Early intervention in PBC

Diagnosing primary biliary cholangitis (PBC) and initiating ursodeoxycholic acid (UDCA) as early as possible may delay histological progression1,2

UDCA THERAPY

Without therapeutic intervention, a subset of patients with PBC can progress from one histological stage to the next as rapidly as every 2 years.3

  • UDCA is the current standard of care in PBC therapy
    • It acts by dilution and alkalinization of the bile acid pool, resulting in reduced cholestasis4-6
  • UDCA lowers alkaline phosphatase (ALP) in patients with PBC who respond biochemically7
  • Randomized studies demonstrate that UDCA improves biochemical cholestasis5,8,9
  • In randomized studies, serum concentrations of bilirubin, an important prognostic marker, were reduced by UDCA5,8,9
  • In an early study, the rate of histological progression to cirrhosis was significantly lower in the UDCA group than in the control group (13% vs 49%; P=.009)10
  • UDCA therapy was associated with a 5-fold lower rate of progression from early-stage disease to extensive fibrosis or cirrhosis11
  • Disease progression took place at a rate of 7% per year in patients treated with UDCA vs 34% per year in patients taking placebo (P<.002)11
  • At 4 years the probability of remaining in early-stage disease was 76% in patients treated with UDCA11

References:  1. Shi J, Wu C, Lin Y, Chen Y-X, Zhu L, Xie W-F. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101(7):1529-1538. doi:10.1111/j.1572-0241.2006.00634.x.  2. Al-Harthy N, Kumagi N. Natural history and management of primary biliary cirrhosis. Hepat Med. 2012;4:61-71. doi:10.2147/HMER.S25998.  3. Locke GR III, Therneau TM, Ludwig J, Dickson ER, Lindor KD. Time course of histological progression in primary biliary cirrhosis. Hepatology. 1996;23(1):52-56. doi:10.1053/jhep.1996.v23.pm0008550048.  4. Crosignani A, Podda M, Battezzati PM, et al. Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration. Hepatology. 1991;14(6):1000-1007. doi:10.1002/hep.1840140609.  5. Poupon R. Primary biliary cirrhosis: a 2010 update. J Hepatol. 2010;52(5):745-758. doi:10.1016/j.jhep.2009.11.027.  6. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525-531. doi:10.1053/jhep.2002.36088.  7. Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008;48(3):871-877. doi:10.1002/hep.22428.  8. Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian multicenter double-blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994;19(5):1149-1156. doi:10.1002/hep.1840190512.  9. Combes B, Carithers RL Jr, Maddrey WC, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1995;22(3):759-766. doi:10.1002/hep.1840220311.  10. Angulo P, Batts KP, Therneau TM, Jorgensen RA, Dickson ER, Lindor KD. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis. Hepatology. 1999;29(3):644-647. doi:10.1002/hep.510290301.  11. Corpechot C, Carrat F, Bonnand A-M, Poupon RE, Poupon R. The effect of ursodeoxycholic acid on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000;32(6):1196-1199. doi:10.1053/jhep.2000.20240.