Resolution of Jaundice in a Patient With Primary Biliary Cholangitis on Obeticholic Acid

Abstract

Primary biliary cholangitis (PBC) is an autoimmune disease marked by destruction of small intralobular bile ducts. Without medical therapy, patients can develop cholestatic liver disease, cirrhosis, and even liver failure. First line therapy with ursodeoxycholic acid (UDCA) is often effective, but up to 35% of patients will experience a suboptimal response. Obeticholic acid (OCA) has been recently approved for use in patients with inadequate response to UDCA alone. In prior trials, the addition of OCA has been associated with significant improvement in alkaline phosphatase (ALP) but only minimal reduction in total bilirubin (Tbil). With this case, we present a patient with inadequate response to UDCA who demonstrated remarkable improvement with marked reduction in ALP and resolution of jaundice after the addition of OCA. A 62 year old female presented with jaundice and labs revealed elevated liver-associated enzymes (LAEs), notably ALP 912 and Tbil 3.9. PBC was diagnosed based on positive AMA and liver biopsy findings. Histology also noted stage 3 hepatic fibrosis. She was started on UDCA 500mg twice daily with initial improvement in ALP but not Tbil (Figure 1). MRCP revealed a questionable focal biliary stricture, although endoscopic stenting did not lead to biochemical improvement and no stricture was seen on subsequent imaging. Repeat liver biopsy confirmed PBC and excluded overlap of autoimmune hepatitis. Due to persistent jaundice, the patient was started on OCA 5mg daily in conjunction to her UDCA. After six months, ALP has slowly declined to 279, and other LAEs have normalized with Tbil 0.8. OCA is a novel agent farnesoid X receptor agonist and has direct anti-cholestatic and anti-fibrotic effects. The addition of OCA to UDCA is associated with a 20-25% reduction in ALP. While our patient had an expected decline in ALP, the more remarkable finding has been the complete resolution of her hyperbilirubinemia with the combination of UDCA and low dose OCA. Her Mayo risk score declined from intermediate to low risk of death (7.8 to 5.7). This unexpected clinical improvement has allowed us to continue medical management while deferring liver transplant evaluation. More long-term data are needed to determine whether OCA impacts overall and transplant-free survival in patients with PBC.