The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

2019 ◽  
Vol 40 (01) ◽  
pp. 034-048 ◽  
Author(s):  
Ana Lleo ◽  
Patrick S.C. Leung ◽  
Gideon M. Hirschfield ◽  
Eric M. Gershwin
Keyword(s):  
Active Role ◽  
Medium Size ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Key Factors ◽  
Intrahepatic Bile Ducts ◽  
Autoimmune Destruction ◽  
Chronic Cholestasis ◽  
Immune Mediated ◽  
Mitochondrial Antigens

AbstractPrimary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.

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

2019 ◽  
Vol 6 (1) ◽  
pp. e000256 ◽  
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.

Primary biliary cirrhosis

2010 ◽  
pp. 2464-2468
Author(s):  
M.F. Bassendine ◽  
D.E.J. Jones
Keyword(s):  
Liver Disease ◽  
Epithelial Cells ◽  
Primary Biliary Cirrhosis ◽  
Case History ◽  
Bile Ducts ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Blood Tests ◽  
Intrahepatic Bile Ducts ◽  
Immune Mediated

Case History—A 60 yr old woman presenting with abnormal liver blood tests. Primary biliary cirrhosis is a chronic, cholestatic liver disease in which the biliary epithelial cells lining the small intrahepatic bile ducts are the target for immune-mediated damage leading to progressive ductopenia. The cause is unknown, but presumed to be autoimmune....

scholarly journals rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuki Hitomi ◽  
Yoshihiro Aiba ◽  
Yosuke Kawai ◽  
Kaname Kojima ◽  
Kazuko Ueno ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Autoimmune Reaction ◽  
Expression Levels ◽  
Intrahepatic Bile Ducts ◽  
Genome Wide ◽  
Functional Analyses

AbstractPrimary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome-wide association study (GWAS) identified chromosome 11q23.1 as a susceptibility gene locus for PBC in the Japanese population. Here, high-density association mapping based on single nucleotide polymorphism (SNP) imputation and in silico/in vitro functional analyses identified rs1944919 as the primary functional variant. Expression-quantitative trait loci analyses showed that the PBC susceptibility allele of rs1944919 was significantly associated with increased COLCA1/COLCA2 expression levels. Additionally, the effects of rs1944919 on COLCA1/COLCA2 expression levels were confirmed using genotype knock-in versions of cell lines constructed using the CRISPR/Cas9 system and differed between rs1944919-G/G clones and -T/T clones. To our knowledge, this is the first study to demonstrate the contribution of COLCA1/COLCA2 to PBC susceptibility.

scholarly journals Mesenchymal Stem Cells as New Therapeutic Agents for the Treatment of Primary Biliary Cholangitis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Aleksandar Arsenijevic ◽  
C. Randall Harrell ◽  
Crissy Fellabaum ◽  
Vladislav Volarevic
Keyword(s):  
Therapeutic Potential ◽  
Alternative Therapy ◽  
Therapeutic Agents ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Cellular Mechanisms ◽  
Safety Issues ◽  
Intrahepatic Bile Ducts ◽  
The Us ◽  
End Stage

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by the progressive destruction of small- and medium-sized intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. Ursodeoxycholic acid and obethicholic acid are the only agents approved by the US Food and Drug Administration (FDA) for the treatment of PBC. However, for patients with advanced, end-stage PBC, liver transplantation is still the most effective treatment. Accordingly, the alternative approaches, such as mesenchymal stem cell (MSC) transplantation, have been suggested as an effective alternative therapy for these patients. Due to their immunomodulatory characteristics, MSCs are considered as promising therapeutic agents for the therapy of autoimmune liver diseases, including PBC. In this review, we have summarized the therapeutic potential of MSCs for the treatment of these diseases, emphasizing molecular and cellular mechanisms responsible for MSC-based effects in an animal model of PBC and therapeutic potential observed in recently conducted clinical trials. We have also presented several outstanding problems including safety issues regarding unwanted differentiation of transplanted MSCs which limit their therapeutic use. Efficient and safe MSC-based therapy for PBC remains a challenging issue that requires continuous cooperation between clinicians, researchers, and patients.

scholarly journals Genetic association of E26 transformation specific sequence 1 polymorphisms with the susceptibility of primary biliary cholangitis in China

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Huan Xu ◽  
Qian Niu ◽  
Zhenzhen Su ◽  
Fang Wang ◽  
Junlong Zhang ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Specific Sequence ◽  
Low Level ◽  
Intrahepatic Bile Ducts ◽  
Homozygous Genotype ◽  
High Level

AbstractPrimary biliary cholangitis (PBC) is a chronic and cholestatic liver disease characterized by an autoimmune-mediated destruction of intrahepatic bile ducts. E26 transformation specific sequence 1 (ETS-1) is a transcription factor regulating the expression of various immune-related genes. The aim of our study was to identify the associations between the gene polymorphisms of ETS-1 with the susceptibility and clinical characteristics of PBC in Chinese Han population. Three single nucleotide polymorphisms (rs4937333, rs11221332 and rs73013527) of ETS-1 were selected based on relevant studies. Genotyping was executed with polymerase chain reaction-high resolution melting (PCR-HRM) assay. SNP rs4937333 of ETS-1 was prominent correlation with the susceptibility of PBC (P = 0.007, OR = 1.44, 95%CI = 1.10–1.88). For rs4937333, PBC patients carrying the allele T assumed high-level TP (P = 0.020), and homozygous genotype TT assumed low-level RDW (P = 0.033). For rs11221332, PBC patients carrying the allele T assumed high-level TP and HDLC (P = 0.004, P = 0.015, respectively). For rs73013527, PBC patients carrying the allele T assumed low-level PLT (P = 0.002), and homozygous genotype TT assumed high-level RDW (P = 0.021). In conclusion, Gene polymorphisms of ETS-1 present relevant with the susceptibility of PBC, and affect the expression of TP, HDLC, PLT and RDW concentrations in patients with PBC.

scholarly journals Widespread gaps in the quality of care for primary biliary cholangitis in UK

2021 ◽  
pp. flgastro-2020-101713
Author(s):  
Mathuri Sivakumar ◽  
Akash Gandhi ◽  
Eathar Shakweh ◽  
Yu Meng Li ◽  
Niloufar Safinia ◽  
...  
Keyword(s):  
Quality Of Care ◽  
Medical Records ◽  
Clinical Symptoms ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Patient Demographics ◽  
Risk Patients ◽  
Wide Scale ◽  
The Uk

ObjectivePrimary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines.DesignData were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ2 analysis for variation in performance between trusts.Results790 patients’ medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297).ConclusionOur findings identify a broad-based deficiency in ‘real-world’ PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.

scholarly journals Portrait of the ‘Absent’ Father: The Impact of Non-Residency on Developing and Maintaining a Fathering Role

2005 ◽  
Vol 14 (2) ◽  
pp. 134-154 ◽  
Author(s):  
Mary P. Corcoran
Keyword(s):  
Exploratory Study ◽  
Active Role ◽  
Absent Father ◽  
Key Factors ◽  
Social Barriers ◽  
Institutional Economic ◽  
Key Issues ◽  
The Impact

This paper reports on an exploratory study conducted with non-resident fathers, to elucidate the key issues affecting the development and maintenance of a fathering role after a relationship has ended. In particular, the paper focuses on the contingent nature of fatherhood for young marginalised men in Dublin. The extent to which fathers identify with a fathering role is explored and comparisons are drawn between the experiences of estranged, committed and activist fathers. Key factors that militate against fathers maintaining an active role in their children's lives are identified. The paper concludes that while the experiences of fatherhood vary across different categories of fathers, the majority of them aspire toward and value their fathering role. However, their capacity to adopt a positive fathering role is affected by a range of institutional, economic and social barriers.

Cholestatic Liver Injury: Care of Patients With Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

2016 ◽  
Vol 27 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Laurie Larson ◽  
Michelle James ◽  
Andrea Gossard
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Outpatient Setting ◽  
Primary Biliary Cholangitis ◽  
Malignant Neoplasms ◽  
Cholestatic Liver Disease ◽  
Gallbladder Polyps ◽  
Increased Risk ◽  
Common Causes

The most common causes of chronic cholestatic liver disease are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both disease processes are characterized by a destruction of intrahepatic and/or extrahepatic biliary ducts. The etiology is not entirely clear; however, there is an underlying autoimmune component contributing to both disease processes. Although PBC and PSC are often diagnosed and managed in the outpatient setting, in some instances, a patient may have jaundice, fatigue, and pruritus requiring evaluation and determination of the cholestatic cause. Patients with PSC should be monitored for evidence of cholangiocarcinoma, colon cancer, and gallbladder polyps as they are at an increased risk of malignant neoplasms. Liver transplant has the potential for improving quality of life, although disease recurrence is a risk.

Drug-Induced Vanishing Bile Duct Syndrome: From Pathogenesis to Diagnosis and Therapeutics

2021 ◽  
Author(s):  
Fernando Bessone ◽  
Nidia Hernández ◽  
Mario Tanno ◽  
Marcelo G. Roma
Keyword(s):  
Bile Duct ◽  
Diagnostic Tools ◽  
Drug Induced ◽  
Vanishing Bile Duct Syndrome ◽  
Beneficial Effects ◽  
Intrahepatic Bile Ducts ◽  
Chronic Cholestasis ◽  
Vanishing Bile Duct ◽  
Therapeutic Alternatives ◽  
Duct Syndrome

AbstractThe most concerned issue in the context of drug/herb-induced chronic cholestasis is vanishing bile duct syndrome. The progressive destruction of intrahepatic bile ducts leading to ductopenia is usually not dose dependent, and has a delayed onset that should be suspected when abnormal serum cholestasis enzyme levels persist despite drug withdrawal. Immune-mediated cholangiocyte injury, direct cholangiocyte damage by drugs or their metabolites once in bile, and sustained exposure to toxic bile salts when biliary epithelium protective defenses are impaired are the main mechanisms of cholangiolar damage. Current therapeutic alternatives are scarce and have not shown consistent beneficial effects so far. This review will summarize the current literature on the main diagnostic tools of ductopenia and its histological features, and the differential diagnostic with other ductopenic diseases. In addition, pathomechanisms will be addressed, as well as the connection between them and the supportive and curative strategies for ductopenia management.

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