Podcasts about udca

In this episode, Dr Gideon Hirschfield meets with patient advocate Jess Schnur to discuss challenges related to the diagnosis and management of primary biliary cholangitis (PBC) to provide actionable strategies for healthcare professionals to incorporate into patient care, including:Disease concerns and frequently asked questions from a patient perspectiveManaging symptomsTreatment options and supportive careImportance of awareness and educationPresenters:Gideon Hirschfield, MA, MB BChir, FRCP, PhDLily and Terry Horner Chair in Autoimmune Liver Disease ResearchProfessor, Division of Gastroenterology and HepatologyUniversity of TorontoDirector, The Autoimmune and Rare Liver Disease ProgrammeDirector, Francis Family Liver ClinicToronto General Hospital, University Health NetworkOntario, CanadaJess N. Schnur, BSN-RNNational PBC Patient AdvocateAmerican Liver FoundationDonation Support Services CoordinatorLifeline of OhioColumbus, OhioTo learn more, see the program Hear Me: Patient Perspectives on PBC

In this podcast, expert faculty, Dr Stuart Gordon and Dr Nancy Reau, use an illustrative patient case to explore the roles of ALP and other biochemical markers in PBC management, and explain what to expect from treatment. Topics covered include: How baseline ALP can affect ALP normalization after second-line treatment with elafibranor and seladelparPotential outcomes if ALP normalization cannot be achievedThe importance of managing fatigue, pruritus, and sleep disturbances independently of the biochemical responsePresenters:Stuart C. Gordon, MDProfessor of MedicineWayne State University School of MedicineDirector, Division of HepatologyHenry Ford HealthDetroit, MichiganNancy Reau, MDProfessor of MedicineRichard B. Capps Chair of HepatologyChief, Section of HepatologyAssociate Director, Solid Organ TransplantationRush University Medical CenterChicago, IllinoisTo learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management.  

In this podcast, expert faculty, Dr Stuart Gordon and Dr Nancy Reau discuss an illustrative patient case to demonstrate how they individualize primary biliary cholangitis (PBC) therapy for patients ​with cirrhosis. Topics covered include:AASLD guideline recommendations for second-line therapy for PBCConsiderations when using newer agents for second-line treatment of PBC in patients with cirrhosis: elafibranor and seladelparPresenters:Stuart C. Gordon, MD Professor of MedicineWayne State University School of MedicineDirector, Division of HepatologyHenry Ford HealthDetroit, MichiganNancy Reau, MD Professor of MedicineRichard B. Capps Chair of HepatologyChief, Section of HepatologyAssociate Director, Solid Organ TransplantationRush University Medical CenterChicago, IllinoisTo learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management.

In this podcast, Sonal Kumar, MD, MPH, meets with patient advocate Maria Morais to discuss actionable steps that healthcare providers can incorporate into the care of people with primary biliary cholangitis (PBC). Listen as they discuss:The chronic nature of PBCGoing beyond biochemical markers to assess and address symptoms such as fatigue and pruritusThe importance of referral to patient support groupsPresenters:Sonal Kumar, MD, MPHAssistant Professor of MedicineDirector, General Gastroenterology and HepatologyWeill Cornell Medical CollegeNew York, New YorkMaria G. Morais, RNVP Patient AdvocacyCanadian PBC SocietyToronto, CanadaTo learn more, see the program Hear Me: Patient Perspectives on PBC

In this episode, Christopher L. Bowlus, MD, discusses recent advances in the management of primary biliary cholangitis (PBC), including:Treatment goalsUse of PPAR agonists for the treatment of PBCClinical trial results for elafibranor (ELATIVE), seladelpar (RESPONSE), and bezafibrate (BEZURSO)Presenter:Christopher L. Bowlus, MDLena Valente Professor and ChiefDivision of Gastroenterology and HepatologyUniversity of California Davis School of MedicineSacramento, CaliforniaLink to full program: https://bit.ly/41tvSDuGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify.

In this episode, Christopher L. Bowlus, MD, discusses recent advances in the management of primary biliary cholangitis (PBC), including:Treatment goalsUse of PPAR agonists for the treatment of PBCClinical trial results for elafibranor (ELATIVE), seladelpar (RESPONSE), and bezafibrate (BEZURSO)Presenter:Christopher L. Bowlus, MDLena Valente Professor and ChiefDivision of Gastroenterology and HepatologyUniversity of California Davis School of MedicineSacramento, CaliforniaLink to full program: https://bit.ly/41tvSDuGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify.

Germán Anzola, rector de la Universidad de Ciencias Aplicadas y Ambientales (UDCA), habló en W Fin de Semana acerca de los objetivos del acuerdo por la preservación del medio ambiente.

Germán Anzola, rector de la Universidad de Ciencias Aplicadas y Ambientales (UDCA), habló en W Fin de Semana acerca de los objetivos del acuerdo por la preservación del medio ambiente.

Join John, Will and Paul for a conversation all about bile and the healing properties of Ursodeoxycholic acid (or UDCA... or Urso..). Hear about what's in bile, gall stones and other problems of the biliary system.

During the 2023 American Association for the Study of Liver Diseases conference, exciting and important results from many primary biliary cholangitis (PBC) clinical trials were reported, including 3 late-breaking studies on the PPAR-δ agonist seladelpar, the dual PPAR agonist elafibranor, and the combination of the FXR agonist obeticholic acid and a fibrate.In this episode, Kris V. Kowdley MD, FAASLD, FACP, FACG, discusses topline results from several of these studies and more, including: A combination of 3 studies—HEROES, COBALT, and COBALT EC—that evaluated the real-world effectiveness and safety of second-line therapy in PBC where OCA was added to the treatment regimen of people with PBC with an incomplete response to ursodeoxycholic acid Lessons learned from a long-term outcomes study of people with PBCResults from 2 phase II studies of obeticholic acid plus bezafibrate in people with PBC who did not respond to or were intolerant of ursodeoxycholic acidPresenter:Kris V. Kowdley MD, FAASLD, FACP, FACGProfessor, Elson S. Floyd College of MedicineWashington State UniversityDirector, Liver Institute NorthwestSeattle, Washington      Link to reviews of other PBC studies from AASLD 2023: https://bit.ly/3RvXXEI

During the 2023 American Association of the Study of Liver Diseases (AASLD) conference, exciting and important results from many primary biliary cholangitis (PBC) clinical trials were reported, including 3 late-breaking studies on the PPAR-delta agonist seladelpar, the dual PPAR agonist elafibranor, and the combination of the FXR agonist obeticholic acid and a fibrate.In this episode, Stuart C. Gordon, MD, FAASLD, discusses topline results from one of these late-breaking studies and more, including: A phase III study of an investigational PPAR-delta agonist (seladelpar) in people with PBC who had failed to respond to ursodeoxycholic acidA study that explored racial differences as they relate to the presentation and diagnosis of PBCPresenter: Stuart C. Gordon, MD, FAASLDDirector of HepatologyHenry Ford Health SystemProfessor of MedicineWayne State University School of MedicineDetroit, MichiganLink to commentary:https://bit.ly/3GzRMt2Link to reviews of other PBC studies from AASLD 2023:https://bit.ly/3RvXXEI

In this week's episode we are talking to Heidi and Liv. Heidi and Liv are both 3rd year vet students at the University Of Liverpool, with unique alternative entry routes. Heidi worked on a dairy farm. Liv qualified as an RVN and worked in a small animal clinic. The shared experience of parent loss has strengthened their friendship, and together with Tobias they founded the Bereaved Vet Students Group (@bereavedvetstudentsgroup) . They are on a mission to improve bereavement support, and to create a safer space within the profession for anyone coping with grief and loss.  Heidi found strength in CrossFit, and if not in the gym she can be found with her pet goats. She discusses the difficulties of being an autistic vet student, and the importance of self-acceptance to show up as your true (weird) self. Liv continues to work as an RVN around her studies and is an avid cinema goer after a long day at university. She discusses many things… including hiding in the toilet!   Heidi: Instagram - @CrossFitVet Liv:  Instagram - @_livfreeman_  Twitter/ X - @TheRVNVet    We are thrilled to be joined by the lovely Gemma for our clinical chat today. Scott and Gemma continue their conversation about the treatment of liver disease, with a focus on steroids and UDCA. A massive thank you to our incredible friends at Protexin for supporting this conversation: www.protexinvet.com www.vtx-cpd.com  

Chronic inflammation is the root cause of so many diseases! This is why Dr. Jockers has brought in an amazingly well-informed guest on the subject, Dr. Jay Davidson, as part of his Chronic Inflammation Summit.   Recognized as a leading foundational medicine expert, and known as “The Lyme Guy” for his expertise in natural protocols for Lyme disease and other related chronic illnesses, Dr. Jay Davidson (like Dr. Jockers) is all about seeking holistic solutions for those struggling with chronic illness.   Together they're discussing liver issues. What is the function of the liver? How do we detox? What is bile? Understanding the blood-bile barrier and how ‘leaky gut' can cause itchiness and skin rashes is also covered, as are the anti-inflammatory bile acids, UDCA, and TUDCA.    This is honestly one episode of Functional Nutrition that you are absolutely not going to want to miss, as we learn about bio-active carbons and how best to give your liver the love that it needs, from understanding the science to the supplements and herbs we should be putting in our body to support it.    Please take a minute to share this episode if you find it to be of value! Please join us.   In This Episode:   Introduction to Dr. Jay Davidson What is the function of the liver? Are we getting optimal support for the liver? What is bile?  Why am I lacking stomach acid? What are UDCA and TUDCA? Anti-inflammatory bile acids What does having a lack of bile production cause? Why do we have backed-up bile ducts? What are the main symptoms of poor bile flow? What labs can you look at for liver and bile function? Give your liver some love! How to create balance between Phase One and Phase Two Favorite liver cleansing herbs and supplements What herbs and bitters should you add to your diet? Coffee enemas! Understanding the gallstone flush Why we need to be flushing our gall system Are castor oil packs a good idea? What is the optimal dosage of TUDCA? What if you're having difficulty digesting fats? Dr. Davidson's kidney liver support products What are bio-active carbons?   "Just move forward" (final words of inspiration) This podcast is sponsored by ShopC60.com. C60 is a powerful, Nobel Prize-winning antioxidant, that helps to optimize mitochondrial function, fights inflammation, and neutralizes toxic free radicals!   I'm a big fan of using C60 in conjunction with your keto and intermittent fasting lifestyle to support your immune system, help your body detox, and increase energy and mental clarity.    My favorite C60 products for Keto & IF lifestyles include C60 Purple Power in Organic MCT Coconut Oil (can add this to your coffee) and their delicious Sugar-Free C60 Gummies (made with allulose and monk fruit)!   If you are over the age of 40, and you'd like to kick fatigue and brain fog to the curb this year, visit shopc60.com and use the coupon code “JOCKERS” for 15% OFF  and start taking back control over your health today!   Today's episode is proudly sponsored by Paleovalley and its Essential C Complex. Not only does this immunity-boosting product have the three most potent sources of Vitamin C on the planet, but it also gives you 750% of the daily recommended dose – exactly the amount your immune system needs to stay in top shape.  Hurry and grab yours from Paleovalley.com       “I love this organ (the liver). It is the lifeline of the body. It is the detox system, essentially, of our body." - Dr. Davidson   Subscribe to the podcast on: Apple Podcast Stitcher Spotify PodBean  TuneIn Radio   Resources: Shop Carbon 60 - Use the coupon code "JOCKERS" for 15% OFF your first order in all their products! Essential C Complex  Connect with Dr. Davidson: Website - https://www.drjaydavidson.com/   Connect with Dr. Jockers: Instagram – https://www.instagram.com/drjockers/ Facebook – https://www.facebook.com/DrDavidJockers YouTube – https://www.youtube.com/user/djockers Website – https://drjockers.com/ If you are interested in being a guest on the show, we would love to hear from you! Please contact us here! - https://drjockers.com/join-us-dr-jockers-functional-nutrition-podcast/

Petra Lynen plaudert mit Ansgar Lohse über einen sensationellen Zufallsbefund, die beste Nebenwirkung von Ursodeoxycholsäure und warum leberkranke Patienten nicht unbedingt zu den vulnerablen Gruppen gehören. Alle Informationen und Links zur Folge finden Sie in den Shownotes und unter dgvs.de/podcast Wenn Ihnen die Folge gefallen hat, abonnieren Sie uns oder lassen Sie uns eine Bewertung da. Haben Sie Feedback oder Fragen zur Folge oder möchten Sie ein Thema vorschlagen, dann schreiben Sie uns an podcast@dgvs.de.

近日，英国剑桥大学的研究人员在Nature期刊发表了一篇研究论文。该研究显示“一种治疗肝病的药物熊去氧胆酸（UDCA）可以关闭 ACE2 受体，该药物可以用于预防新冠感染。”

Intrahepatic Cholestasis of Pregnancy (ICP).Amel and Dr Wonderly discuss the signs, symptoms, and management of ICP. A reminder for alcohol use disorder screening.Introduction: Screening for alcohol use disorder. Written by Hector Arreaza, MD. Reviewed by Jacqueline Uy, MD. Today is December 3, 2021.Substance misuse occurs in about 20% of patients seen in primary care settings. For example, alcohol-related disorders are present in up to 26% of general clinic patients, “a prevalence rate similar to those for such other chronic diseases as hypertension and diabetes”[1]. The USPSTF recommends screening for unhealthy alcohol use in adults 18 years or older, including pregnant women, and provide those engaged in risky drinking with brief behavioral counseling to reduce alcohol use (this is a Grade B recommendation). This brief introduction is to encourage everyone to screen adults for alcohol use disorder. Let's start with the basics.  It is important to know the size of a standard drink so you can counsel your patients appropriately. According to the CDC, a standard drink is equal to 14 grams (0.6 ounces) of pure alcohol. Generally, this amount of pure alcohol is found in:12 ounces of beer (5% alcohol content).8 ounces of malt liquor (7% alcohol content).5 ounces of wine (12% alcohol content).1.5 ounces or a “shot” of 80-proof (40% alcohol content) distilled spirits or liquor (such as gin, rum, vodka, whiskey).Moderate alcohol drinking means 2 drinks or less in a day for men and 1 drink or less in a day for women. Binge drinking means drinking enough to bring your blood alcohol concentration (BAC) level to 0.08% or more. This may be different in each patient, as humans metabolize alcohol differently, but usually it corresponds to 5 or more drinks on a single occasion for men or 4 or more drinks on a single occasion for women, generally within about 2 hours[2]. A good approach to screen for alcohol use disorder is by asking: “Do you sometimes drink alcoholic beverages?”, and then the single screening question, “How many times in the past year have you had 5 or more drinks (men) OR 4 or more drinks (women) in a day?”[3]  The screening is considered positive if the patient answers one or more times a year. If positive, then you may continue your assessment with another tool such as AUDIT. This can be a topic for a whole episode.  For now, we just want to remind you to screen your patients for alcohol use because the prevalence is very high and we as primary care physicians can make a big difference in the prevention and treatment of alcohol misuse in our communities.  This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. Intrahepatic Cholestasis of Pregnancy (ICP). Written by Amel Tabet, MS3, American university of the Caribbean. Discussion with Sally Wonderly, MD; and Hector Arreaza, MD.What is Intrahepatic Cholestasis of Pregnancy and why does it matter?As its name implies, Intrahepatic Cholestasis of Pregnancy (ICP) is a multifactorial liver dysfunction in some pregnant women that occurs during their either second or third trimester of pregnancy and resolves spontaneously after parturition. It is defined by the presence of pruritus -- previously called pruritus gravidarum or recurrent jaundice of pregnancy-- and abnormally elevated serum bile acid levels and mildly increased hepatic aminotransferase levels, in the absence of diseases that may yield similar laboratory findings and symptoms. Key symptoms are pruritus, high bile acid and high transaminases. How common is ICP?In the US incidence ranges from 0.32 percent to 5.6 percent, depending on the area. The Los Angeles area has a high incidence compared to other areas in the US. The highest rates in Europe are in Scandinavia. It is very frequent in Chile (South America). The indigenous people known as Araucanos have the highest incidence worldwide at 27.6 percent.PathogenesisThe pathogenesis of ICP remains unclear. It is mainly attributed to changes in various sex steroid levels but more recent research points towards an etiology that relates to various mutations in the many genes involved in the control of the hepatocellular transport systems such as the ABCB4 gene, which encodes multidrug resistance protein 3 (MDR3) linked to progressive familial intrahepatic cholestasis, errors of the ABCB11 gene that encodes for the bile salt export pump, and more recently on FXR/NR1H4 and PXR/NR1I2 genes that encode for proteins that critically regulate bile acid synthesis and transport, and the transcription of ABCB11 in humans and the role of epigenetics influence by means of methylation of these genes. Dangers for mother: Beside the discomfort of pruritus, ICP is transient and of little maternal risk generally. The mother may be uncomfortable but it's not fatal. Danger to fetus: The elevated bile acids enter the fetal circulation because it crosses the placenta. Bile acids cause major fetal and neonatal complications, such as abnormal intrapartum fetal heart rate and meconium-stained amniotic fluid that can lead to fetal distress and prematurity or intrauterine demise and to neonatal respiratory distress syndrome associated with bile acids entering the lungs. Who is at risk for ICP?Multifetal pregnancies.Genetics: There is also a significant genetic influence that leads to variability of incidence by population. In North America, cholestasis is infrequent with an overall incidence approximating 1 case in 500 to 1000 pregnancies. Whereas its rate is high in indigenous women from Chile and Bolivia and nears 5.6 % among Hispanic women in Los Angeles. In other countries, for example Sweden, China, and Israel, the incidence varies from 0.25 to 1.5 %.Diet and environment can also have an influence. Research has shown an association of ICP with environmental and dietary factors such as seasonal changes of mineral dietary components and with gut-derived endotoxins subsequent to increased gastrointestinal permeability. This complex nature-nurture interaction suggests that ICP is strongly modulated by epigenetic mechanisms.Liver disease: Women with preexisting liver disease are at risk. Other risks include in vitro fertilization, cholelithiasis, advanced maternal age, and Hepatitis C and fatty liver disease.  History of ICP is an important risk, because it also recurs during subsequent pregnancies in 60 to 70 % of patients. Signs and symptoms:The main clinical presentation is an often-generalized pruritus in late second or third trimester, that usually starts and predominates on the palms and soles and is worse at night. It could range from mild to intolerable pruritus that may precede laboratory findings by several weeks and evidenced by possible presence of scratch marks and excoriations on physical examination. Jaundice arises in 14 to 25 % of patients and it typically develops 1 to 4 weeks after the onset of itching. Other accompanying symptoms may also occur such as nausea, RUQ pain, steatorrhea, poor appetite and sleep deprivation. Other signs include dark urine, pale stools. Diagnosis:To establish a diagnosis, careful history taking, physical examination, and laboratory evaluation are performed. Thus, in the absence of any other liver disease, ICP is diagnosed by the presence of pruritus that is associated with elevated total serum bile acid levels, elevated aminotransferases (seldom exceed 250 U/L), hyperbilirubinemia (4 to 5 mg/dL) and elevated alkaline phosphatase. In severe cases that account for 20%, cholestasis manifests as bile acids levels > 40 micromol/L.Differential diagnosis include: Preeclamptic liver disease, which is ruled out if blood pressure elevation or proteinuria are absent and cholelithiasis and biliary obstruction are excluded by sonography. Moreover, because of mild transaminitis in case of ICP, acute viral hepatitis is an improbable diagnosis. Liver biopsy is generally not needed. Even though not necessary for diagnosis, liver biopsy for research purposes, showed occurrence of changes with presence of cholestasis with bile plugs in the hepatocytes and canaliculi of the centrilobular regions, without inflammation or necrosis. These changes were found to fade after delivery with recurrence in successive pregnancies or with estrogen-containing contraceptives.Management:Management focuses mainly on reducing maternal discomfort due to pruritus and prevention of more serious fetal outcomes and reduce the risks of prenatal morbidity and mortality. For patients that have persistent clinical findings consistent with ICP without any biochemical evidence of ICP, we only treat with antihistamines and topical emollients such as calamine lotion and we perform a weekly evaluation of maternal total serum bile acid (TSBA) level.  In symptomatic patients with positive biochemical evidence of ICP we treat with ursodeoxycholic acid (UDCA) 300 mg BID or TID until delivery. UDCA was found in clinical trials to relieve pruritus, lower bile acid and serum enzyme levels, and to reduce preterm birth, fetal distress, respiratory distress syndrome, and neonatal intensive care unit admission. Along with treatment, we continue the weekly evaluation of the TSBA level with a warranted earlier delivery if TSBA ≥100 micromol/L and the related high risk of stillbirth.  Thus, delivery management is mainly based on the highest TSBA level at any time during pregnancy. If TSBA level is

NAMIJENJENO ISKLJUČIVO ZDRAVSTVENIM DJELATNICIMA. PRISTUPOM PODCASTU POTVRĐUJETE DA STE ZDRAVSTVENI DJELATNIK.PREDAVAČ:Prof.dr.sc. NERMIN SALKIĆ, dr.med.specijalista interne medicinesubspecijalista gastroenterologvanredni profesor na Katedri za internu medicinuMedicinskog fakulteta Univerziteta u TuzliTuzla, BiHLINK NA TEČAJPristupom na CME aktivnost na Portalu CME.ba imate priliku da na kraju iste uradite završni test, te da dobijete akreditovani CME certifikat.Ursodeoksiholna kiselina (UDCA) je lijek koji ima višestruku primjenu u hepatologiji, a i u nekim stanjima u gastroenterologiji. Neizostavan je u tretmanu različitih holangiopatskih stanja poput primarne bilijarne ciroze, primarnog sklerozirajućeg holangitisa, kao i holestaze u trudnoći.UDCA se takođe sa uspjehom može primjenjivati kao adjuvantni tretman nekih drugih jetrenih bolesti, a svoju primjenu ima i u pacijenata sa holesteroloskim kamencima žučne kesice, gdje u pojedinih, dobro probranih pacijenata može prevenirati dalji rast kalkulusa, a manje kamence čak i otopiti.O svemu ovome, indikacijskom području, dozama i primjeni UDCA u različitim kliničkim entitetima pogledajte i poslušajte u ovom pažljivo pripremljenom revijalnom predavanju.Aktivnost je preporučena za specijaliste i specijalizante gastroenterologije, interne medicine, pedijatrije infektologije, porodične medicine, a primjerena je i za studente medicine i magistre farmacije. Ova CME aktivnost je besplatna za registrirane članove. Registracija je također, besplatna.----------Ukoliko želite postati partner portala CME.ba ili želite da se Vaš brand ili audio poruke pojave na našim podcastima, mollimo da se javite na email info@cme.ba. Više informacija za potencijalne partnere potražite na OVOM LINKU.Bosnalijek d.d. Prvo zdravlje.

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FDA 连续批准2个治疗胆管癌的靶向药 Lancet 细胞海绵-三叶因子3监测法筛查Barrett食管Nature 胃肠道也有独立的神经系统培米加替尼（Pemigatinib）约20%的肝内胆管癌患者存在成纤维细胞生长因子受体（FGFR）2融合基因突变，培米加替尼（Pemigatinib）是一种选择性FGFR抑制剂。2020年4月，FDA批准培米加替尼治疗复发性的FGFR2基因融合或重排的局部晚期胆管癌。《FIGHT-202研究：培米加替尼治疗晚期胆管癌的临床研究》Lancet Oncology，2020年5月 (1)这个多中心、非盲、单臂、2阶段研究纳入FGFR2融合或重排的晚期胆管癌患者、其他FGF/FGFR基因突变的患者、和没有FGF/FGFR基因突变的患者肱146人。所有入组患者均接受培米加替尼治疗直到疾病进展、不可接受的毒性、撤回同意或医生决定。中位随访17·8个月，FGFR2融合或重排患者中35·5%达到客观缓解（其中3例完全缓解，35人部分缓解）。高磷酸盐血症是最常见的不良事件，49%的患者在研究期间死亡，最常见的原因是疾病进展，与治疗无关。结论：培米加替尼在以前治疗过的发生FGFR2融合或重排的胆管癌患者中均有一定疗效。艾伏尼布（ivosidenib）基因组分析表明，胆管癌中有13%的患者存在IDH1基因突变，艾伏尼布（ivosidenib）是一种新型的小分子靶向异柠檬酸脱氢酶1（IDH1）抑制剂。艾伏尼布2018年被FDA批准用于急性髓细胞性白血病的一线治疗，2020年4月批准用于胆管癌靶向治疗药物。《ClarIDHy研究：针对胆管癌异柠檬酸脱氢酶1（IDH-1）突变的新型靶向疗法的3期临床研究》Lancet Oncology，2020年8月 (2)胆管癌是一种对化疗敏感的癌症。尽管吉西他滨联合顺铂的一线化疗是标准治疗方案，但二线治疗却效果有限。这项国际性、双盲、安慰剂对照的、随机的、3期临床试验中，招募了185例携带IDH-1突变的胆管癌患者，其中大部分患者原发性肝内胆管癌（90%～95%）伴远处转移（92%～93%），随机接受艾伏尼布或安慰剂治疗。中位随访6.9个月时，艾伏尼布组的中位无进展生存期优于安慰剂组（2.7个月 vs 1.4个月，P

FDA 连续批准2个治疗胆管癌的靶向药 Lancet 细胞海绵-三叶因子3监测法筛查Barrett食管Nature 胃肠道也有独立的神经系统培米加替尼（Pemigatinib）约20%的肝内胆管癌患者存在成纤维细胞生长因子受体（FGFR）2融合基因突变，培米加替尼（Pemigatinib）是一种选择性FGFR抑制剂。2020年4月，FDA批准培米加替尼治疗复发性的FGFR2基因融合或重排的局部晚期胆管癌。《FIGHT-202研究：培米加替尼治疗晚期胆管癌的临床研究》Lancet Oncology，2020年5月 (1)这个多中心、非盲、单臂、2阶段研究纳入FGFR2融合或重排的晚期胆管癌患者、其他FGF/FGFR基因突变的患者、和没有FGF/FGFR基因突变的患者肱146人。所有入组患者均接受培米加替尼治疗直到疾病进展、不可接受的毒性、撤回同意或医生决定。中位随访17·8个月，FGFR2融合或重排患者中35·5%达到客观缓解（其中3例完全缓解，35人部分缓解）。高磷酸盐血症是最常见的不良事件，49%的患者在研究期间死亡，最常见的原因是疾病进展，与治疗无关。结论：培米加替尼在以前治疗过的发生FGFR2融合或重排的胆管癌患者中均有一定疗效。艾伏尼布（ivosidenib）基因组分析表明，胆管癌中有13%的患者存在IDH1基因突变，艾伏尼布（ivosidenib）是一种新型的小分子靶向异柠檬酸脱氢酶1（IDH1）抑制剂。艾伏尼布2018年被FDA批准用于急性髓细胞性白血病的一线治疗，2020年4月批准用于胆管癌靶向治疗药物。《ClarIDHy研究：针对胆管癌异柠檬酸脱氢酶1（IDH-1）突变的新型靶向疗法的3期临床研究》Lancet Oncology，2020年8月 (2)胆管癌是一种对化疗敏感的癌症。尽管吉西他滨联合顺铂的一线化疗是标准治疗方案，但二线治疗却效果有限。这项国际性、双盲、安慰剂对照的、随机的、3期临床试验中，招募了185例携带IDH-1突变的胆管癌患者，其中大部分患者原发性肝内胆管癌（90%～95%）伴远处转移（92%～93%），随机接受艾伏尼布或安慰剂治疗。中位随访6.9个月时，艾伏尼布组的中位无进展生存期优于安慰剂组（2.7个月 vs 1.4个月，P

Ursodiol or ursodeoxycholic acid (UDCA) is a bile acid derivative of cholesterol. Since it can have antioxidant, anti-inflammatory and anti-apoptotic effects, it has mechanisms by which it could slow ALS progression. Here we discuss trials of UDCA in PALS, including the taurine-conjugated form (TUDCA). Some of these trials came out after our ALSUntangled review, and have changed our opinion about UDCA as an ALS treatment.

Ursodiol or ursodeoxycholic acid (UDCA) is a bile acid derivative of cholesterol. Since it can have antioxidant, anti-inflammatory and anti-apoptotic effects, it has mechanisms by which it could slow ALS progression. Here we discuss trials of UDCA in PALS, including the taurine-conjugated form (TUDCA). Some of these trials came out after our ALSUntangled review, and have changed our opinion about UDCA as an ALS treatment.

Planeta Sostenible estrena mesa de trabajo. Hoy se realiza desde los hogares de los invitados y conductores.En la mesa de trabajo se encuentran Oscar Luis Pyszczek, geólogo y profesor de la UDCA, Adriana Molano, fundadora del Centro Latinoamericano de Digital para el Desarrollo - Olas Digitales, orientado hacia la gestión de proyectos en materia de tecnologías con impacto social, económico, cultural y ambiental, Rocío Sarmiento, Abogada y comunicadora social de profesión y Master en Responsabilidad social corporativa de corazón, y Ángela María Gómez Comunicadora Social y especialista en SostenibilidadEn este programa hablamos del ODS 4 Educación de Calidad y los retos en este momentos de Pandemia; Qué nos depara el futuro ¿es un quiebre en la presencialidad?Retos y desafío que nos plantea la inclusión y la conectividad para profesores y estudiantes.Conduce Ángela Gómez

PSC Partners Seeking a Cure is pleased to present Living With PSC, a podcast moderated by Niall McKay. Each month, this podcast will explore the latest research and knowledge about PSC. From patient stories, to the latest research updates from PSC experts, to collaborations that are necessary to find better treatments and a cure, this podcast has it all! In the eighth episode of Living with PSC, Niall McKay discusses the influence of the medication Ursodiol (aka URSO and UDCA) on PSC, including the impact of combining it with antihistamines, with Dr. Heather Francis, PhD, associate professor at the Texas A & M College of Medicine and recipient of a PSC Partners research grant. Enjoy!

Marco Carbone talks to The Lancet Gastroenterology & Hepatology about predicting treatment response for patients with primary biliary cholangitis

Marco Carbone talks to The Lancet Gastroenterology & Hepatology about predicting treatment response for patients with primary biliary cholangitis

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P 

Gallensäuren stellen potente Signalmoleküle dar, die schon in geringen mikromolaren Konzentrationen, wie sie beim Menschen im Serum beobachtet werden, zentrale Leberzellfunktionen auf transkriptioneller und posttranskriptioneller Ebene beeinflussen. Die hydrophoben und potentiell toxischen Gallensäuren Lithocholsäure (LCA) und Chenodeoxycholsäure (CDCA) induzieren Apoptose und Cholestase, während hydrophile Gallensäuren hepatoprotektiv wirken können. Unter ihnen ist die antiapoptotisch und anticholestatisch wirksame Ursodeoxycholsäure (UDCA) von besonderer Bedeutung. UDCA stellt derzeit das einzige wirksame Therapeutikum bei chronischen cholestatischen Leberkrankheiten dar. Die vorliegende Arbeit untersuchte die Bedeutung intrazellulärer Signaltransduktionswege für die choleretischen, (anti-)cholestatischen und (anti-)apoptotischen Wirkungen physiologischer Gallensäuren in verschiedenen experimentellen Modellen. Hauptziel der Arbeit war die genauere Charakterisierung (i) der für den klinisch bedeutenden anticholestatischen Effekt des Taurinkonjugats der Ursodeoxycholsäure (TUDCA) verantwortlichen Signaltransduktionswege, und (ii) der zentralen Stellung von PI3-Kinasen in der intrazellulären Signalvermittlung der biologischen Effekte hydrophiler und hydrophober Gallensäuren. Im Modell der isoliert perfundierten Rattenleber untersuchten wir die anticholestatische und hepatoprotektive Wirkung der TUDCA in der intakten Leber unter Einsatz pharmakologischer Enzyminhibitoren. Als Leberfunktionsparameter dienten quantitativer Gallenfluß, Sekretion des Modellsubstrats der Konjugatexportpumpe Mrp2, GS-DNP, in die Galle und als Marker der Leberzellschädigung die hepatovenöse LDH-Freisetzung. Simultane Hemmung der cPKCa und der PKA, nicht aber Hemmung von cPKCa oder PKA allein antagonisierte bei Taurolithocholsäure (TLCA)-induzierter Cholestase die protektive Wirkung der TUDCA. Gallenfluß und GS-DNP-Sekretion waren unter gleichzeitiger Hemmung beider Signalwege signifikant reduziert, wohingegen die LDH-Freisetzung deutlich erhöht war. Die Ergebnisse zeigen, dass der posttranskriptionell vermittelte anticholestatische Effekt der TUDCA im etablierten Modell TLCA-induzierter Cholestase durch einen kooperativen cPKC- und PKA-abhängigen Signalweg vermittelt wird. Mitogenaktivierte Proteinkinasen Erk1/2- und p38-abhängige Signalwege hingegen, die als Vermittler von TUDCA-induzierter Cholerese unter nicht-cholestatischen Bedingungen beschrieben wurden, waren im untersuchten Modell ohne Bedeutung für die anticholestatische Wirkung der TUDCA. Mit Hilfe der neu etablierten Biotinylierung von Membranproteinen konnten wir in Ntcp-transfizierten humanen Hepatomzellen (HepG2-Ntcp) zeigen, dass TUDCA unter Cholestase die Insertion von MRP2 in die Hepatozytenmembran anregt. Dieser für die klinische Wirksamkeit der (T)UDCA potentiell bedeutende und im Tiermodell von uns vorbeschriebene Wirkmechanismus konnte damit erstmals in einem humanen Modell nachvollzogen werden. Ein weiterer in vitro Ansatz untersuchte die Phosphorylierung von aus HepG2-Ntcp immunopräzipitiertem MRP2 durch die als Gallensäureneffektoren diskutierten Proteinkinasen cPKCa, nPKCe und PKA. Alle drei Proteinkinasen phosphorylierten, durch den PKC/PKA-Inhibitor Staurosporin hemmbar, MRP2. Diese Phosphorylierung könnte, wie für die Gallensäurentransporter BSEP und NTCP bereits gezeigt, Einfluss auf Aktivität und Membraninsertion von MRP2 haben. Der funktionellen Bedeutung der PI3-Kinasen, welchen in den bisher entschlüsselten Signalwegen sowohl hydrophober/toxischer wie auch hydrophiler/protektiver Gallensäuren eine zentrale Rolle zugesprochen worden war („PI3-Kinasen-Paradoxon“), galten unsere in vitro Untersuchungen zur Aktivität der Isoformen der Klasse I PI3-Kinasen p110a, p110b und p110g nach Stimulation von primären Rattenhepatozyten mit TLCA, GCDCA, TCA und TUDCA in einem neu etablierten isoformspezifischen Kinaseassay. Dabei zeigte sich für jede Gallensäure ein für sie spezifisches Aktivierungsmuster unterschiedlicher PI3-Kinase-Isoformen. PI3-Kinase p110g wurde dabei spezifisch durch die cholestatisch und apoptotisch wirkenden Gallensäuren TLCA und GCDCA aktiviert. In HepG2-Ntcp-Zellen untersuchten wir daher die Bedeutung von p110g für Gallensäuren-induzierte Apoptose nach deren pharmakologischer Hemmung bzw. nach Transfektion mit siRNA gegen p110g. Die apoptotische Wirkung u.a. der Gallensäuren TLCA und GCDCA war unter beiden Methoden der p110g-Antagonisierung deutlich reduziert, wie sowohl in einem Caspase3/7-Assay als auch morphologisch evaluiert. Gallensäuren-unabhängige Apoptose, durch Etoposid bzw. TNFa ausgelöst, war p110g-unabhänig. Die Bedeutung der Aktivierung der PI3-Kinase-Isoform p110a durch TUDCA ist durch weitere experimentelle Untersuchungen zu klären. Die Erkenntnisse der vorliegenden Arbeit tragen zum Verständnis der komplexen Signalgebung im Rahmen cholestatischer Leberschädigung und der therapeutischen Wirkung der (T)UDCA bei und sind damit für die Entwicklung neuer Therapiestrategien bei cholestatischen Leberkrankheiten potentiell von Bedeutung.

Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKCa agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCa-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. Methods: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. Results: In livers treated with TLCA (10 mmol/l)+TUDCA (25 mmol/l), combined inhibition of cPKC by the cPKCselective inhibitor Go¨6976 (100 nmol/l) or the nonselective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p,0.05) and 48% (p,0.01), and secretion of the Mrp2/ Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p,0.05) and 41% (p,0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKCa, nPKCe, and PKA, respectively, in a staurosporine-sensitive manner. Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCa-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.

Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and has therefore been used for the dissolution of cholesterol gallstones. It remained unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. The activities of the rate-limiting enzymes of both, cholesterol and bile acid synthesis, have been studied in normal subjects during 8-14 mg/kg UDCA feeding. Moreover, lipoproteins and bile acids were measured. Before, during, and after 40 days of UDCA ingestion, 7-alpha-hydroxy-4-cholesten-3-one in serum and urinary excretion of mevalonic acid were determined. Ursodeoxycholic acid treatment seems to not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may attribute to homeostasis of cholesterol in the liver while preventing an excess of cholesterol.

Introduction: Ursodeoxycholic acid (UDCA) therapy attenuates the risk of biliary pain and complications in patients with symptomatic gallstones [1]. However, it is unknown whether UDCA therapy might improve also the gastrointestinal quality of life in patients with “asymptomatic” cholecystolithiasis. Methods: Therefore we studied the effect of UDCA treatment in 35 patients [ ♀ = 21; age 36 – 72, av. 56.6; ♂ = 14; age 29 – 78, av. 59,8 ] with “asymptomatic” gall-stones, using the „Gastrointestinal Quality of Life Index“ (GIQLI) as previously introduced by Eypasch et al. [2] The 36 questions of the GIQLI had to be answered on a 5-digit scale (0;1;2;3;4), so if added up a total score of 144 could be obtained. The questionnaire was answered before and after a four-week treatment with 250 mg UDCA per day, taken in the evening. Results: The patients scored 107.0 ± 15.9 (mean ± SD ) points from an attainable maximum of 136* prior UDCA treatment, which increased significantly ( p < 0,01 ) to 119.0 ± 12.5 points after UDCA application. Five patients already had a high GIQLI-score ( 120↑) before the treatment with UDCA, which is indicating, that the innocent gall-stone is not a myth. The change of the GIQLI-score between the two measurements ranged from – 6 to + 50 points. 8 patients with an initial GIQLI-score ≤ 100 gained significantly more points ( p < 0,01 ) ( 22.5 ± 16.6 ), than the 27 patient with an initial GIQLI-score >100 ( 8.67 ± 6.84 ). Conclusions: Our study shows that a “silent gall-stone” is not always as silent as expected, and that furthermore a treatment with low dose UDCA can improve the gastrointestinal quality of life in patients with “asymptomatic” cholecystolithiasis, particularly in patients with an initial GIQLI-score ≤ 100 points. References: [1] Tomida S. et al. Hepatology 1999; 30: 6-13 [2] British Journal of Surgery 1995; 82: 216-222

Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.

Background: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. Methods: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. Results: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 mumol/l, 0.9-1.8) than in group B (0.7 mumol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. Conclusions: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation. Copyright (C) 2003 S. Karger AG, Basel.