Remedial Mechanism of Simvastatin and Ursodeoxycholic Acid in Liver Cirrhosis: Crosstalk of Bile Secretion, Gut Microbiome, and Host Immune Response

Summary

The goal of this clinical trial is to learn whether simvastatin alone or in combination with ursodeoxycholic acid (UDCA) can reduce liver fibrosis, inflammation, and gut microbiota imbalance in patients with liver cirrhosis who have achieved viral eradication after hepatitis C or inactive hepatitis B. The main questions the study aims to answer are: Can simvastatin or UDCA reduce biomarkers of liver fibrosis and chronic inflammation? Do these treatments improve gut microbiota composition and bile acid metabolism? Is combination therapy more effective than either drug alone? In this study, 120 patients with stable liver cirrhosis will be randomly assigned to one of four groups: no treatment (control), UDCA alone, simvastatin alone, or simvastatin plus UDCA. Patients will be followed for 6 months, during which stool, blood, and skin samples will be collected to assess gut microbiota, bile acid profiles, inflammatory markers, and fibrosis indicators. A group of 30 healthy individuals without cirrhosis will also provide baseline comparisons for microbiota and bile acid profiles.

Timeline

Start

2025-09-01

Primary completion

2025-12-31

Completion

2025-12-31

Publications

• Results Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, Ogura Y, Hayashi T, Yokota A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81. doi: 10.1053/j.gastro.2011.07.046. Epub 2011 Aug 10.
• Results Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011 Aug;54(2):562-72. doi: 10.1002/hep.24423. Epub 2011 Jun 26.
• Results Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15;303(6):G675-85. doi: 10.1152/ajpgi.00152.2012. Epub 2012 Jul 19.
• Results Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. doi: 10.1152/ajpgi.00190.2011. Epub 2011 Sep 22.

Drugs

Indications