Literature Review
Volume 8 Issue 11 - 2021
Emerging Therapies in Primary Biliary Cholangitis (PBC). A Comprehensive Review of the Current Trials
Kleopatra Plessa1, Athanasios Filippou2, Nikolaos Papadopoulos3*, Chara Kani4 and Melanie Deutsch5
1Hellenic Open University, Healthcare Management, Thermi, Greece
2National and Kapodistrian University of Athens, Medical School of Athens, Greece
31st Department of Internal Medicine, 417 Army Share Fund Hospital, Athens, Greece
3University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece
32nd Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National and Kapodistrian University of Athens, Athens, Greece
*Corresponding Author: Nikolaos Papadopoulos, 1st Department of Internal Medicine, 417 Army Share Fund Hospital, Athens, Greece.
Received: October 02, 2021; Published: October 27, 2021




Abstract

Primary biliary cholangitis (PBC) represents a quite rare liver disease. The therapeutic approaches are limited and include the first-line treatment with ursodeoxycholic acid (UDCA). In this review, we summarize and review the emerging therapies for PBC. Ten phase-2 and phase-3 randomized control trials on PBC treatment with 992 subjects have provided data concerning biochemical responses of treatment. 35% of the patients with PBC have an inadequate biochemical response after one year of UDCA. Novel therapies including FXR agonists, PPARs agonists, and Immunomodulators are emerging.

Keywords: Primary Biliary Cholangitis (PBC); Antimitochondrial Antibodies (ΑΜΑ); Ursodeoxy-Cholic Acid (UDCA); Obeticholic Acid (OCA); Peroxisome Proliferator-Activated Receptor (PPAR); Farnesoid X Receptor (FXR)

References

  1. Hirschfield GM., et al. “The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines”. Gut9 (2018): 1568-1594.
  2. Selmi C., et al. “Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis”. Frontiers in Immunology 5 (2014): 128.
  3. Cordell HJ., et al. “International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways”. Nature Communications 6 (2015): 8019.
  4. Kikuchi K., et al. “Genetic polymorphisms of toll-like receptor 9 influence the immune response to CpG and contribute to hyper-IgM in primary biliary cirrhosis”. Journal of Autoimmunity 4 (2005): 347-352.
  5. Bach N and Schaffner F. “Familial primary biliary cirrhosis”. Journal of Hepatology 6 (1994): 698-701.
  6. Selmi C., et al. “Genetics and geoepidemiology of primary biliary cirrhosis: following the footprints to disease etiology”. Seminars in Liver Disease 3 (2005): 265-280.
  7. Kaplan MM and Bianchi DW. “Primary biliary cirrhosis: for want of an X chromosome?” Lancet 9408 (2004): 505-506.
  8. Prince MI and James OFW. “The epidemiology of primary biliary cirrhosis”. Clinics in Liver Disease (2003).
  9. Galoosian A., et al. “Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches”. Journal of Clinical and Translational Hepatology 1 (2020): 49-60.
  10. Cheung K-S., et al. “Epidemiology and Natural History of Primary Biliary Cholangitis in the Chinese: A Territory-Based Study in Hong Kong between 2000 and 2015”. Clinical and Translational Gastroenterology 8 (2017): e116.
  11. Madir A., et al. “Epidemiological and clinical features of primary biliary cholangitis in two Croatian regions: a retrospective study”. Croatian Medical Journal 6 (2019): 494-502.
  12. Lleo A., et al. “Primary biliary cholangitis: a comprehensive overview”. Hepatology International 6 (2017): 485-499.
  13. European Association for the Study of the Liver. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis”. Journal of Hepatology 1 (2017): 145-172.
  14. Lindor KD., et al. “Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases”. Hepatology1 (2019): 394-419.
  15. Kuo A., et al. “Management of symptom complexes in primary biliary cholangitis”. Current Opinion in Gastroenterology 3 (2016): 204-209.
  16. Prince M., et al. “Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years”. Gastroenterology4 (2002): 1044-1051.
  17. Chen S., et al. “A brief review on prognostic models of primary biliary cholangitis”. Hepatology International 5 (2017): 412-418.
  18. Hempfling W., et al. “Ursodeoxycholic acid - adverse effects and drug interactions”. Alimentary Pharmacology and Therapeutics 10 (2003): 963-972.
  19. Purohit T and Cappell MS. “Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy”. World Journal of Hepatology 7 (2015): 926-941.
  20. Aguilar MT and Chascsa DM. “Update on emerging treatment options for primary biliary cholangitis”. Hepatitis Medicine 12 (2020): 69-77.
  21. Nevens F., et al. “A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis”. The New England Journal of Medicine 7 (2016): 631-643.
  22. Trauner M., et al. “Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study”. The Lancet Gastroenterology and Hepatology 6 (2019): 445-453.
  23. Oral abstracts (abstracts 1–288)”. Hepatology1 (2019): 1-187.
  24. Ghonem NS., et al. “Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion”. Hepatology 3 (2014): 1030-1042.
  25. Staels B., et al. “Mechanism of action of fibrates on lipid and lipoprotein metabolism”. Circulation 19 (1998): 2088-2093.
  26. Lefere S., et al. “Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆”. Journal of Hepatology 4 (2020): 757-770.
  27. Corpechot C. “The role of fibrates in primary biliary cholangitis”. Current Hepatology Reports 1 (2019): 107-114.
  28. Schattenberg JM., et al. “A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA”. Journal of Hepatology 6 (2021): 1344-1354.
  29. Da’adoosh B., et al. “Discovering highly selective and diverse PPAR-delta agonists by ligand based machine learning and structural modeling”. Scientific Reports 1 (2019): 1106.
  30. Wedemeyer H., et al. “Final results of a multicenter, open-label phase 2b clinical trial to assess safety and efficacy of Myrcludex B in combination with Tenofovir in patients with chronic …. Journal of …. (2018).
  31. ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA) (2021).
  32. CymaBay Announces Positive Topline Results from ENHANCE for Seladelpar in Patients with Primary Biliary Cholangitis (2021).
  33. Floreani A. “Experimental Pharmacological Agents for the Treatment of Primary Biliary Cholangitis”. Journal of Experimental Pharmacology (2020).
  34. Trivedi HD., et al. “Primary biliary cholangitis: new treatments for an old disease”. Frontline Gastroenterology1 (2017): 29-36.
  35. Angulo P., et al. “Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid”. Hepatology2 (2000): 318-323.
  36. Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants with Primary Biliary Cholangitis (2021).
  37. Genkyotex provides new clinical data from the PBC Phase 2 trial providing further evidence of the anti-fibrotic activity of setanaxib (2021).
Citation: Nikolaos Papadopoulos., et al. “Emerging Therapies in Primary Biliary Cholangitis (PBC). A Comprehensive Review of the Current Trials”. EC Gastroenterology and Digestive System 8.11 (2021): 48-59.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


December Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 20, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.