence, liver transplant rates, or mortality. There were also no differences in the occurrence of typical cirrhosis complications such as ascites, hepatic encephalopathy, esophageal variceal bleeding, acute kidney injury, or infections.
As for safety, the therapeutic combination was generally well tolerated, although a few cases of rhabdomyolysis—a muscle-related complication—were reported in the treatment group. This underscores the need for caution when using statins in this patient population. This trial was based on previous phase II studies that had shown a good safety profile with low doses of simvastatin, like those used in the current study, although higher doses had occasionally been linked to liver and muscle toxicity.
Although the results were not positive, the researchers emphasized the importance of publishing this kind of evidence. In the words of Dr. Germán Soriano, physician in the Digestive Diseases Department at Hospital de Sant Pau and one of the authors of the article, “This study is a clear example that in clinical research, negative results are also valuable. They help us rule out approaches that seemed promising and better focus our efforts on strategies that are truly effective for our patients.” Dr. Soriano also highlighted the significance of participating in a multicenter study of this caliber: “It is important for Sant Pau to be part of international alliances that allow us to tackle global clinical challenges with a collaborative and rigorous approach.”
Reference article:
Pose E, Jiménez C, Zaccherini G, Campion D, Piano S, Uschner FE, de Wit K, Roux O, Gananandan K, Laleman W, Solé C, Alonso S, Cuyàs B, Ariza X, Juanola A, Ma AT, Napoleone L, Gratacós-Ginès J, Tonon M, Pompili E, Sánchez-Delgado J, Allegretti AS, Morales-Ruiz M, Carol M, Pérez-Guasch M, Fabrellas N, Pich J, Martell C, Joyera M, Domenech G, Ríos J, Torres F, Serra-Burriel M, Hernáez R, Solà E, Graupera I, Watson H, Soriano G, Bañares R, Mookerjee RP, Francoz C, Beuers U, Trebicka J, Angeli P, Alessandria C, Caraceni P, Vargas VM, Abraldes JG, Kamath PS, Ginès P, LIVERHOPE Consortium. Simvastatin and rifaximin in decompensated cirrhosis: A randomized clinical trial. JAMA 2025;333:864–74. https://doi.org/10.1001/jama.2024.27441
