Primary biliary cholangitis: Old and novel therapy

Floreani, Annarosa; Mangini, Chiara

doi:10.1016/j.ejim.2017.06.020

Cited by 62 publications

(47 citation statements)

References 53 publications

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“…As previously mentioned, FGF‐19 expression results directly from FXR activation and leads to downregulation of CYP7A1 . In a phase II multicenter randomized controlled trial of NGM282, a synthetic analogue of FGF‐19 with a modified N terminus, 45 patients with PBC and an incomplete response to UDCA received UDCA plus NGM282 in doses of 0.3 mg or 3.0 mg vs placebo for 28 days.…”

Section: Novel Therapiesmentioning

confidence: 99%

Novel and emerging therapies for cholestatic liver diseases

Goldstein

Levy

2018

Liver International

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While bile acids are important for both digestion and signalling, hydrophobic bile acids can be harmful, especially when in high concentrations. Mechanisms for the protection of cholangiocytes against bile acid cytotoxicity include negative feedback loops via farnesoid X nuclear receptor (FXR) activation, the bicarbonate umbrella, cholehepatic shunting and anti-inflammatory signalling, among others. By altering or overwhelming these defence mechanisms, cholestatic diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) can further progress to biliary cirrhosis, end-stage liver disease and death or liver transplantation. While PBC is currently treated with ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), many fail treatment, and we have yet to find an effective therapy for PSC. Novel therapies under evaluation target nuclear and surface receptors including FXR, transmembrane G-protein-coupled receptor 5 (TGR5), peroxisome proliferator-activated receptor (PPAR) and pregnane X receptor (PXR). Modulation of these receptors leads to altered bile composition, decreased cytotoxicity, decreased inflammation and improved metabolism. This review summarizes our current understanding of the role of bile acids in the pathophysiology of cholestatic liver diseases, presents the rationale for already approved medical therapies and discusses novel pharmacologic therapies under investigation.

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Section: Novel Therapiesmentioning

confidence: 99%

Novel and emerging therapies for cholestatic liver diseases

Goldstein

Levy

2018

Liver International

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“…Ursodeoxycholic acid (UDCA) is the first‐line treatment for PBC . The use of UDCA slows disease progression and improves outcomes, especially in patients with mild histologic changes and good biochemical response . Nevertheless, there is a group of patients with PBC who do not respond optimally to UDCA.…”

mentioning

confidence: 99%

“…(18) The use of UDCA slows disease progression and improves outcomes, especially in patients with mild histologic changes and good biochemical response. (18)(19)(20)(21)(22) Nevertheless, there is a group of patients with PBC who do not respond optimally to UDCA. This prompted a number of efforts to develop additional investigational agents for PBC.…”

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confidence: 99%

Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use

et al. 2019

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“…The first FDA-approved treatment for PBC was UDCA. Approximatively 30–40% of patients fail to respond to UDCA [22]. PBC is usually hard to detect in asymptomatic patients; they rarely visit hospitals to seek diagnosis and therapy until the disease has progressed to a more severe stage.…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

Zheng¹,

Li²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

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Primary biliary cholangitis: Old and novel therapy

Cited by 62 publications

References 53 publications

Novel and emerging therapies for cholestatic liver diseases

Novel and emerging therapies for cholestatic liver diseases

Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use

Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

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