PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales.
AEs, adverse events
AIH, Autoimmune Hepatitis
ALP, Alkaline Phosphatase
AMA, Antimitochondrial antibodies
BZF, Bezafibrate
CKD, chronic kidney disease
Elafibranor
FDA, Food and Drug
FF, Fenofibrate
FXR, Farnesoid X Receptor
Fibrates
GGT, γ-glutamil transferase
HCC, Hepatocellular Carcinoma
HDL, high-density lipoprotein
HR, Hazard Ratio
HSC, Hepatic Stellate Cells
IL-1β, Interleukin-1
IgM, Immunoglobulin M
LDL, low-density- lipoprotein
LT, Liver Transplant
MDR3, multidrug resistance protein 3
NASH, Non Alcoholic Steato-Hepatits
NRS, Numerical Raing Scale
OCA, Obeticholic Acid
OR, Odds Ratio
PAR, protease-activated receptors
PBC, Primary Biliary Cholangitis
PC, phosphatidylcholine
PH, Portal Hypertension
PPAR agonists
PPAR, peroxisome proliferator-activated receptor
Primary biliary cholangitis
QoL, Quality of Life
RCT, randomized controlled trial
SAE, Severe Adverse Event
Saroglitazar
Seladelpar
TGR, transmembrane G protein-coupled receptor
TLR, Toll Like Receptor
TNF-α, Tumor Necrosis Factor- α
UDCA
UDCA, ursodeoxycholic acid
UK, United Kingdom
ULN, upper limit of normal
VAS, Visual Analogue Scale
VRS, Verbal Rating Scale
Journal
Journal of translational autoimmunity
ISSN: 2589-9090
Titre abrégé: J Transl Autoimmun
Pays: Netherlands
ID NLM: 101759413
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
12
2022
revised:
30
12
2022
accepted:
02
01
2023
entrez:
23
1
2023
pubmed:
24
1
2023
medline:
24
1
2023
Statut:
epublish
Résumé
Primary biliary cholangitis (PBC) is an autoimmune liver disease involving the small intrahepatic bile ducts; when untreated or undertreated, it may evolve to liver fibrosis and cirrhosis. Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA. However, due to moderate rate of UDCA-non responders and to warnings recently issued against OCA use in patients with cirrhosis, further therapies are needed.Areas covered. Deep investigations into the pathogenesis of PBC is leading to proposal of new therapeutic agents, among which peroxisome proliferator-activated receptor (PPAR) ligands seem to be highly promising given the preliminary, positive results in Phase 2 and 3 trials. Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers. We herein describe completed and ongoing trials involving PPAR agonists use in PBC, analyzing pits and falls. Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.
Identifiants
pubmed: 36684809
doi: 10.1016/j.jtauto.2023.100188
pii: S2589-9090(23)00001-1
pmc: PMC9850184
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
100188Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ana Lleo reports a relationship with Gilead Sciences Inc that includes: speaking and lecture fees. Ana Lleo reports a relationship with Intercept Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Ana Lleo reports a relationship with Alfasigma SpA that includes: consulting or advisory and speaking and lecture fees. Ana Lleo reports a relationship with Albireo Pharma Inc that includes: consulting or advisory. Ana Lleo reports a relationship with GSK that includes: speaking and lecture fees. Ana Lleo reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Ana Lleo reports a relationship with Incyte Corporation that includes: speaking and lecture fees. Ana Lleo reports a relationship with Takeda Pharmaceutical Co Ltd that includes: consulting or advisory. Ana Lleo reports a relationship with Kowa Pharmaceutical Europe Co Ltd that includes: consulting or advisory. Ana Lleo reports a relationship with Merck Sharp & Dohme UK Ltd that includes: speaking and lecture fees. Ana Lleo reports a relationship with AbbVie Inc that includes: speaking and lecture fees. Francesca Colapietro reports a relationship with Intercept Pharmaceuticals Inc that includes: speaking and lecture fees. Research Grants: EU Project D-LIVER, EU COST Action EURO-Cholangio-Net, Italian Ministry of Health, Italian Association for Cancer Research (AIRC) Support for sponsored studies (via Humanitas Research Hospital): Falk, Intercept Pharma.
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