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Update on Sphincter of Oddi Dysfunction: A Review

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 515-521页

作者： Jaimy Villavicencio Kim george Y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Sphincter of Oddi dysfunction(SOD)encompasses a spectrum of clinical syndromes that are not fully understood,and various diagnostic and therapeutic methods have had varying results depending on the type of *** review explored various mechanisms that might play a role in SOD and methods of diagnosis and *** is important to rule out other causes of abdominal pain with laboratory testing,imaging studies,and endoscopic *** that affect sphincter motility should be identified as *** is the gold standard for diagnosis but it is not always *** example,patients with type I SOD may have symptomatic improvement with sphincterotomy without need for a diagnostic *** scintigraphy and fatty meal sonography may also have diagnostic *** is not always effective for symptomatic improvement in type II and III *** therapies with calcium channel blockers and botulinum toxin have been studied and might be considered as options after discussing the risks and benefits with the patients.

关键词： Sphincter of Oddi Sphincter of Oddi dysfunction Common bile duct Manometry Sphincterotomy

Primary Non-HFE Hemochromatosis:A Review

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 925-931页

作者： Alla Turshudzhyan David C.wu george Y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Iron homeostasis is a complex process in which iron uptake and use are tightly *** Type 1 or HFE hemochromatosis results from homozygous mutations in the gene that encodes human homeostatic iron regulator(known as human factors engineering,HFE)protein,a regulator of hepcidin,and makes up approximately 90%of all hemochromatosis ***,four types of hemochromatosis do not involve the HFE *** are non-HFE hemochromatosis type 2A(HFE2,encoding HJV),type 2B(HAMP,encoding hepcidin),type 3(TFR2,encoding transferring receptor-2),and types 4A and B(SLC40A1,encoding *** hemochromatosis is extremely *** allele frequencies have been estimated to be 74/100,000 for type 2A,20/100,000 for type 2B,30/100,000 for type 3,and 90/100,000 for type 4 *** guidelines recommend that the diagnosis be made by ruling out HFE mutations,history,physical examination,laboratory values(ferritin and transferrin saturation),magnetic resonance or other imaging,and liver biopsy if *** less common,non-HFE hemochromatosis can cause iron overload as severe as the HFE *** most cases,treatment involves phlebotomy and is successful if started before irreversible damage *** diagnosis and treatment are important because it prevents chronic liver *** review updates the mutations and their pathogenetic consequences,the clinical picture,diagnostic guidelines,and treatment of hemochromatosis.

关键词： Non-HFE Hemochromatosis Cirrhosis Iron homeostasis

Seronegative Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2023年第2期11卷 459-465,F0003页

作者： Sriya A.Bhumi george Y.wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Autoimmune hepatitis(AIH)is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 *** is characterized by the presence of ***,an average of 10% of AIH cases have AIH symptoms and pathology but lack autoimmune *** such seronegative AIH(snAIH)cases,there is currently no established diagnostic algorithm for *** improper or delayed diagnosis of snAIH can lead to no or inappropriate treatment that results in progression to fulminant hepatitis or *** review aims to review the current literature and to present an update of seronegative autoimmune hepatitis,including its pathophysiology,clinical presentation,methods of diagnosis,and treatment in order to increase awareness and emphasize the necessity for timely management.

关键词： Seronegative autoimmune hepatitis Autoantibody negative Autoimmune hepatitis Cryptogenic hepatitis

Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Review

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 531-542页

作者： Teresa Da Cunha Haleh Vaziri george Y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Primary sclerosing cholangitis is a disease affecting around 0.006–0.016%of the *** these,around 75%have concomitant inflammatory bowel disease(IBD)according to the most recent epidemiological *** theories have been proposed regarding the pathogenesis of primary sclerosing cholangitis(PSC).These include changes in the function of cholangiocytes,effects of the gut microbiome,association with specific human leukocyte antigen haplotypes and dysregulation of the immune ***,these do not explain the observed association with ***,there are considerable differences in the frequency and outcomes between patients with PSC and ulcerative colitis compared with PSC and Crohn’s *** aim of this review is to appraise the most recent studies that have contributed to the epidemiology,advances in the pathophysiology,and characterization of important clinical aspects of the association of PSC and IBD.

关键词： Primary sclerosing cholangitis Cholangitis Inflammatory bowel disease Ulcerative colitis Crohn’s disease

Immunotherapy-induced Hepatotoxicity:A Review

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1194-1204页

作者： Teresa Da Cunha george Y.wu Haleh Vaziri Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Immune checkpoint inhibitors(ICIs)suppress the func-tion of immune checkpoints,which are involved in down-regulating immune *** lead to an increased activation of the function of T cells,increased release of cytokines,and decreased activity of regulatory T *** allows for a more significant and less regulated im-mune response and subsequent enhanced cytotoxic activity against cancer cells.A number of cancers are now being treated with these agents and this increased use has re-sulted in more reports of *** almost every organ can be affected,the skin,gastrointestinal tract,liver,and endocrine glands are most commonly *** is neces-sary that gastroenterologists and hepatologists familiarize themselves with diagnostic steps and management plan in patients with these undesirable *** assessing for possible ICIs induced hepatotoxicity,it is of utmost im-portance to use a formal scoring system such as the Rous-sel Uclaf causality assessment method(RUCAM)to assess for risk factors,alternative causes,and response to cessa-tion and re-exposure of a given *** this review is based on studies with and without RUCAM,the conclusions were carefully established mainly from studies that used *** aim of this review is to provide information on the epidemiology,risk factors,clinical presentation,di-agnostic tools,and management plan based on the most recent studies of immunotherapy-induced hepatotoxicity.

关键词： Immune checkpoint inhibitors Immunotherapy Hepatitis Liver injury.

Statin-induced Liver Injury Patterns: A Clinical Review

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 543-552页

作者： Leon D.Averbukh Alla Turshudzhyan David C.wu george Y.wu Department of Medicine Division of Gastroenterology-HepatologyAllegheny Health NetworkPittsburghPAUSA Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Since their introduction in 1987,hydroxymethyl glutaryl coenzyme A reductase(HMG-CoA)inhibitors,more commonly known as statins,have become some of the most widely prescribed medications in the *** generally considered to be safe and well tolerated,statins have been associated with several side effects including mild liver dysfunction manifested by increases in ***,statins have been noted to induce more serious hepatic injury,including liver injury with autoimmune *** literature supports statin induced liver injury presenting in either hepatocellular or cholestatic patterns,though with the former being the prevailing pattern of ***,severe liver injury is uncommon with statin use and is generally reversible without any intervention other than offending statin *** evaluating cases of suspected statininduced liver injury,a complete medical history,laboratory tests including a complete metabolic panel,autoimmune markers,and viral panel,as well as hepatic imaging,are crucial for a complete causality analysis with validated tools such as Roussel Uclaf Causality Assessment *** aim of this review is to review the current evidence for statininduced liver injury and cholestasis.

关键词： Drug-induced liver injury Statin Cholestatic liver injury Hepatocellular liver injury Cholestasis Autoimmune hepatitis

Targeted Mitochondrial Delivery to Hepatocytes:A Review

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 321-328页

作者： Brent D.Heineman Xiaocong Liu george Y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Defects in mitochondria are responsible for various genetic and acquired *** transplantation,a method that involves introduction of healthy donor mitochondria into cells with dysfunctional mitochondria,could offer a novel approach to treat such *** studies have demonstrated the therapeutic benefit of mitochondrial transplantation and targeted delivery in vivo and in vitro within hepatocytes and the *** review discusses the issues regarding isolation and delivery of mitochondria to hepatocytes and the liver,and examines the existing literature in order to elucidate the utility and practicality of mito-chondrial transplantation in the treatment of liver *** reviewed demonstrate that mitochondrial uptake could specifically target hepatocytes,address the challenge of non-specific localization of donor mitochondria,and provide evidence of changes in liver function following injection of mitochondria into mouse and rat disease *** potential benefits and advantages of mitochondrial trans-plantation are evident,more research is needed to determine the practicality of mitochondrial transplantation for the treatment of genetic and acquired liver diseases.

关键词： Mitochondria Hepatocytes Transplantation Liver In vitro tech-niques

Primary Hepatic Extra-gastrointestinal Stromal Tumors:Molecular Pathogenesis,Immunohistopathology,and Treatment

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 942-948页

作者： Erica C.Becker Gonca Ozcan george Y.wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal *** originate from the interstitial cells of Cajal and are usually found in extrahepatic gastrointestinal ***,a small subset are derived from the liver and are known as primary hepatic gastrointestinal stromal tumors(PHGIST).They have a poor prognosis and are historically difficult to *** objective was to review and update the latest evidence-based knowledge concerning PHGIST,with a focus on epidemiology,etiology,pathophysiology,clinical presentation,histopathology,and *** tumors are usually found incidentally,occur sporadically,and are associated with mutations of KIT and PDGFRA *** is a diagnosis of exclusion,as it has the same molecular,immunochemistry and histological appearance as gastrointestinal stromal tumors(GIST).Thus,imaging,such as positron emission tomography-computed tomography(PET-CT)must be used to rule out metastatic GIST before a diagnosis can be ***,with mutation analysis and pharmacological advances,tyrosine kinase inhibitors are typically pursued with or without surgical *** potential treatments include transcatheter arterial chemoembolization and tumor ***,these are typically considered palliative *** there are only a limited number of publications regarding PHGIST,data concerning morbidity and mortality are not yet *** can help develop screening guidelines and evaluating resistance to treatment.

关键词： Primary hepatic gastrointestinal stromal tumor Gastrointestinal tumor Extra-gastrointestinal stromal tumor Primary gastrointestinal stromal tumor of the liver

Impact of Helicobacter pylori Infection on the Pathogenesis and Management of Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 670-674,F0003页

作者： Marianna G.Mavilia-Scranton george Y.wu Murali Dharan Department of Medicine Division of Gastroenterology and HepatologyUniversity of ConnecticutFarmington CTUSA

Helicobacter pylori(***)infection is widely prevalent *** infection has been reported to be a risk factor for the development of insulin resistance,nonalco-holic fatty liver disease(NAFLD),nonalcoholic steatohepatitis(NASH),liver fibrosis,and *** treatment for NAFLD,other than weight loss is limited,the treatment for *** infection is well *** is important to determine whether screening and treatment for *** infection should be considered in patients with no gastrointestinal *** aim of this mini-review is to evaluate the association be-tween *** infection and NAFLD including epidemiology,pathogenesis,and the evidence for *** infection as a modifiable risk factor for preventing or treating NAFLD.

关键词： Helicobacter pylori Hepatic fibrosis Hepatic steatosis Nonalco-holic fatty liver disease Nonalcoholic steatohepatitis