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Osteosarcopenia in autoimmune cholestatic liver diseases:Causes,management,and challenges

World Journal of Gastroenterology 2022年第14期28卷 1430-1443页

作者： Nicola Pugliese Ivan Arcari Alessio Aghemo Andrea G Lania Ana Lleo Gherardo Mazziotti Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090MilanItaly Division of Internal Medicine and Hepatology Department of GastroenterologyIRCCS Humanitas Research HospitalRozzano 20089MIItaly Department of Endocrinology Diabetology and Medical Andrology UnitIRCCS Humanitas Research HospitalRozzano 20089MIItaly

Primary biliary cholangitis and primary sclerosing cholangitis(PSC)are the most common cholestatic liver diseases(CLD)in adults and are both characterized by an immune *** primary biliary cholangitis is a model autoimmune disease,with over 90%of patients presenting very specific autoantibodies against mitochondrial antigens,PSC is considered an immune mediated *** is the most common bone disease in CLD,resulting in frequent fractures and leading to significant ***,sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of *** mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be *** timely diagnosis,prevention,and management of osteosarcopenia are crucial to limit the consequences,there are no specific guidelines for management of osteoporosis and sarcopenia in patients with *** guidelines recommend screening for bone disease at the time of diagnosis of ***,the optimal monitoring strategies and treatments have not been defined yet and vary among *** herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD,and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.

关键词： cholestatic liver diseases Primary biliary cholangitis Primary sclerosing cholangitis Osteoporosis Sarcopenia

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Bile acid signaling through farnesoid X and TGR5 receptors in hepatobiliary and intestinal diseases

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Hepatobiliary & Pancreatic diseases International 2015年第1期14卷 18-33页

作者： Bojan Stanimirov Karmen Stankov Momir Mikov Department of Pharmacology Toxicology and Clinical Pharmacology Faculty of Medicine University of Novi Sad Clinical Centre of Vojvodina Faculty of Medicine University of Novi Sad School of Pharmacy Curtin University

BACKGROUND： The well-known functions of bile acids（BAs） are the emulsification and absorption of lipophilic xenobiotics. However, the emerging evidences in the past decade showed that BAs act as signaling molecules that not only autoregulate their own metabolism and enterohepatic recirculation, but also as important regulators of integrative metabolism by activating nuclear and membrane-bound G protein-coupled receptors. The present review was to get insight into the role of maintenance of BA homeostasis and BA signaling pathways in development and management of hepatobiliary and intestinal *** SOURCES： Detailed and comprehensive search of PubM ed and Scopus databases was carried out for original and review ***： Disturbances in BA homeostasis contribute to the development of several hepatobiliary and intestinal disorders, such as non-alcoholic fatty liver disease, liver cirrhosis, cholesterol gallstone disease, intestinal diseases and both hepatocellular and colorectal ***： Further efforts made in order to advance the understanding of sophisticated BA signaling network may be promising in developing novel therapeutic strategies related not only to hepatobiliary and gastrointestinal but also systemic diseases.

关键词： bile acid metabolism non-alcoholic fatty liver disease cholestatic liver diseases gallstone disease intestinal disease hepatocellular carcinoma

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Antihepatic Fibrosis Drugs in Clinical Trials

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Journal of Clinical and Translational Hepatology 2020年第3期8卷 304-312页

作者： Yue-Cheng Guo Lun-Gen Lu Shanghai Key Laboratory of Pancreatic diseases Shanghai Jiao Tong University School of MedicineShanghaiChina Department of GastroenterologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

liver fibrosis is not an independent *** refers to the abnormal proliferation of connective tissues in the liver caused by various pathogenic *** far,liver fibrosis has been considered to be associated with a set of factors,such as viral infection,alcohol abuse,non-alcoholic fatty liver disease,and autoimmune hepatitis,as well as genetic *** date,clinical therapeutics for liver fibrosis still face challenges,as elimination of potential causes and conventional antifibrotic drugs cannot alleviate fibrosis in most ***,potential therapeutic targets of liver fibrosis,such as metabolism,inflammation,cell death and the extracellular matrix,have been explored through basic and clinical ***,it is extremely urgent to review the antihepatic fibrosis therapeutics for treatment of liver fibrosis in current clinical trials.

关键词： liver fibrosis Therapeutics Clinical trial cholestatic liver diseases Non-alcoholic steatohepatitis

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Primary sclerosing cholangitis in Turkish patients:characteristic features and prognosis

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Hepatobiliary & Pancreatic diseases International 2009年第3期8卷 312-315页

作者： Hilmi Ataseven Erkan Parlak lhami Yüksel mer Ba■ar brahim Ertu■rul Nurgül ■a■maz Burhan ■ahin Department of Gastroenterology Türkiye Yüksek htisas Hospital Department of Gastroenterology Di■kapl Yildirlm Beyazlt Education and Research Hospital

BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile *** study aimed to demonstrate the hepatic and extrahepatic characteristic findings and prognostic outcomes of Turkish patients with PSC. METHODS:The medical records of 35 consecutive patients with PSC from January 1988 to June 2007 were recorded *** the time of diagnosis,clinical features and laboratory data were collected. RESULTS:The mean age of the 35 patients was 41.69 years (range 15-80 years)at the time of diagnosis;14(40%)were female,and 21(60%)were *** mean duration of follow-up was 58.86 months(1-180 months).Twenty(57.1%) of the patients with PSC were asymptomatic and 22(62.9%) had inflammatory bowel *** the time of diagnosis, 20(57.1%)of the patients had both intra-and extra-hepatic ***-one(60%)of the patients,who had undergone ERCP for stent placement,had dominant bile duct stenosis. Cholangiocarcinoma was found in 2(5.7%)of the patients and cirrhosis was detected in 7(20%);5(14.3%)underwent liver *** median follow-up time after liver transplantation was 23 months and all are still *** (17.1%)patients died. CONCLUSIONS:PSC has a clinical course varied from advanced liver disease requiring liver transplantation within a short time to being asymptomatic for decades. The prognosis of Turkish patients with PSC is also disappointing as described in other studies.

关键词： primary sclerosing cholangitis cholestatic liver diseases biliary tree endoscopic retrograde cholangiopancreatography

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Bile acid metabolism and signaling in liver disease and therapy

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liver Research 2017年第1期1卷 3-9页

作者： John Y.L.Chiang Department of Integrative Medical Sciences College of MedicineNortheast Ohio Medical UniversityRootstownOHUSA

Bile acids play a critical role in the regulation of glucose,lipid,and energy metabolism through activation of the nuclear bile acid receptor farnesoid X receptor(FXR)and membrane G protein-coupled bile acid receptor-1(Gpbar-1,aka TGR5).Agonist activation of FXR and TGR5 improves insulin and glucose sensitivity and stimulates energy metabolism to prevent diabetes,obesity,and non-alcoholic fatty liver disease(NAFLD).Bile acids have both pro-and anti-inflammatory actions through FXR and TGR5 in the intestine and *** the intestine,bile acids activate FXR and TGR5 to stimulate fibroblast growth factor 15 and glucagon-like peptide-1 *** and TGR5 agonists may have therapeutic potential for treating liver-related metabolic diseases,such as diabetes and NAFLD.

关键词： Bile acid metabolism cholestatic liver diseases Metabolic diseases

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