- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Farnesoid X receptor regulates PIK/AKT/mTOR signaling pathway, lipid metabolism, and immune response in hybrid grouper. (Pubmed Central) - Oct 11, 2022
In vivo and vitro, activation of FXR by obeticholic acid (OA) significantly increased the concentrations and mRNA levels of hepatic inflammatory cytokines...In addition, the inhibition of FXR activated the PIK/AKT/mTOR pathway, decreased the lipolysis and increased the lipogenesis, and subsequently increased the lipid accumulation in fish. These results revealed the positive roles of FXR in triggering immune responses and improving lipid metabolism and accumulation in hybrid grouper.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Observational data, Journal, Real-world evidence: Medication adherence to obeticholic acid: a real-world experience using medication event monitoring systems. (Pubmed Central) - Oct 9, 2022
These results revealed the positive roles of FXR in triggering immune responses and improving lipid metabolism and accumulation in hybrid grouper. We expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor compliance and introduce measures to reduce its prevalence.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, aldafermin (NGM282) / NGM Biopharma
Preclinical, Journal: Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice. (Pubmed Central) - Sep 29, 2022
In a second (wild-type) mouse model, a combination of obeticholic acid (OCA) and intestine-restricted ASBT inhibition was used to lower the bile salt pool size before BDL...Novel treatment approaches against cholestatic liver disease (resulting in reduced or blocked flow of bile) involve non-absorbable inhibitors of the bile acid transport protein ASBT, but these are not always effective and/or can cause unwanted side effects. In this study, we demonstrate that systemic inhibition/inactivation of ASBT protects mice against developing severe cholestatic liver injury after bile duct ligation, by reducing bile salt pool size and increasing renal bile salt excretion.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Bezalip SR (bezafibrate) / AbbVie, Intercept, Miravo
Trial completion date, Trial primary completion date, Combination therapy: Study of OCA in Combination with BZF Evaluating Efficacy, Safety, and Tolerability in Participants with PBC (clinicaltrials.gov) - Sep 29, 2022
P2, N=75, Recruiting,
Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use. Trial completion date: Jun 2023 --> Sep 2024 | Trial primary completion date: Jul 2022 --> Sep 2023
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Enrollment open, Trial initiation date: Testing Obeticholic Acid for Familial Adenomatous Polyposis (clinicaltrials.gov) - Sep 28, 2022
P2a, N=60, Recruiting,
Trial completion date: Jun 2023 --> Sep 2024 | Trial primary completion date: Jul 2022 --> Sep 2023 Not yet recruiting --> Recruiting | Initiation date: Dec 2022 --> Sep 2022
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: SARS-CoV-2 vaccine, a new autoimmune hepatitis trigger? (Pubmed Central) - Sep 20, 2022
Male, 76 years old, with a history of hepatic cirrhosis secondary to primary biliary cholangitis (PBC), compensated, treated with ursodeoxycholic acid and obeticholic acid...The patient was diagnosed with AIH and initiated therapy with steroids and azathioprine, currently with an adequate response...Therefore, it is suggested that vaccination can induce the development of autoimmune pathology in patients at risk. Our reported case reinforces the hypothesis of an association between AIH and the SARS-CoV2 vaccine.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Gypenosides ameliorate high-fat diet-induced non-alcoholic steatohepatitis via farnesoid X receptor activation. (Pubmed Central) - Sep 14, 2022
A mouse model of HFD-induced NSAH was used to examine effects of Gyps on NASH with obeticholic acid (OCA) as a positive control, and the role of FXR in its mechanism of action was investigated in wild-type (WT) and FXR knockout (KO) mice...Notably, Gyps- and OCA-mediated pharmacological effects were significantly abrogated by depletion of the FXR gene in FXR KO mice. Gyps ameliorated HFD-induced NASH through the direct activation of FXR and FXR-dependent signaling pathways.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Review, Journal: The Bile Acid Membrane Receptor TGR5 in Cancer: Friend or Foe? (Pubmed Central) - Sep 3, 2022
Several recent studies have demonstrated that TGR5 exerts inconsistent effects in different cancer cells upon activating via TGR5 agonists, such as INT-777, ursodeoxycholic acid (UDCA), and taurolithocholic acid (TLCA). In this review, we discuss both the 'friend' and 'foe' features of TGR5 by summarizing its tumor-suppressing and oncogenic functions and mechanisms.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date, Real-world evidence, Real-world: HEROES PBC: A Real-World Data Study to Evaluate the Effectiveness of OCA on Hepatic Outcomes in PBC Patients (clinicaltrials.gov) - Sep 1, 2022
P=N/A, N=2350, Enrolling by invitation,
Furthermore, potential metabolites have been synthesized, characterized and evaluated for their ability to modulate FXR and TGR5 receptors providing key reference standards for future drug investigations, as well as offering further insights into the structure-activity relationships of this class of compounds. Trial completion date: Jul 2022 --> Oct 2022 | Trial primary completion date: Jun 2022 --> Sep 2022
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Update on the Pharmacological Treatment of Primary Biliary Cholangitis. (Pubmed Central) - Aug 27, 2022
Ursodeoxycholic acid (UDCA) is the first-line therapy used for the treatment of PBC...Obeticholic acid (OCA) is registered in many countries for PBC, and fibrates also seem to be effective in ameliorating biochemistry alteration and symptoms typical of PBC...Since an insufficient amount of data is currently available about the effect of these novel approaches on robust clinical endpoints, such as transplant-free survival, their clinical approval needs to be supported by the consistent improvement of these parameters. The intensive research in this field will hopefully lead to a novel treatment landscape for PBC in the near future, with innovative therapies based on the combination of multiple agents acting on different pathogenetic mechanisms.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver. (Pubmed Central) - Aug 24, 2022
Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: UK-Wide Multicentre Evaluation of Second Line Therapies in Primary Biliary Cholangitis. (Pubmed Central) - Aug 13, 2022
Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada. Across the UK-PBC population, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review). (Pubmed Central) - Aug 13, 2022
In the present review, the structure and function of BAs were introduced and the metabolism of BAs and the process of enterohepatic circulation were outlined. Furthermore, the mechanisms by which BAs participate in the development of HCC were summarized and possible strategies for targeting BAs and key sites of their metabolic processes to treat HCC were suggested.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Review, Journal: Animal Models for Autoimmune Hepatitis: Are Current Models Good Enough? (Pubmed Central) - Aug 6, 2022
However, there are other factors, such as housing conditions, nutrition, and the microbiome that might also play an important role. This review will predominantly focus on the current status of animal models for autoimmune hepatitis and the possible ways to overcome discrepancies between model and patient.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Potential mesenchymal stem cell therapeutics for treating primary biliary cholangitis: advances, challenges, and perspectives. (Pubmed Central) - Aug 6, 2022
In this review, we characterized the underlying roles and mechanisms of MSCs for treating liver diseases and highlight recent basic and clinical advances in MSC-based therapy for treating PBC. Finally, the current challenges and perspectives for MSC-based therapy in clinical application are discussed, which could help accelerate the application of MSCs in clinical practice, especially for refractory diseases such as PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: PPARα: A potential therapeutic target of cholestasis. (Pubmed Central) - Aug 5, 2022
In addition, the anti-inflammatory effects of PPARα will be discussed in some detail. Finally, we will discuss the application of PPARα agonists for cholestatic liver disorders.
- |||||||||| Prolia (denosumab) / Amgen, Daiichi Sankyo, Ocaliva (obeticholic acid) / Intercept, Invokana (canagliflozin) / J&J, Daiichi Sankyo, Mitsubishi Tanabe
Review, Journal: Nonalcoholic fatty liver disease and osteoporosis: a potential association with therapeutic implications. (Pubmed Central) - Aug 5, 2022
If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarized the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focused on treatment considerations derived from this potential association.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion, Enrollment change, Real-world evidence, Real-world: HEROES PBC: Real-World Data Study to Evaluate the Effectiveness of OCA on Hepatic Outcomes in PBC Patients (clinicaltrials.gov) - Aug 2, 2022
P=N/A, N=4937, Completed,
This review summarized the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focused on treatment considerations derived from this potential association. Enrolling by invitation --> Completed | N=3156 --> 4937
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Lactational delivery of Triclosan promotes non-alcoholic fatty liver disease in newborn mice. (Pubmed Central) - Jul 30, 2022
The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. It is yet to be investigated but mother to child transmission of TCS or similar toxicants may underlie the recent increases in pediatric NAFLD.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis. (Pubmed Central) - Jul 27, 2022
In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus...It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Diminished tubule epithelial farnesoid X receptor expression exacerbates inflammation and fibrosis response in aged rat kidney. (Pubmed Central) - Jul 23, 2022
The activation of FXR by obeticholic acid significantly reduced the transcriptional activity of NF-κB and chemokine production...Finally, FXR-knockout mice that were administered folic acid showed increased inflammation and severe fibrosis. In summary, we demonstrated that diminished FXR expression in the epithelial cells of the renal tubules exacerbated the fibrotic response in aged rat kidneys by upregulating pro-inflammatory NF-κB activation.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Structural basis and molecular mechanism of biased GPBAR signaling in regulating NSCLC cell growth via YAP activity. (Pubmed Central) - Jul 23, 2022
Here, via functional screening, we found that two specific GPBAR agonists, R399 and INT-777, demonstrated strikingly different regulatory effects on the growth and apoptosis of non-small cell lung cancer (NSCLC) cells both in vitro and in vivo...In summary, we demonstrate that different agonists can regulate distinct functions of cell growth and apoptosis through biased GPBAR signaling and control of YAP activity in a NSCLC cell model. The delineated mechanism and structural basis may facilitate the rational design of GPBAR-targeting drugs with both metabolic and anticancer benefits.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Mechanisms & Molecules: What are the treatment targets for PBC? (Pubmed Central) - Jul 23, 2022
Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well-tolerated by patients with significant itch or advanced cirrhosis...No abstract available
- |||||||||| Ocaliva (obeticholic acid) / Intercept
HEPATOBILIARY DISORDERS IN INFLAMMATORY BOWEL DISEASE: WHAT COULD BE THE OPTIMAL MANAGEMENT WHEN PRIMARY BILIARY CHOLANGITIS PRECEDES THE ONSET OF CROHN ILEITIS? A SIXTY-SIX YEARS OLD FEMALE PATIENT CASE REPORT (Science Lounge) - Jul 20, 2022 - Abstract #UEGW2022UEGW_2730;
This study established the importance of microbial mechanism and its inhibition as a potential therapeutic target to treat Meth-related hepatotoxicity. Clinical Case Summary: Hepatobiliary disorders’ association with inflammatory bowel diseases (IBDs) has been widely proven.However, the concomitance of Primary Biliary Cholangitis (PBC) and Crohn’s disease (CD) is anecdotical, usually described in male young patients with a diagnosis of IBD preceding the onset of PBC.We report the case of a 66-year-old female patient with pre-existent PBC at the moment of the CD-ileitis identification.She was admitted for recurrent abdominal colic pain and irrepressible chronic diarrhea; her family history didn’t reveal any inflammatory or neoplastic gut disorders; PBC and Hashimoto’s thyroiditis were the highlighted comorbidities.PBC was diagnosed 5 years before,treated for two years with the administration of 15 mg/Kg/die ursodeoxycholic acid (UDCA) which,because of the severe diarrhea, was then stopped.After an inconclusive chronic diarrhea diagnostic work-up (table), further examinations were performed, including colonoscopy and MRI-enterography, both assessing a picture suitable for CD.The combination of the clinical, endoscopic, and radiologic findings realized the final diagnosis of Crohn’s Ileitis causing ileal substenosis in a patient with PBC.Given the UDCA intolerance,an oral monotherapy treatment using obeticholic acid 5 mg/die was prescribed.Considering the concomitant diagnosis of ileal-CD and the potential benefits described as off-label therapy on PBC patients,budesonide 9 mg/die per os was also administered.One month after discharge, an improvement was observed both in cholestasis indexes and gastrointestinal symptoms.According to our experience, all IBD patients should be constantly screened for hepatobiliary manifestations, to provide an early setting of a tailored therapeutic path.Table >
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