Table 1.
Medical Therapy for Primary Biliary Cholangitis.
| Agent | Rationale | Seminal/current study results and evaluations | Side effects |
|---|---|---|---|
| UDCA | • Increases polarized BA pool • Upregulates BA exchangers in biliary epithelium • Oxygen radical scavenger • Immunomodulator |
• Improves liver biochemistries • Delays histological progression • Improves transplant-free survival • Prevents recurrence after LTx |
• Change in bowel habits • Occasional headaches, dizziness |
| OCA | • Activates FXR • Hepatocytes: increased expression of BA export pumps • Enterocytes: Decreases enterohepatic BA absorption & circulation • Increases expression of FGF-19 ○ Hepatocytes: decreases BA synthesis ○ Enterocytes: decrease BA enterohepatic circulation |
• Improves liver biochemistries • POISE Trial (NCT01473524, Phase III)—effects on liver biochemistries • COBALT Trial (NCT0230811)—outcomes including LTx and death |
• Pruritus |
| Fibrates | • Decreases expression of inflammatory cytokines • Activates PPARα ○ Hepatocytes: decreases BA synthesis & BA export from bile canalicular epithelium |
• Improves liver biochemistries • No survival benefits currently identified • BEZURSO Trial (NCT01654731, Phase III): primary aim- effects on liver enzymes; secondary aim- transplant-free survival |
• Muscle pain, myositis • Pruritus • Heartburn • Elevated transaminases |
| Budesonide | • Anti-inflammatory through nuclear glucocorticoid receptors | • Improves liver biochemistries • Possibly improves liver histology and delays progression • NCT00746486—effects on treatment response |
• Decreased immunity • Decreased bone density • Adrenal suppression • Cutaneous changes • Hirsutism • Hyperglycemia Weight gain |
| Biologics | • Specific monoclonal antibodies to antigens in the humoral immune response | • Rituximab—minimal effect on liver biochemistries • Ustekinumab—no effect on liver biochemistries |
• Decreased immunity • Neuropathy |
Abbreviations: BA: bile acid; LTx: liver transplantation; FXR: farnesoid X receptor; FGF-19: fibroblast growth factor-19; PPARα: proliferator-activated α-receptor.