Expert opinion on pharmacotherapy · 2014
Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis.
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Silveira Marina G, Lindor Keith D
Аннотация
INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of adults. Treatments are needed when patients have incomplete response to ursodeoxycholic acid (UDCA).
AREAS COVERED: Discoveries of the key role played by bile acids (BAs) and nuclear receptors (NRs) in regulating liver and metabolic homeostasis have led to promising therapeutic approaches in liver diseases. A PubMed search for the recent literature on NRs in liver disease was conducted. In particular, obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist that has an important role in the enterohepatic circulation of BAs. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone. Pruritus is the most common side effect, limiting treatment at higher doses. Budesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist also involved in BA synthesis, metabolism and transport. Studies with budesonide have shown positive effects of short-term combination therapy in selected patients with early stage disease and overlapping features of autoimmune hepatitis.
EXPERT OPINION: Though larger studies are needed, preliminary results of agents targeting FXR and PXR have been encouraging, particularly in subsets of patients with PBC and may mark a new therapeutic era.
AREAS COVERED: Discoveries of the key role played by bile acids (BAs) and nuclear receptors (NRs) in regulating liver and metabolic homeostasis have led to promising therapeutic approaches in liver diseases. A PubMed search for the recent literature on NRs in liver disease was conducted. In particular, obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist that has an important role in the enterohepatic circulation of BAs. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone. Pruritus is the most common side effect, limiting treatment at higher doses. Budesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist also involved in BA synthesis, metabolism and transport. Studies with budesonide have shown positive effects of short-term combination therapy in selected patients with early stage disease and overlapping features of autoimmune hepatitis.
EXPERT OPINION: Though larger studies are needed, preliminary results of agents targeting FXR and PXR have been encouraging, particularly in subsets of patients with PBC and may mark a new therapeutic era.