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Tatsuo Kanda, Shin Yasui, Masato Nakamura, Shingo Nakamoto, Koji Takahashi, Shuang Wu, Reina Sasaki, Yuki Haga, Sadahisa Ogasawara, Tomoko Saito, Kazufumi Kobayashi, Soichiro Kiyono, Yoshihiko Ooka, Eiichiro Suzuki, Tetsuhiro Chiba, Hitoshi Maruyama, Fumio Imazeki, Mitsuhiko Moriyama, Naoya Kato
Background: Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results: All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR...
February 20, 2018: Oncotarget
Chen-Yi Liao, Chi-Hsiang Chung, Pauling Chu, Kuang-Yu Wei, Tseng-Min Feng, Fu-Huang Lin, Chang-Huei Tsao, Chia-Chao Wu, Wu-Chien Chien
BACKGROUND: We evaluated the risk of osteoporosis in patients with primary biliary cirrhosis (PBC) using a nationwide population-based dataset. METHODS: In a cohort study of 986,713 individuals, we selected 2,493 PBC patients who were aged 18 years or older and had been diagnosed with PBC, based on the International Classification of Disease (ICD-9-CM) codes 571.6, during 20002010. The control cohort comprised 9,972 randomly selected, propensity matched patients (by age, gender, and index date), without PBC...
2018: PloS One
Fabio Tonin, Isabel W C E Arends
Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products...
2018: Beilstein Journal of Organic Chemistry
Jialin Sun, Menghua Li, Shiyong Fan, Zhongwu Guo, Bohua Zhong, Xueyuan Jin, Weiguo Shi
Portal hypertension (PHT) is a common liver disease that is closely related to cirrhosis and has a high morbidity and mortality. The present study aimed to probe the efficacy of a novel nitric oxide (NO)-releasing agent with NO linked to ursodeoxycholic acid (UDCA) through threonine (UDCA-Thr-NO) as a liver-targeted therapy for cirrhosis and PHT. After intraperitoneal treatment of dimethyl nitrosamine-induced cirrhotic rats for 3 or 4 weeks, UDCA-Thr-NO could prevent ascites formation and reduce portal pressure instead of carotid artery pressure, when compared with UDCA or compound embryonic bovine liver extract tablets...
2018: American Journal of Translational Research
Machelle T Pardue, Rachael S Allen
Diseases that affect the eye, including photoreceptor degeneration, diabetic retinopathy, and glaucoma, affect 11.8 million people in the US, resulting in vision loss and blindness. Loss of sight affects patient quality of life and puts an economic burden both on individuals and the greater healthcare system. Despite the urgent need for treatments, few effective options currently exist in the clinic. Here, we review research on promising neuroprotective strategies that promote neuronal survival with the potential to protect against vision loss and retinal cell death...
February 23, 2018: Progress in Retinal and Eye Research
Alzbeta Horvatova, Tanyarath Utaipan, Ann-Christin Otto, Yuling Zhang, Hongying Gan-Schreier, Petr Pavek, Anita Pathil, Wolfgang Stremmel, Walee Chamulitrat
The bile acid-phospholipid conjugate ursodeoxycholyl oleoyl-lysophophatidylethanolamide (UDCA-18:1LPE) is an anti-inflammatory and anti-fibrotic agent as previously shown in cultured hepatocytes and hepatic stellate cells as well as in in vivo models of liver injury. We hypothesize that UDCA-18:1LPE may directly inhibit the activation of immune cells. We found that UDCA-18:1LPE was capable of inhibiting the migration of phorbol ester-differentiated human THP-1 cells. We examined anti-inflammatory activity of UDCA-18:1LPE during activation of THP1-derived macrophages...
February 20, 2018: European Journal of Pharmacology
Xin Yan, Jinglan Jin
RATIONALE: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. PATIENT CONCERNS: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department...
February 2018: Medicine (Baltimore)
Diego Andrés Rodríguez Lugo, Jorge Julián Coronado Tovar, Giovana Alejandra Solano Villamarin, Wiliam Otero Regino
Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others...
October 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
Bigina N R Ginos, Sandi L Navarro, Yvonne Schwarz, Haiwei Gu, Dongfang Wang, Timothy W Randolph, Ali Shojaie, Meredith A J Hullar, Paul D Lampe, Mario Kratz, Marian L Neuhouser, Daniel Raftery, Johanna W Lampe
OBJECTIVE: The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS: We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18...
February 16, 2018: Metabolism: Clinical and Experimental
Xiang Jiang, Min Lian, Yanmei Li, Weici Zhang, Qixia Wang, Yiran Wei, Jun Zhang, Weihua Chen, Xiao Xiao, Qi Miao, Zhaolian Bian, Dekai Qiu, Jingyuan Fang, Aftab A Ansari, Patrick S C Leung, Ross L Coppel, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored...
February 8, 2018: Journal of Autoimmunity
Linlin Zhang, Huizong Su, Yue Li, Yujuan Fan, Qian Wang, Jian Jiang, Yiyang Hu, Gaofeng Chen, Bo Tan, Furong Qiu
The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg-1, ig) for 12 days prior to ANIT administration (50 mg·kg-1, ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (β-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed...
February 1, 2018: Toxicology and Applied Pharmacology
Atsushi Tanaka, Junko Hirohara, Toshiaki Nakano, Minami Yagi, Tadashi Namisaki, Hitoshi Yoshiji, Yasuni Nakanuma, Hajime Takikawa
BACKGROUND: As primary biliary cholangitis (PBC) is a heterogeneous disease, we hypothesized that there is a population of patients with early PBC who do not need prompt treatment with ursodeoxycholic acid (UDCA). AIMS: In this study, we analyzed data from a large-scale PBC cohort in Japan, and retrospectively investigated whether outcomes of early PBC patients were affected with prompt or deferred/no UDCA treatment. METHODS: We defined early PBC as asymptomatic, serum alkaline phosphatase <1...
February 6, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
Qin Li, Amal Dutta, Charles Kresge, Abhijit Bugde, Andrew P Feranchak
Bile acids stimulate a bicarbonate-rich choleresis in part through effects on cholangiocytes. As Cl- channels in the apical membrane of cholangiocytes provide the driving force for secretion and TMEM16A has been identified as the Ca2+ -activated Cl- channel in the apical membrane of cholangiocytes (1), the aim of the present study was to determine if TMEM16A is the target of bile acid-stimulated Cl- secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to Ursodeoxycholic acid (UDCA) or Tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl- permeability, and transepithelial secretion...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sanjay U Nipanikar, Sohan S Chitlange, Dheeraj Nagore
Background: Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe. Objective: Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats...
December 2017: Pharmacognosy Research
Y W Shi, H Ma
With the progress in detection methods and the update of diagnostic and therapeutic concepts, more and more patients with primary biliary cholangitis (PBC) have been diagnosed and treated. A high proportion of PBC patients, however, progress to liver decompensation, with an increased risk of liver transplantation and death and a significant reduction in long-term survival. These patients need early diagnosis and urgent treatment. This article discusses how to identify the PBC patients with poor prognosis early from the aspects of biochemical response, disease features, and biomarkers, and reviews the progress in related complementary therapies and new drugs including Ocaliva, Fibrates, UDCA-derived drugs, and molecular targeted drugs...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Y M Li, Q X Wang, X Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
F Ferrari, G Ranucci, M Aloi, L Della Volpe, F Viola, E Miele, S Cucchiara, R Iorio
BACKGROUND AND AIMS: Sclerosing cholangitis (SC) is a chronic cholestatic liver disease whose diagnosis is being increasingly recognized in childhood. Long-term course and prognosis of pediatric SC is poorly described. METHODS: We reviewed data of pediatric SC patients, followed in two referral centers during a period of up to 20 years. We aimed to evaluate long-term outcomes according to SC phenotype. RESULTS: Among 45 patients (median age: 10...
January 9, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Armin Mooranian, Rebecca Negrulj, Ryu Takechi, John Mamo, Hesham Al-Sallami, Hani Al-Salami
Probucol (PB) is an hypolipidaemic drug with potential antidiabetic effects. We showed recently using in vitro studies that when PB was incorporated with stabilising lipophilic bile acids and microencapsulated using the polymer sodium alginate, the microcapsules showed good stability but poor and irregular PB release. This suggests that PB microcapsules may exhibit better release profile and hence better absorption, if more hydrophilic bile acids were used, such as ursodeoxycholic acid (UDCA). Accordingly, this study aimed to produce PB-UDCA microcapsules and examine PB absorption and antidiabetic effects in our mouse-model of insulin-resistance and diabetes (fed high-fat diet; HFD)...
January 8, 2018: Drug Delivery and Translational Research
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