Old and new treatments for primary biliary cholangitis

Abstract

Primary biliary cholangitis (formerly primary biliary cirrhosis) is a rare progressive cholestatic liver disease, whose hallmark features include a persistently elevated alkaline phosphatase level, presence of anti-mitochondrial antibodies and characteristic histology. Since 1998, ursodeoxycholic acid (UDCA), a bile acid, has been the only available therapeutic agent. Primary biliary cholangitis is associated with the development of end-stage liver disease, increased morbidity and mortality. UDCA has been shown to improve serum biochemistries, histology and delay the need for liver transplantation. The clinical issue is that approximately 25%-40% of patients do not respond to this standard therapy. In recent years, many trials have investigated alternative and adjunctive treatments, leading to the recent approval of obeticholic acid, an analogue of chenodeoxycholic acid, which has shown significant and sustained reductions in alkaline phosphatase levels in combination with UDCA. Obeticholic acid has rapidly been embraced as a new agent to improve the biochemical profile in refractory patients, in addition to being approved for use as monotherapy in patients who cannot tolerate UDCA. There are several other studies and targets which are being investigated. This review is intended to highlight the benefits of UDCA, educate the reader on the newly available obeticholic acid, and to summarize the many ongoing trials and therapeutic targets being investigated in attempts to control and cure primary biliary cholangitis.

Treatment of PBC—A step forward

“…In the current issue of Liver International, Chascsa et al 1 reviewed therapies in primary biliary cholangitis (PBC), a rare autoimmune and cholestatic liver disease. They reported on data efficacy of ursodeoxycholic acid (UDCA), results from phase II and III trials, which has led to the registration of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) in PBC, and summarized the novel molecules currently in different phases of development.…”

“…In the current issue of Liver International, Chascsa et al . reviewed therapies in primary biliary cholangitis (PBC), a rare autoimmune and cholestatic liver disease.…”

Evaluation of the United Kingdom‐primary biliary cholangitis and global primary biliary cholangitis group prognostic models for primary biliary cholangitis patients treated with ursodeoxycholic acid in the U.S. population

“…Use of the aforementioned advanced prognostic models in patients with PBC has become a standard method to manage, monitor, and risk stratify UDCA users . The advancements of liver transplant and the development of alternative effective therapies for UDCA nonresponders have led to the wider use of those biomarkers . For example, the application of those prognostic biomarkers allows for appropriate candidate selection of second‐line therapies and aids in identifying high‐risk patients for a closer follow‐up or the consideration of liver transplant.…”

Finding the cure for primary biliary cholangitis – Still waiting

“…Until relatively recently, there has not been a single new therapy introduced in primary biliary cholangitis (PBC) for nearly 20 years despite intensive efforts and remarkable discoveries in human and murine models of PBC and in liver immunology . In this current issue, we were delighted to read the paper entitled “Old and New Treatments for Primary biliary Cholangitis” . In this article, the authors have carefully described the therapies used in PBC.…”

“…[1][2][3][4][5][6][7][8][9] In this current issue, we were delighted to read the paper entitled "Old and New Treatments for Primary biliary Cholangitis". 10 In this article, the authors have carefully described the therapies used in PBC. It is emphasized that before the era of ursodeoxycholic acid (UDCA), patients with PBC were all too often untreated and often progressed to cirrhosis.…”