Clinical Pearls & Morning Reports
Long-term survival remains limited in patients with primary biliary cholangitis who have an incomplete biochemical response to treatment with ursodeoxycholic acid. Corpechot et al. evaluated bezafibrate as adjunctive treatment for primary biliary cholangitis among patients with an inadequate response to ursodeoxycholic acid. Read the latest NEJM Original Article here.
Q: What are some of the features of primary biliary cholangitis?
A: Primary biliary cholangitis is a progressive liver disease of unknown cause that affects primarily women older than 30 years of age. It is characterized by serum autoantibodies, inflammation and destruction of small intrahepatic bile ducts, progressive cholestasis (a distinctive symptom of which is pruritus), and slow progression toward cirrhosis and liver failure.
Q: What is the target of fibrates, including bezafibrate?
A: Fibrates are agonists of peroxisome proliferator–activated receptors (PPAR). Treatment with ursodeoxycholic acid and fibrates has the potential both to improve biochemical measures and to reduce the symptoms of primary biliary cholangitis.
A: In the trial by Corpechot et al., the authors found that among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid, approximately one third of the patients in the bezafibrate group, as compared with no patients in the placebo group, reached the primary outcome (normal levels of the main biochemical markers of the disease at 24 months). Parallel changes with respect to pruritus, fatigue, and noninvasive measures of liver fibrosis were consistent with this result. The trial was not large enough or long enough to assess the effect of bezafibrate on hard outcomes, such as liver transplantation and death. Larger trials will be required to assess the effects on these outcomes.
A: Portal hypertension and a high alkaline phosphatase level at baseline were identified as independent predictors of treatment failure. Advanced cirrhosis and severe cholestasis should therefore be considered as potential limiting factors for adjunctive therapy with bezafibrate. Bezafibrate was associated with a 5% increase in the serum creatinine level. This is a known effect of PPAR-α agonists. Its mechanism may involve renal hemodynamic changes or an increased creatinine release by muscle. As a precaution, bezafibrate use should be evaluated taking kidney function into consideration, especially in patients with diabetes, hypertension, or any known renal disease.