Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach

Mousa, Hani S.; Carbone, Marco; Malinverno, Federica; Ronca, Vincenzo; Gershwin, M. Eric; Invernizzi, Pietro

doi:10.1016/j.autrev.2016.07.003

Cited by 32 publications

(26 citation statements)

References 138 publications

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“…Another disease is primary biliary cirrhosis (PBC) which affects mainly women aged 50-65 years. However, it has been reported that antimitochondrial antibodies, which are very sensitive and specific for PBC, may appear many years before the clinical presentation [50] . The fact that there is a very long period of incubation in some autoimmune diseases, such as PBC, gives rise to the hypothesis that also other autoimmune diseases may start many years before the clinical presentation.…”

Section: Epidemiology and Clinical Presentations Of Some Relevant Autmentioning

confidence: 99%

Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review

Watad¹,

et al. 2017

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Advancements in the field of biomedicine, including the control of infectious diseases through antibiotics and vaccination practices and the prevention of chronic disorders, have led to reduced mortality, increased life expectancy and, as such, growth of the older population. Ageing is accompanied by profound morphological and physiological alterations. In particular, the immune system undergoes a complex series of remodeling/restructuring events, involving almost all compartments - both the innate and the adaptive system. This process is termed immunosenescence or immune dysregulation and, basically, includes 3 events: a reduction in immune response, an increase in the inflammatory and oxidation background (inflammaging and oxi-inflammaging), and a production of autoantibodies. While there is an increase in autoimmunity in the elderly, this does not always translate into an increase in autoimmune diseases, which represent an important cause of morbidity and mortality and affect 5-10% of the world population. Each disease involves a specific age group. Generally speaking, most autoimmune diseases have a decreased peak age of onset, except for very few diseases such as giant cell arteritis and primary biliary cirrhosis, which are more prevalent among the elderly, or inflammatory bowel disease, which has 2 peaks of onset, the first one in young subjects and the other in those older than 60 years. Autoimmune disorders in the elderly have unique clinical presentations, and insidious and atypical symptoms may constitute a challenge for the physician. They are generally milder than in adults and can be controlled by a proper therapeutic treatment. However, despite advancements both in basic and clinical sciences, further studies and investigations are warranted and should be carried out in order to dissect the molecular framework induced by ageing.

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Section: Epidemiology and Clinical Presentations Of Some Relevant Autmentioning

confidence: 99%

Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review

Watad¹,

et al. 2017

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“…Immunosuppressive therapy in PBC in the future may have a role in a disease stage-based approach aiming to reconstitute tolerance by attenuation effector T cell activation, deployment of natural immune checkpoints, or reconstitution of regulatory T cell function [7]. …”

Section: Resultsmentioning

confidence: 99%

“…Biliary epithelial cells are targeted in PBC and express T cell ligands that are thought to be essential for the induction of biliary epithelial autolysis. The highly complex mechanisms for selective biliary cell destruction and potential unique pathways for therapeutic interventions have recently been reviewed [5••6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Why Doesn’t Primary Biliary Cholangitis Respond to Immunosuppressive Medications?

Molinaro

Marschall

2017

Curr Hepatology Rep

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Purpose of ReviewThe purpose of this review is to discuss reasons why immunosuppressive therapy so far failed in Primary Biliry Cholangitis.Recent FindingsEven targeted immunosuppressive therapy seems ineffective or potentially harmful.SummaryBile acid-mediated cholangiocyte damage, facilitated by insufficient bicarbonate secretion, seems to attenuate the anti-inflammatory and anti-fibrotic actions of immunosuppressant and immunomodulatory drugs in a clinically significant way.

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“…without overlap syndromes), glucocorticoids have also demonstrated variable efficacy. Budesonide has proven to be useful in commonly used doses (6‐9 mg daily), with the important caveat that it may not be appropriate for use in cirrhotic patients due to the risk of portal vein thrombosis . Combination therapy with UDCA, azathioprine and prednisolone was examined and showed beneficial effects on albumin and ALP .…”

Section: Experimental Therapies Aimed At the Primary Diseasementioning

confidence: 99%

“…In 2011, a study (NCT01430429) was undertaken to evaluate the safety and efficacy of NI‐0801, an anti‐CXCL monoclonal antibody in PBC patients on UDCA but with incomplete response. The study drug failed to show significant benefit and was subsequently discontinued . IL‐17 inhibition has not yet been studied.…”

Section: Experimental Therapies Aimed At the Primary Diseasementioning

confidence: 99%

Old and new treatments for primary biliary cholangitis

Chascsa

Carey

Lindor

2017

Liver International

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Primary biliary cholangitis (formerly primary biliary cirrhosis) is a rare progressive cholestatic liver disease, whose hallmark features include a persistently elevated alkaline phosphatase level, presence of anti-mitochondrial antibodies and characteristic histology. Since 1998, ursodeoxycholic acid (UDCA), a bile acid, has been the only available therapeutic agent. Primary biliary cholangitis is associated with the development of end-stage liver disease, increased morbidity and mortality. UDCA has been shown to improve serum biochemistries, histology and delay the need for liver transplantation. The clinical issue is that approximately 25%-40% of patients do not respond to this standard therapy. In recent years, many trials have investigated alternative and adjunctive treatments, leading to the recent approval of obeticholic acid, an analogue of chenodeoxycholic acid, which has shown significant and sustained reductions in alkaline phosphatase levels in combination with UDCA. Obeticholic acid has rapidly been embraced as a new agent to improve the biochemical profile in refractory patients, in addition to being approved for use as monotherapy in patients who cannot tolerate UDCA. There are several other studies and targets which are being investigated. This review is intended to highlight the benefits of UDCA, educate the reader on the newly available obeticholic acid, and to summarize the many ongoing trials and therapeutic targets being investigated in attempts to control and cure primary biliary cholangitis.

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Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach

Cited by 32 publications

References 138 publications

Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review

Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review

Why Doesn’t Primary Biliary Cholangitis Respond to Immunosuppressive Medications?

Old and new treatments for primary biliary cholangitis

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