Primary biliary cholangitis: a multifaceted pathogenesis with potential therapeutic targets

Carbone, Marco; Milani, Chiara; Gerussi, Alessio; Ronca, Vincenzo; Cristoferi, Laura; Invernizzi, Pietro

doi:10.1016/j.jhep.2020.05.041

Cited by 19 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunosuppression in AIH and PBC can be beneficial, however this is not the case for PSC (25). Current therapies are not curative and vary in efficacy in a manner that is presently challenging to predict for each patient, stressing the need for new treatments that effectively dampen inflammation in the liver to prevent the need for a transplant (26)(27)(28)(29). Treg cell therapies are in various stages of development for AIH but not for cholangiopathies (25,27).…”

Section: Targeting Enclysis In Autoimmune Liver Diseasementioning

confidence: 99%

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

et al. 2021

View full text Add to dashboard Cite

Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed. Harnessing the power of the immune system has shown promise in certain autoimmunity and cancer settings. In the context of the liver, regulatory T cell (Treg) therapies are in development. The hypothesis is that these specialized lymphocytes that dampen inflammation may reduce liver injury in patients with chronic, progressive diseases, and promote transplant tolerance. Various strategies including intrinsic and extracorporeal expansion of Treg cells, aim to increase their abundance to suppress immune responses. We recently discovered that hepatocytes engulf and delete Treg cells by enclysis. Herein, we propose that inhibition of enclysis may potentiate existing regulatory T cell therapeutic approaches in patients with autoimmune liver diseases and in patients receiving a transplant. Moreover, in settings where the abundance of Treg cells could hinder beneficial immunity, such us in chronic viral infection or liver cancer, enhancement of enclysis could result in transient, localized reduction of Treg cell numbers and tip the balance towards antiviral and anti-tumor immunity. We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches.

show abstract

Section: Targeting Enclysis In Autoimmune Liver Diseasementioning

confidence: 99%

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…21 The main treatment methods for acute cholangitis are fluid resuscitation, antibiotic therapy, and biliary drainage. 22 , 23 Antibiotic use and invasive biliary drainage including endoscopic retrograde cholangiopancreatography (ERCP) have been widely reported as possible risk factors for CRO infection. 24 , 25 Therefore, we hypothesized that the analysis of risk factors for CRO infection in patients with acute cholangitis may play a suggestive role in clinical diagnosis and treatment and guide the improvement of prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Biliary stent placement, one of the invasive interventions, may increase the risk of bloodstream infections caused by Enterobacter carbapenem-resistant bacteria. Several studies have indicated that the association of health care exposures and devices with invasive infections in CRO patients has become somewhat of a health consensus in clinical practice (22)(23)(24). Previous studies among hospitalized patients have also explored risk factors for progression from colonization with CRO to invasive infection, and have identified invasive procedures, central line placement, ICU admission, receipt of antibiotics, and underlying diagnoses of diabetes and cancer as risk factors (25-27).…”

mentioning

confidence: 99%

Risk Factors and Prognosis of Carbapenem-Resistant Organism Colonization and Infection in Acute Cholangitis

Jiang

et al. 2022

IDR

View full text Add to dashboard Cite

Background: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis. Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis. Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11-45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11-35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475-17.595, P=0.01) by Cox proportional-hazards regression. Conclusion:Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.

show abstract

“…Many factors contribute to the initiation and pathogenesis of PBC which is reviewed Carbone et al., ( 189 ). The initial insult in PBC is thought to be similar to that of PSC; molecular mimicry by bacterial motifs, subsequently activating the immune response and breaking down self-tolerance.…”

Section: B Cells In Liver Diseasementioning

confidence: 99%

The Role of B Cells in Adult and Paediatric Liver Injury

et al. 2021

View full text Add to dashboard Cite

B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.

show abstract

Primary biliary cholangitis: a multifaceted pathogenesis with potential therapeutic targets

Cited by 19 publications

References 9 publications

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

Risk Factors and Prognosis of Carbapenem-Resistant Organism Colonization and Infection in Acute Cholangitis

The Role of B Cells in Adult and Paediatric Liver Injury

Contact Info

Product

Resources

About