keyword
https://read.qxmd.com/read/38506926/primary-biliary-cholangitis-drug-evaluation-and-regulatory-approval-where-do-we-go-from-here
#1
JOURNAL ARTICLE
David Ej Jones, Ulrich Beuers, Alan Bonder, Marco Carbone, Emma Culver, Jessica Dyson, Robert G Gish, Bettina E Hansen, Gideon Hirschfield, Rebecca Jones, Kris Kowdley, Andreas E Kremer, Keith Lindor, Marlyn Mayo, George Mells, James Neuberger, Martin Prince, Mark Swain, Atsushi Tanaka, Douglas Thorburn, Michael Trauner, Palak Trivedi, Martin Weltman, Andrew Yeoman, Cynthia Levy
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of Ursodeoxycholic Acid (UDCA). Up to 40% of patients do not, however, respond adequately to UDCA and therefore still remain at risk of disease progression to cirrhosis. The introduction of Obeticholic acid (OCA) as second-line therapy for patients failing UDCA has improved outcomes for PBC patients. There remains, however, a need for better treatments for higher risk patients...
March 20, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://read.qxmd.com/read/38485279/-cyp7a1-gene-induction-via-shp-dependent-or-independent-mechanisms-can-increase-the-risk-of-drug-induced-liver-injury-independently-or-in-synergy-with-bsep-inhibition
#2
JOURNAL ARTICLE
Congrong Niu, Xiaodong Xie, Renmeng Liu, Xiaomin Liang, Yiding Hu, Yurong Lai
Drug-induced liver injury (DILI) is a frequent cause of clinical trial failures during drug development. While inhibiting BSEP is a well-documented DILI mechanism, interference with genes related to bile acid (BA) metabolism and transport can further complicate DILI development. Here, the effects of twenty-eight compounds on genes associated with BA metabolism and transport were evaluated, including those with discontinued development or use, boxed warnings, and clean labels for DILI. The study also included rifampicin and omeprazole, PXR and AhR ligands, and four mitogen-activated protein kinase kinase (MEK1/2) inhibitors...
March 14, 2024: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://read.qxmd.com/read/38481550/hepatic-transcriptome-discloses-the-potential-targets-of-xuefu-zhuyu-decoction-ameliorating-non-alcoholic-fatty-liver-disease-induced-by-high-fat-diet
#3
JOURNAL ARTICLE
Hao Tang, Jun Wang, Yi Fang, Yixiao Yin, Wei Liu, Yiyang Hu, Jinghua Peng
BACKGROUND AND AIM: Xuefu Zhuyu decoction (XZD), a traditional Chinese medicinal formula, was firstly recorded in the Qing dynasty of ancient China and previously demonstrated to ameliorate hepatic steatosis. In the present study, the effects of XZD on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) were evaluated in mice and the hepatic transcriptome was detected to disclose the potential mechanisms of XZD. EXPERIMENTAL PROCEDURE: The effects of XZD (low- and high-dosage) on NAFLD induced by HFD for 16 weeks were evaluated...
March 2024: Journal of Traditional and Complementary Medicine
https://read.qxmd.com/read/38478331/comparative-efficacy-of-drug-interventions-on-nafld-over-24-weeks-a-traditional-and-network-meta-analysis-of-randomized-controlled-trials
#4
Yifan Wang, He Yi, Weixia Sun, Hekai Yu, Wenxuan Tao, Xiaojin Yu, Dianrong Jia, Yingzhao Liu, Stephen J Pandol, Ling Li
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects approximately 38% of the world's population, yet no pharmacological therapies have been approved for treatment. We conducted a traditional and network meta-analysis to comprehensively assess the effectiveness of drug regimens on NAFLD, and continued to use the old terminology for consistency. METHODS: Randomized, placebo-controlled trials (RCTs) investigating drug therapy in an adult population diagnosed with NAFLD with or without diabetes mellitus were included...
March 13, 2024: Drugs
https://read.qxmd.com/read/38469871/emerging-drugs-for-the-treatment-of-hepatic-fibrosis-on-nonalcoholic-steatohepatitis
#5
REVIEW
Michihiro Iwaki, Masato Yoneda, Naohiro Wada, Otani Tomohiro, Takashi Kobayashi, Asako Nogami, Satoru Saito, Nakajima Atsushi
INTRODUCTION: Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important. AREAS COVERED: This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis. EXPERT OPINION: Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways...
March 12, 2024: Expert Opinion on Emerging Drugs
https://read.qxmd.com/read/38458248/bioprotective-role-of-phytocompounds-against-the-pathogenesis-of-non-alcoholic-fatty-liver-disease-to-non-alcoholic-steatohepatitis-unraveling-underlying-molecular-mechanisms
#6
JOURNAL ARTICLE
Tanmoy Banerjee, Arnab Sarkar, Sk Zeeshan Ali, Rudranil Bhowmik, Sanmoy Karmakar, Amit Kumar Halder, Nilanjan Ghosh
Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build-up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions...
March 8, 2024: Planta Medica
https://read.qxmd.com/read/38451288/-primary-biliary-cholangitis-response-criteria-of-first-line-treatment-and-perspectives-of-second-line-therapy
#7
REVIEW
Silja Steinmann, Christoph Schramm
BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that can progress to liver cirrhosis if left untreated. Early diagnosis, initiation of therapy and, if necessary, adjustment of treatment are essential to prevent disease progression. The timing and thresholds for assessing adequate treatment response are inconsistently defined in the literature and can pose a challenge in clinical practice. OBJECTIVE: In addition to providing a concise overview of the guideline-based diagnostic work-up and first-line therapy, this study offers practical guidance for the evaluation of treatment response and options for second-line treatment in PBC...
March 7, 2024: Inn Med (Heidelb)
https://read.qxmd.com/read/38447019/predictive-factors-for-decompensating-events-in-cirrhotic-patients-with-primary-biliary-cholangitis-under-different-lines-of-therapy
#8
JOURNAL ARTICLE
Javier Ampuero, Ana Lucena, Marina Berenguer, Manuel Hernández-Guerra, Esther Molina, Judith Gómez-Camarero, Carlos Valdivia, Elena Gómez, Marta Casado, Carmen Álvarez-Navascuez, Francisco Jorquera, Luisa García-Buey, Álvaro Díaz-González, Rosa Morillas, Montserrat García-Retortillo, Jose Manuel Sousa, Indhira Pérez-Medrano, Miguel Ángel Simón, Javier Martínez, Juan Arenas, María Carlota Londoño, Antonio Olveira, Conrado Fernández-Rodríguez
BACKGROUND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world cirrhotic PBC population, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH RESULTS: Multicenter study enrolling 388 PBC-cirrhotic patients from the Spanish ColHai registry...
March 6, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://read.qxmd.com/read/38442444/baicalein-alleviates-intrahepatic-cholestasis-by-regulating-bile-acid-metabolism-via-an-fxr-dependent-manner
#9
JOURNAL ARTICLE
Weifan Huang, Yihan Qian, Jiacheng Lin, Fang Wang, Xiaoni Kong, Weifeng Tan
Cholestasis is characterized by impaired bile secretion and flow, leading to the accumulation of toxic bile acids in the liver, further causing inflammatory reaction, fibrosis, and ultimately liver transplantation. Although first-line clinical agents such as Ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) are available, serious side effects still exist. Therefore, pharmacologic treatment of cholestatic liver disease remains challenging. Here, we used a murine model of cholestasis treated with or without intraperitoneal injection of baicalein and found that baicalein could attenuate 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammatory response, ductular reaction, liver fibrosis, and bile acid metabolism disorders...
February 17, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38378873/inflammation-drives-pathogenesis-of-early-intestinal-failure-associated-liver-disease
#10
JOURNAL ARTICLE
Scott C Fligor, Savas T Tsikis, Thomas I Hirsch, Ashish Jain, Liang Sun, Shira Rockowitz, Kathleen M Gura, Mark Puder
Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days...
February 20, 2024: Scientific Reports
https://read.qxmd.com/read/38363900/the-effect-and-safety-of-obeticholic-acid-for-patients-with-nonalcoholic-steatohepatitis-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#11
JOURNAL ARTICLE
Jie Zhao, Baozhen Li, Kai Zhang, Zhiyong Zhu
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia. METHOD: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients...
February 16, 2024: Medicine (Baltimore)
https://read.qxmd.com/read/38328407/dachaihu-decoction-inhibits-hypernutrition-induced-liver-metastasis-from-colorectal-cancer-by-maintaining-the-gut-vascular-barrier
#12
JOURNAL ARTICLE
Ruolei Wang, Fengjing Jia, Zhenguo Zhao, Liqing Du, Lianheng Lu, Dongkui Xu, Feng He
BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC...
April 2023: Cancer Pathog Ther
https://read.qxmd.com/read/38307734/treatment-in-primary-biliary-cholangitis-beyond-ursodeoxycholic-acid
#13
REVIEW
M C van Hooff, E Werner, A J van der Meer
Primary biliary cholangitis (PBC) is a rare cholestatic immune-mediated liver disease. The clinical course varies from mild to severe, with a substantial group of patients developing cirrhosis within a decade. These patients are at risk of hepatocellular carcinoma, decompensation and liver failure. First line Ursodeoxycholic acid (UDCA) treatment improves the cholestatic surrogate markers, and was recently associated with a favorable survival free of liver transplantation, even in case of an incomplete biochemical response...
February 2, 2024: European Journal of Internal Medicine
https://read.qxmd.com/read/38302816/the-obeticholic-acid-can-positively-regulate-the-cancerous-behavior-of-mcf7-breast-cancer-cell-line
#14
JOURNAL ARTICLE
Reza Rahmani, Neda Eivazi, Solaleh Emamgholipour, Mahdi Aminian, Ali Jalilian, Maliheh Paknejad
BACKGROUND: The diagnosis and treatment processes of cancer are among the main challenges of medical science in recent decades. The use of different therapeutic agents is one of the most common methods frequently utilized for cancer treatment. Accumulating evidence points to a potential effect of Obeticholic acid (OCA), a specific ligand for farnesoid X receptor, on the regulation of cancer-associated pathways. In spite of tremendous efforts to introduce OCA into the clinical setting, there is a great deal of uncertainty about its impact on breast cancer treatment...
February 1, 2024: Molecular Biology Reports
https://read.qxmd.com/read/38293761/safety-pharmacokinetics-and-pharmacodynamics-of-obeticholic-acid-in-subjects-with-fibrosis-or-cirrhosis-from-nash
#15
JOURNAL ARTICLE
Naim Alkhouri, Carl LaCerte, Jeffrey Edwards, Fred Poordad, Eric Lawitz, Lois Lee, Sharon Karan, Sangeeta Sawhney, Mary Erickson, Leigh MacConell, Luna Zaru, Jianfen Chen, Jason Campagna
BACKGROUND & AIMS: Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis. METHODS: Study 747-117 randomized 51 subjects with NASH (fibrosis stages F1-F4) to daily placebo, OCA 10 or OCA 25 mg (1:2:2) for 85 days. Study 747-118 randomized 24 subjects with NASH cirrhosis (F4; Child-Pugh [CP]-A) and normal liver control subjects matched for similar body weight to daily OCA 10 or OCA 25 mg (1:1) for 28 days...
January 31, 2024: Liver International: Official Journal of the International Association for the Study of the Liver
https://read.qxmd.com/read/38285279/edaravone-and-obeticholic-acid-protect-against-cisplatin-induced-heart-toxicity-by-suppressing-oxidative-stress-and-inflammation-and-modulating-nrf2-tlr4-p38mapk-and-jak1-stat3-nf-%C3%AE%C2%BAb-signals
#16
JOURNAL ARTICLE
Ehab A M El-Shoura, Emad H M Hassanein, Hesham H Taha, Abdel-Gawad S Shalkami, Mohamed Mahmoud Hussein Hassanein, Fares E M Ali, Adel G Bakr
Cardiotoxicity is a significant adverse effect of cisplatin (CIS) that necessitates extensive medical care. The current study examines the cardioprotective effects of edaravone (EDV), obeticholic acid (OCA), and their combinations on CIS-induced cardiac damage. Rats were allocated into five groups: the normal control group, the remaining four groups received CIS (7.5 mg/kg, i.p.) as a single dose on the fifth day and were assigned to CIS, OCA (10 mg/kg/day) + CIS, EDV (20 mg/kg/day) + CIS, and the (EDV + OCA) + CIS group...
January 29, 2024: Naunyn-Schmiedeberg's Archives of Pharmacology
https://read.qxmd.com/read/38196299/hepatic-accumulated-obeticholic-acid-and-atorvastatin-self-assembled-nanocrystals-potentiate-ameliorative-effects-in-treatment-of-metabolic-associated-fatty-liver-disease
#17
JOURNAL ARTICLE
Huanfen Lu, Zhenglan Ban, Kai Xiao, Madi Sun, Yongbo Liu, Fangman Chen, Tongfei Shi, Li Chen, Dan Shao, Ming Zhang, Wei Li
Exploration of medicines for efficient and safe management of metabolic-associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic-targeted nanodrugs composed of OCA and cholesterol-lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created...
January 9, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38178006/pharmacotherapy-for-primary-biliary-cholangitis-an-assessment-of-medication-candidacy-and-rates-of-treatment
#18
JOURNAL ARTICLE
Nicholas MacDonald, Rebecca Loh, Jonathan M Fenkel, David A Sass, Dina Halegoua-DeMarzio
BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis...
January 4, 2024: BMC Gastroenterology
https://read.qxmd.com/read/38104861/obeticholic-acid-protects-against-lithocholic-acid-induced-exogenous-cell-apoptosis-during-cholestatic-liver-injury
#19
JOURNAL ARTICLE
Qian Lu, Yangping Zhu, Changling Wang, Rongmi Zhang, Yingying Miao, Yuanyuan Chai, Zhenzhou Jiang, Qinwei Yu
AIMS: Lithocholic acid (LCA)-induced cholestasis was accompanied by the occurrence of apoptosis, which indicated that anti-apoptosis was a therapeutic strategy for primary biliary cholangitis (PBC). As an agonist of (Farnesoid X receptor) FXR, we supposed that the hepatoprotection of Obeticholic acid (OCA) against cholestatic liver injury is related to anti-apoptosis beside of the bile acids (BAs) regulation. Herein, we explored the non-metabolic regulating mechanism of OCA for resisting LCA-induced cholestatic liver injury via anti-apoptosis...
December 15, 2023: Life Sciences
https://read.qxmd.com/read/38089546/critical-shortfalls-in-the-management-of-pbc-results-of-a-uk-wide-population-based-evaluation-of-care-delivery
#20
JOURNAL ARTICLE
Nadir Abbas, Rachel Smith, Steven Flack, Vikram Bains, Richard J Aspinall, Rebecca L Jones, Laura Burke, Douglas Thorburn, Michael Heneghan, Andrew Yeoman, Joanna Leithead, Conor Braniff, Andrew Robertson, Chris Mitchell, Collette Thain, Robert Mitchell-Thain, David Jones, Palak J Trivedi, George F Mells, Laith Alrubaiy
BACKGROUND & AIMS: Guidelines for the management of primary biliary cholangitis (PBC) were published by the British Society of Gastroenterology in 2018. In this study, we assessed adherence to these guidelines in the UK National Health Service (NHS). METHODS: All NHS acute trusts were invited to contribute data between 1 January 2021 and 31 March 2022, assessing clinical care delivered to patients with PBC in the UK. RESULTS: We obtained data for 8,968 patients with PBC and identified substantial gaps in care across all guideline domains...
January 2024: JHEP reports: innovation in hepatology
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