Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines

New guidelines have been produced for the management of primary biliary cholangitis, an infrequent but nonetheless important autoimmune liver disease. We provide a succient commentary and overview of the key features of disease management that arise from these recent guideline recommendations, with a focus on therapy with licensed agents (ursodeoxycholic acid and obeticholic acid) as well as personalised management of disease complications and associated symptoms.

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Obeticholic acid—a new therapy in PBC and NASH

British Medical Bulletin ◽

10.1093/bmb/ldaa006 ◽

2020 ◽

Vol 133 (1) ◽

pp. 95-104 ◽

Cited By ~ 3

Author(s):

Roger W Chapman ◽

Kate D Lynch

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Ursodeoxycholic Acid ◽

Farnesoid X Receptor ◽

Primary Biliary Cholangitis ◽

Second Line ◽

Obeticholic Acid ◽

Second Line Therapy ◽

Line Therapy

Abstract Introduction Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). Sources of data In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC. No medications are currently approved in Europe or the USA for the treatment of NASH. In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. Areas of agreement OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. Areas of controversy The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1–10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH. In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. Growing Points Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. Areas timely for developing research New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.

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British Society of Gastroenterology: diagnosis and management of acute lower gastrointestinal bleeding

Frontline Gastroenterology ◽

10.1136/flgastro-2019-101220 ◽

2019 ◽

Vol 10 (4) ◽

pp. 417-420

Author(s):

Ashley Bond ◽

Philip J Smith

Keyword(s):

Great Britain ◽

Gastrointestinal Bleeding ◽

Collaborative Work ◽

Lower Gastrointestinal Bleeding ◽

British Society ◽

Endoscopic Intervention ◽

National Guidance ◽

Patient Representatives ◽

Key Features ◽

New Guidelines

New guidelines have been produced through collaborative work between the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, National Health Service Blood and Transplants and patient representatives. This is the first UK national guidance for lower gastrointestinal bleeding (LGIB). The focus is the in-hospital management of adult patients presenting with acute LGIB. LGIB refers to patients presenting with bright or dark red blood per rectum, clots per rectum or blood mixed with stool. We provide a commentary and overview of the key features, with a particular focus on risk assessment, management, investigations, and radiological and endoscopic intervention.

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FRI-067-Management of primary biliary cholangitis in the pre-obeticholic acid era, and the rate of non-response to ursodeoxycholic acid (UDCA), in a large real-world cohort of PBC patients in Italy: The CLEO-AIGO database

Journal of Hepatology ◽

10.1016/s0618-8278(19)30817-5 ◽

2019 ◽

Vol 70 (1) ◽

pp. e415 ◽

Cited By ~ 1

Author(s):

Umberto Vespasiani Gentilucci ◽

Floriano Rosina ◽

Luchino Chessa ◽

Valeria Pace Palitti ◽

Antonio Picardi ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Real World ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid

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

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2018-000256 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000256 ◽

Cited By ~ 1

Author(s):

Jennifer Pate ◽

Juilo A Gutierrez ◽

Catherine T Frenette ◽

Aparna Goel ◽

Sonal Kumar ◽

...

Keyword(s):

Liver Disease ◽

Patient Adherence ◽

Treated Patient ◽

Management Strategies ◽

Primary Biliary Cholangitis ◽

Cholestatic Liver Disease ◽

Common Symptom ◽

Obeticholic Acid ◽

Intrahepatic Bile Ducts ◽

Patient Health

Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

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Obeticholic Acid: A New Era in the Treatment of Nonalcoholic Fatty Liver Disease

Pharmaceuticals ◽

10.3390/ph11040104 ◽

2018 ◽

Vol 11 (4) ◽

pp. 104 ◽

Cited By ~ 22

Author(s):

Ludovico Abenavoli ◽

Tetyana Falalyeyeva ◽

Luigi Boccuto ◽

Olena Tsyryuk ◽

Nazarii Kobyliak

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Hepatic Metabolism ◽

Lifestyle Changes ◽

Farnesoid X Receptor ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid ◽

Nonalcoholic Fatty Liver

The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism. NAFLD has been proven to be associated with abnormal FXR activity. Obeticholic acid (OCA) is a first-in-class selective FXR agonist with anticholestatic and hepato-protective properties. Currently, OCA is registered for the treatment of primary biliary cholangitis. However, promising effects of OCA on NASH and its metabolic features have been reported in several studies.

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In Silico Prediction and Pharmacokinetic Comparison of Ursodeoxycholic Acid and Obeticholic Acid in the Management of Primary Biliary Cholangitis

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i2-s.4669 ◽

2021 ◽

Vol 11 (2-S) ◽

pp. 113-117

Author(s):

Manali Sudhir Dhage ◽

Nila Ganamurali ◽

Dhivya Dhanasekaran ◽

Sarvesh Sabarathinam

Keyword(s):

Drug Interactions ◽

Ursodeoxycholic Acid ◽

In Silico ◽

Software Tool ◽

Pharmacokinetic Profile ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid ◽

Acid Therapy ◽

Concurrent Use ◽

Cyp3a4 Enzyme

Background: Primary Biliary Cholangitis (PBC) is a persistent liver disease. Ursodeoxycholic acid is used as a first-line treatment for the past two decades. However, concurrent use of Ursodeoxycholic acid reported with a severe adverse drug reaction. Obeticholic acid has been started utilizing as monotherapy and also with Ursodeoxycholic acid in a patient who is intolerant to Ursodeoxycholic acid therapy. We primarily aimed to compare the pharmacokinetic & toxicity profiles of Ursodeoxycholic acid and Obeticholic acid using in silico methods. Method: The pharmacokinetic profile of UDCA & OCA was observed from PKCSM server online database, OSIRIS® property Explorer, T.E.S.T. (Toxicity estimation software tool) & Molinspiration® is used to estimate the drug toxicity profiles. Result: This computer-aided response provides a great understanding and creates a gap between the theoretical and clinical evidence for UDCA & OCA's preference in PBC management. Conclusion: Co-administration of Obeticholic acid with Ursodeoxycholic acid will be an effective treatment for PBC in patients with UDCA intolerants. However, both medications are well-recognized substrates of the CYP3A4 enzyme and may lead to unintended drug interactions and side effects. Keywords: Primary Biliary Cholangitis, Obeticholic acid, Ursodeoxycholic acid, CYP3A4, Drug Interactions, Pharmacokinetics.

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