Transition from Conventional Drugs to Promising

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by chronic, non-suppurative, destructive cholangitis that eventually leads to cholestasis, fibrosis, cirrhosis and subsequent hepatic failure and death if left untreated. The only available therapeutic agent for PBC is ursodeoxycholic acid (UDCA), which has been demonstrated to delay the development of fibrosis as well as improve patient survival without the need for liver transplantation. However, not all patients achieve a complete biochemical response to UDCA. Fibrate is a fibric acid derivative used in the treatment of hypercholesterolemia and hyperglyceridemia, and it has been incidentally noted to cause a decrease in serum liver biochemical markers. The proposed mechanism of action of fibric acid derivatives involves regulation of the expression of various kinds of lipids and proteins, as well as cell proliferation, through the activation of peroxisome proliferator-activated receptor-α. Obeticholic acid, a first-in-class alternative farnesoid X receptor agonist, is a semi-synthetic bile acid analogue of 6α-ethylchenodeoxycholic acid that is nearly 100-fold more potent than chenodeoxycholic acid. The efficacy of both fibrate and beticholic acid in addition to UDCA in asymptomatic PBC patients who did not respond well to UDCA alone has been confirmed. Further progress in the study of newer drugs that are effective for symptomatic PBC patients is expected in the future.