FXR agonist in post-liver transplantation patients: a randomized open-labeled study. [Protocol]

<ns7:p>Abstract Liver diseases cause nearly 2 million deaths worldwide each year, with approximately 1 million deaths from cirrhosis complications and another 1 million from viral hepatitis and liver cancer, according to WHO estimates. Liver transplantation (LT) remains the primary curative option, boasting success rates of 85% in the first year and 75% at five years post-transplant. Despite high costs, LT is considered cost-effective, especially for younger patients with active work years remaining. However, post-transplant complications, particularly intrahepatic cholestasis, present notable challenges. This complication arises from factors such as ischemia-reperfusion injury, infections, immunological rejection, and surgical complications, all contributing to impaired bile flow and liver damage. Current medical therapies for post-LT cholestasis are limited, with ursodeoxycholic acid (UDCA) frequently used, despite questionable efficacy. Obeticholic acid (OCA), a potent Farnesoid X Receptor (FXR) agonist approved by the FDA for treating primary biliary cholangitis (PBC), has shown potential benefits in reducing elevated cholestatic liver enzymes. Given its significant effects on liver health, OCA may offer therapeutic value in managing post-transplant cholestasis and improving graft survival. This randomized controlled trial (RCT) aims to evaluate OCA’s efficacy compared to UDCA in reducing cholestatic injury and enhancing graft function post-LT. The primary outcomes will focus on a 15% reduction in alkaline phosphatase and gamma-glutamyl transferase levels at 3, 6, and 12 months from baseline one month. Secondary outcomes include molecular markers, biliary complications, graft rejection, quality of life, and cost-effectiveness. Results are anticipated to demonstrate that OCA could ameliorate cholestasis, improve graft survival, reduce post-transplant complications, and enhance quality of life, potentially setting a new standard in post-LT care if found beneficial.</ns7:p>