PBC is characterized by inflammation and T cell–mediated destruction of intrahepatic bile ducts1-3
1
Immune-mediated damage to cells
in the bile ducts leads to inflammation and bile duct destruction1
2
Bile acids leak out of damaged ducts into the liver parenchyma1
3
Bile acid buildup in the liver leads
to cholestasis4


Chronic cholestasis can lead to fibrosis and development of cirrhosis3,4
Up to 50% of patients on UDCA do not adequately respond to treatment5
Insufficient biochemical response can predict the risk of disease progression6
Expert consensus for PBC treatment guidelines include:

Monitoring liver lab tests every 3-6 months with evaluation of UDCA response at 6-12 months7,8

Pursuing ALP normalization8,9
Treatment goals are shifting to a more individualized approach, aiming to normalize ALP and prioritize quality of life9
Inadequate 12-month response to UDCA can be predicted at
6 months6
According to predictive modeling based on a Global PBC Study Group analysis, an ALP threshold of 1.9 x ULN at 6 months predicts both UDCA treatment response and long-term outcomes6

This threshold is associated with a 90% negative predictive value of UDCA response, or only 10% risk of overtreating6

Transplant-free survival was higher among patients with ALP ≤1.9 x ULN at 6 months compared with ALP >1.9 x ULN at 6 months6
ALP=alkaline phosphatase; PBC=primary biliary cholangitis; ULN=upper limit of normal; UDCA=ursodeoxycholic acid.
References: 1. Younossi ZM, Bernstein D, Shiffman ML, et al. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol. 2019;114(1):48-63. 2. Schnabl B. PPAR agonists in primary biliary cholangitis. N Engl J Med. 2024;390(9):855-858. 3. Carbone C, Milani C, Gerussi A, et al. Primary biliary cholangitis: a multifaceted pathogenesis with potential therapeutic targets. J Hepatol. 2020;73(4):965-966. 4. Galoosian A, Hanlon C, Zhang J, et al. Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches. J Clin Transl Hepatol. 2020;8(1):49-60. 5. Hirschfield GM, Chazouillères O, Cortez-Pinto H, et al. A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients. Expert Rev Gastroenterol Hepatol. 2021;15(8):929-939. 6. Murillo Perez CF, Ioannou S, Hassanally I, et al; Global PBC Study Group. Optimizing therapy in primary biliary cholangitis: alkaline phosphatase at six months identifies one-year non-responders and predicts survival. Liver Int. 2023;43(7):1497-1506. 7. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. 8. Kowdley KV, Bowlus CL, Levy C, et al. Application of the latest advances in evidence-based medicine in primary biliary cholangitis. Am J Gastroenterol. 2023;118(2):232-242. 9. Levy C, Manns M, Hirschfield G. New treatment paradigms in primary biliary cholangitis. Clin Gastroenterol Hepatol. 2023;21(8):2076-2087.