Scientists establish the safe dose of statins to use in combination with an antibiotic in the treatment of advanced cirrhosis

A study coordinated by researchers of the Clínic-IDIBAPS and published in The Lancet Gastroenterology & Hepatology establishes the safe dose of simvastatin to be used together with rifaximin, an antibiotic that modulates the intestinal microbiome, in patients with advanced cirrhosis. This article is the result of three years of work of the Liverhope Consortium, a project that is part of the Horizon 2020 European research and innovation framework program and has a budget of 6 million euros.

Dr. Pere Ginès, head of the Hepatology department of the Hospital Clínic and of the group Chronic liver diseases: molecular mechanisms and clinical consequences of IDIBAPS, is the last author of this study and the project coordinator in which a total of 16 institutions participate, between clinical centres, universities and European companies. The first signatory of the study is Dr. Elisa Pose, hepatologist and researcher of the same group of the Clinic-IDIBAPS.

Hepatic cirrhosis, regardless of its origin - hepatitis B or C infection, non-alcoholic fatty liver disease or alcohol consumption - is one of the leading causes of death in Europe. It is responsible for about 170,000 deaths each year and it is estimated that, in the same period of time, it causes one million hospitalizations.

There is no effective treatment to curb the progression of cirrhosis, although in recent years there have been several studies indicating that certain antibiotics and statins have beneficial effects on the disease. Antibiotics, especially rifaximin, modulate the intestinal microbiome and reduce the passage of bacteria and bacterial products into the systemic circulation, an important mechanism of progression of cirrhosis. On the other hand, statins improve circulation within the liver, reduce fibrogenesis and inflammation, both intrahepatic and systemic, and decrease portal hypertension. However, clinical validation of the beneficial effects of this combination therapy has not yet been made.

The LIVERHOPE project aims to evaluate the efficacy of the combination therapy with rifaximin and simvastatin in patients with liver cirrhosis. Researchers have already carried out the first of the two clinical trials planned to test the safety and efficacy of combined treatment with rifaximin and simvastatin. In this first study, published in The Lancet Gastroenterology & Hepatology, they have evaluated two doses of simvastatin, in combination with rifaximin, to determine both the safety and tolerability of the drug in patients with decompensated cirrhosis.

The study involved 44 patients who received one of two tested doses of simvastatin (20 or 40 mg per day), in combination with rifaximin, or placebo. The results that the safe dose of simvastatin to use in combination with the antibiotic is that of 20mg.

"This study has established the basis for the selection of a safe dose of simvastatin to carry out the second clinical trial, the Liverhope Efficacy, which is currently under development. It aims to investigate whether the combination of rifaximin plus simvastatin is useful as a treatment for the prevention of the progression of cirrhosis and development of acute chronic liver failure," says Pere Ginès, who is also full professor of Medicine at the University of Barcelona and CIBEREHD researcher.

The Liverhope project is funded through societal Challenges /Health, demographic change and well-being) of the European Community’s Horizon 2020. (Grant agreement num. 731875).

Article reference:

Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial.
Pose E, Napoleone L, Amin A, Campion D, Jimenez C, Piano S, Roux O, Uschner FE, de Wit K, Zaccherini G, Alessandria C, Angeli P, Bernardi M, Beuers U, Caraceni P, Durand F, Mookerjee RP, Trebicka J, Vargas V, Andrade RJ, Carol M, Pich J, Ferrero J, Domenech G, Llopis M, Torres F, Kamath PS, Abraldes JG, Solà E, Ginès P.
Lancet Gastroenterol Hepatol. 2019 Oct 10. pii: S2468-1253(19)30320-6. doi: 10.1016/S2468-1253(19)30320-6.