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Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： Robert Lam Joseph K Lim section of digestive diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis B virus Treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults

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World Journal of Transplantation 2024年第3期14卷 80-94页

作者： Sarpong Boateng Prince Ameyaw Solomon Gyabaah Yaw Adjepong Basile Njei Department of medicine Yale New Haven HealthBridgeport HospitalBridgeportCT 06610United States Department of Epidemiology and Biostatistics University of North TexasFort WorthTX 76107United States Department of medicine Komfo Anokye Teaching HospitalKumasi KS 1934Ghana yale university school of medicine New HavenCT 06520United States section of digestive diseases Yale University School of MedicineNew HavenCT 06520United States

BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney ***,information on how functional status,before and after transplant impacts post-transplant survival outcomes is *** To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States *** We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to *** primary outcome was *** the Karnofsky Performance Status,functional impairment was categorized as severe,moderate and *** were conducted using Kaplan-Meier curves and multivariable Cox *** The median age was 41 years,majority(53.4%)were *** impairment was present in 28.3%of *** median survival time was 906.6 *** median survival time was 1331 and 560 days for patients with normal and severe functional impairment *** with severe impairment had a 56%higher risk of mortality at one year[Hazard ratio(HR)=1.56;95%CI:1.23–1.98;P<0.001]and 58%at five years(HR=1.58;95%CI:1.24–2.00;P<0.001)compared to patients with no functional *** with worse functional status after transplant also had poor survival *** Pre-and post-transplant recipient functional status is an important prognostic indicator for short-and long-term intestinal transplant outcomes.

关键词： Intestinal transplantation Functional status Karnofsky performance status Post-transplant outcomes Survival analysis Transplant outcome

Cold snare polypectomy:A closer look at the efficacy and limitations for polyps 10-20 mm in size

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World Journal of Gastrointestinal Endoscopy 2024年第8期16卷 445-450页

作者： Louis A Chaptini Sarah Jalloul Karam Karam Department of medicine Digestive DiseasesYale School of MedicineNew HavenCT 06510United States Department of medicine GastroenterologyUniversity of BalamandBalamand 100Lebanon

Current guidelines recommend cold snare polypectomy for polyps less than 10 mm in ***,endoscopic mucosal resection is still the preferred technique for larger *** regarding cold snare polypectomy for larger polyps revolve around the difficulty in conducting en-bloc resection(resulting in piecemeal removal),and the potential for local residual polyp tissue and a high rate of *** the other hand,cold snare technique has the advantages of shortening procedure time,reducing delayed bleeding risks and lowering cost of *** ongoing and recent studies are focused on evaluating the risks and benefits of this technique for polyps larger than 10 mm,with the goal of providing clear guidelines in the near *** aim of this editorial is to provide our readers with an overview regarding this subject and the latest developments surrounding it.

关键词： Colon polyp Polypectomy Cold snare polypectomy Hot snare polypectomy Endoscopic mucosal resection Sessile serrated lesion Adenoma

The crosstalk between enteric nervous system and immune system in intestinal development,homeostasis and diseases

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Science China(Life Sciences) 2024年第1期67卷 41-50页

作者： Xindi Wang Chenbo Ding Hua-Bing Li Shanghai Institute of Immunology State Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong university school of medicine-yale Institute for Immune Metabolism Shanghai Jiao Tong University School of MedicineShanghai 200025China

The gut is the largest digestive and absorptive organ,which is essential for induction of mucosal and systemic immune responses,and maintenance of metabolic-immune *** intestinal components contain the epithelium,stromal cells,immune cells,and enteric nervous system(ENS),as well as the outers,such as gut microbiota,metabolites,and *** dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions,even colon diseases including dysplasia,inflammation and *** recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal(GI)*** crosstalk between ENS and immune cells,mainly macrophages,T cells,and innate lymphoid cells(ILCs),has been found to exert important regulatory roles in intestinal tissue programming,homeostasis,function,and *** this review,we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression,to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

关键词： enteric nervous system macrophages T cells innate lymphoid cells neuro-immune interactions

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of digestive diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1374-1383页

作者： Laura Sahyoun Kay Chen Cynthia Tsay George Chen Petr Protiva Department of Gastroenterology and Hepatology Weill Cornell MedicineNew YorkNY 10065United States Gastroenterology section Jennifer Moreno VA San Diego Healthcare SystemSan DiegoCA 92161United States Division of Gastroenterology Department of MedicineUniversity of California San DiegoLa JollaCA 92093United States Department of Gastroenterology and Hepatology John Hopkins HospitalBaltimoreMD 21287United States Department of digestive diseases Yale New Haven HospitalNew HavenCT 06520United States Department of Gastroenterology VA Connecticut Health Care SystemWest HavenCT 06516United States

BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival ***,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer *** from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to ***-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban *** was calculated with Cox proportional hazards models for death in the 5-year period following *** Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma *** analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

关键词： Biliary tract cancers Survival Outcomes research Socioeconomic factors Healthcare disparities

Hydroxycut hepatotoxicity:A case series and review of liver toxicity from herbal weight loss supplements

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World Journal of Gastroenterology 2008年第45期14卷 6999-7004页

作者： Lily Dara Jennifer Hewett Joseph Kartaik Lim Department of medicine Griffin Hospital section of digestive diseases Yale University School of Medicine

Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demon-strated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.

关键词： Hydroxycut Dietary supplements Liver Liver failure Toxicity Weight loss medicine Hepatitis

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第37期22卷 8294-8303页

作者： Carrie R Wong Mindie H Nguyen Joseph K Lim Department of Internal medicine Yale University School of Medicine Division of Gastroenterology and Hepatology Stanford University School of Medicine yale Liver Center Section of Digestive Diseases Yale University School of Medicine

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.

关键词： Fatty liver Nonalcoholic steatohepatitis Hepatocellular carcinoma Liver cirrhosis Liver cancer

Assessing the Effectiveness of Strategies in US Birth Cohort Screening for Hepatitis C Infection

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 25-41页

作者： Cynthia J.Tsay Joseph K.Lim Department of Internal medicine Yale University School of MedicineNew HavenCTUSA yale Liver Center Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA

Chronic hepatitis C infection in the USA is a highly morbid condition and current guidelines recommend one-time screening among the birth cohort(1945-1965).Understand-ing strategies to optimize screening can help inform future hepatitis C virus(HCV)screening guidelines.A focused literature search was performed using PubMed and manual abstract review from major hepatology conferences over the past 2 *** search strategy involved using Medical Subject Headings terms for hepatitis C,screening,birth cohort,baby boomers,and *** review was limited to data from the USA.A total of 327 articles were identified and 36 abstracts were included,with studies published between *** including clinician education,electronic medical record alerts,reflex HCV RNA testing,point-of-care testing,multisite(outpatient,inpatient,emergency department,endoscopy suite)initiatives,direct patient solicitation,and utilization of non-physician providers have increased HCV screening ***,broad imple-mentation remains less than *** include lack of patient acceptance to screening and engagement in the HCV care *** Veterans Affairs Healthcare System has achieved higher birth cohort screening rates through an integrated approach requiring high-level engagement by leadership and institutional *** strategies for increasing birth cohort screening have been successful,but overall rates of HCV screening remain *** strat-egies can inform public health efforts to implement emerging national recommendations for expansion of HCV screening to all *** age 18 or older.

关键词： Hepatitis C Epidemiology HCV antibody Screening Birth cohort Baby boomers Care cascade Electronic medical records