Novel strategies and therapeutic options for the management of primary biliary cholangitis

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a varied course of progression ranging from being completely asymptomatic to aggressive disease leading to cirrhosis and resulting in liver transplantation. In addition, symptoms can be debilitating and can have a major impact on quality of life. For decades, there was only one anti-cholestatic agent available to target this disease and that was only effective in around half of patients, with little or no effect on symptoms. With increasing understanding of the pathogenic mechanisms of PBC and potential targets for drug treatment, pharmaceutical companies have shown a greater interest in this rare disease. A large number of novel therapeutic molecules have been developed and are currently being evaluated. In this review article all the novel molecules in use and in trials targeting cholestasis and symptoms in PBC are discussed.

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

“…The recommended starting dose for cholestyramine is 4 g per day, with titration up to 16 g per day as needed and tolerated 6. If a patient is prescribed both a bile acid sequestrant and UDCA, these medications should be taken 2–4 hours apart; similarly, because bile acid sequestrants may prevent absorption of OCA, these medications should not be taken within 4 hours of each other 8 36. Additionally, some patients experience issues with cholestyramine tolerability, citing an unpleasant taste and gastrointestinal side effects as reasons for discontinuation 36.…”

“…If a patient is prescribed both a bile acid sequestrant and UDCA, these medications should be taken 2–4 hours apart; similarly, because bile acid sequestrants may prevent absorption of OCA, these medications should not be taken within 4 hours of each other 8 36. Additionally, some patients experience issues with cholestyramine tolerability, citing an unpleasant taste and gastrointestinal side effects as reasons for discontinuation 36. An alternative to cholestyramine use is colestipol, which some patients may find more palatable.…”

“…If bile acid sequestrants are inappropriate for a patient, or if they are insufficient in addressing the symptoms of pruritus, the recommended second-line treatment is rifampicin, a pregnane X receptor agonist. Rifampicin is associated with hepatotoxicity in some patients and should be initiated at a quarter dose and titrated slowly with careful monitoring of liver biochemistries 36. Rifampicin can be given at doses of 150–300 mg twice daily as tolerated; however, rifampicin should not be used in patients with bilirubin levels >2.5 mg/dL 6.…”

“…Rifampicin can be given at doses of 150–300 mg twice daily as tolerated; however, rifampicin should not be used in patients with bilirubin levels >2.5 mg/dL 6. The recommended third-line treatment for pruritus is naltrexone, an opioid antagonist, which should also be initiated at a quarter dose and titrated up based on tolerability 36. Naltrexone should be initiated at a dose of 12.5 mg daily, and uptitrated every 3–7 days to reach the full dose of 50 mg per day 6.…”

“…If these medications are insufficient or not well tolerated, SSRIs, such as sertraline, are a fourth-line option 36. Sertraline has been shown to reduce pruritus symptoms at 75–100 mg doses, which must be achieved through titration 6.…”