Bezafibrate, PBC and Transplant-free survival

Bezafibrate has emerged as a significant therapeutic agent for improving transplant-free survival in patients with primary biliary cholangitis (PBC) when used in combination with ursodeoxycholic acid (UDCA). PBC is a chronic autoimmune liver disease that can progress to cirrhosis and liver failure, necessitating liver transplantation. While UDCA remains the first-line treatment, a subset of patients exhibits incomplete biochemical responses, requiring additional therapeutic interventions.

Recent real-world evidence from a large Japanese cohort study, encompassing 3,908 patients and over 21,000 patient-years, demonstrated that the combination of bezafibrate (BZF) and UDCA substantially improved long-term outcomes. Patients receiving UDCA + BZF experienced a marked reduction in the risk of all-cause mortality and liver-related death or transplantation, with adjusted hazard ratios of 0.33 and 0.27, respectively, both highly significant (p < 0.001). This survival benefit was consistent across various baseline risk groups, underscoring the robustness of the findings.

The clinical benefit of the combination therapy was quantified through the number needed to treat (NNT). To prevent one additional death or liver transplantation, the NNT was 29 at 5 years, 14 at 10 years, and 8 at 15 years, highlighting its substantial long-term efficacy. Importantly, bezafibrate not only improves biochemical markers and symptoms, as shown in prior trials, but also enhances survival outcomes, reinforcing its role as a second-line treatment for PBC.

These findings strongly support the routine use of bezafibrate alongside UDCA in patients with incomplete response, offering a promising strategy to improve transplant-free survival and overall disease management in PBC.