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

This exploratory, randomized, open-label pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic hepatitis B or hepatitis C after viral control. The study included a randomized cohort with advanced liver fibrosis and a non-randomized comparison cohort without advanced fibrosis. Viral control was defined as hepatitis B virus suppression during antiviral therapy or sustained virologic response after hepatitis C treatment. The main questions addressed by the study were: Do participants with advanced liver fibrosis differ from those without advanced fibrosis in their baseline gut microbiota, fecal bile acid profiles, inflammatory markers, or fibrosis-related biomarkers? What within-participant changes in these measures are observed after six months of treatment with ursodeoxycholic acid (UDCA), simvastatin, or combined UDCA plus simvastatin? What descriptive patterns of change are observed across the three active-treatment groups? Advanced liver fibrosis was operationally defined during enrollment as a FibroScan liver stiffness measurement of ≥9.5 kPa. Thirteen participants with presumed advanced liver fibrosis were randomized to observation without study medication, UDCA alone, simvastatin alone, or combined simvastatin plus UDCA. One randomized participant was subsequently excluded from the analysis after eligibility review because the advanced-fibrosis criteria were not confirmed, leaving 12 eligible randomized participants, with three participants in each study group. An additional six participants with non-advanced fibrosis, defined by a FibroScan liver stiffness measurement of \

Inclusion Criteria: * Adults aged 18 to 75 years * Diagnosed with advanced fibrosis; the cohort was operationally defined by a FibroScan liver stiffness measurement of ≥9.5 kPa. * Achieved sustained virological response (SVR) at least 6 months after hepatitis C treatment, or * Non-replicating hepatitis B infection (undetectable viral load) for at least 6 months * Able and willing to provide informed consent Exclusion Criteria: * Current or prior use of statins * Liver decompensation (jaundice, ascites, hepatic coma, or esophagogastric varices) * Diagnosed hepatocellular carcinoma or other liver cancers * Alcoholic liver disease or moderate-to-severe fatty liver * Diagnosed diabetes mellitus * Chronic kidney disease * Use of antibiotics within the past 3 months * Use of gastric ulcer medications such as proton pump inhibitors (PPIs) * Pregnancy or breastfeeding * Any condition deemed by the investigator to interfere with study participation or outcomes