Primary biliary cirrhosis: safety and benefits of established and emerging therapies

Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized histologically by lymphocytic cholangitis and intralobular bile duct destruction. It is a progressive disorder associated with increased mortality and decreased quality of life related to hepatic fibrosis, troublesome symptoms such as fatigue and pruritus, and ultimately endstage cirrhosis. PBC affects adults around the world, and therefore effective treatment of PBC and its associated symptoms constitute significant issues for patients and providers as well as on a public health level. The only approved pharmacotherapy for PBC to date is ursodeoxycholic acid (UDCA), a choleretic, hydrophilic bile acid which has been in clinical use for decades. UDCA is effective in a majority of patients with PBC, but nearly a third of patients are UDCA non-responders. Non-response to UDCA is associated with an increased risk of death or need for liver transplantation (LT). Whereas LT is an effective treatment, it engenders substantial cost and a risk of PBC recurrence, among other complications. Patients who are non-responders to UDCA or have highly symptomatic disease (e.g., intractable pruritus) are thus in critical need of novel therapeutic approaches, which are both safe and effective.

In this review, we provide a synopsis regarding the safety and benefits of established and emerging pharmacotherapies for PBC and present viewpoints on how they may evolve over the next several years.

It is our belief that the pharmacoscope of PBC, as with other cholestatic liver diseases, is likely to see important advancements in the near future.