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The role of Direct-acting Antivirals in the Treatment of Children with Chronic Hepatitis C

Journal of Clinical and Translational Hepatology 2017年第1期5卷 59-66页

作者： Christine Hong Ting Yang eric r.yoo Aijaz Ahmed Division of Pediatric Gastroenterology Stanford University School of MedicineStanfordCAUSA Department of Medicine University of Illinois College of MedicineChicagoILUSA Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCAUSA

In the United States,chronic infection with the hepatitis C virus(HCV)affects an estimated 0.1-2%of the pediatric population,who are consequently at risk for major complications,including cirrhosis,hepatocellular carcinoma,and *** current standard of treatment for chronic hepatitis C(CHC)in children is pegylated-interferon-alpha(PEG-IFN)in combination with ***-IFN/ribavirin therapy is approved for children ages 3 and older;however,it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse *** CHC is usually indolent in children and adolescents,immediately treating and curbing the spread of HCV before adulthood is important,as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy,the latter representing the most common means of transmission for children in the United *** recent development of direct-acting antivirals has shown promising results in clinical trials for use in children and has dramatically increased the rates of sustained virological response in adults while improving side effect profiles as compared to interferonbased *** the usually indolent course of CHC in children,significant side effects of the currently-approved PEG-IFN/ribavirin therapy,and likely availability of all-oral interferon-free regimens for children within a few years,deferring treatment in clinically-stable children with CHC in anticipation of upcoming superior treatment modalities may be justified.

关键词： Hepatitis C virus Chronic hepatitis C Pediatric Children Anti-viral therapy

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Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2017年第47期23卷 8263-8276页

作者： Brandon J Perumpail Muhammad Ali Khan eric r yoo George Cholankeril Donghee Kim Aijaz Ahmed Department of Medicine College of MedicineDrexel University Division of Gastroenterology and Hepatology Health Science CenterUniversity of Tennessee Department of Medicine Santa Clara Valley Medical Center Division of Gastroenterology and Hepatology Stanford University School of Medicine

Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

关键词： Nonalcoholic fatty liver disease Hepatic steatosis Fatty liver Prevalence Incidence Fibrosis risk factor Epidemiology Outcomes Nonalcoholic steatohepatitis

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Use of direct-acting antiviral agents in hepatitis C virusinfected liver transplant candidates

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World Journal of Gastroenterology 2018年第3期24卷 315-322页

作者： Chiranjeevi Gadiparthi George Cholankeril Brandon J Perumpail eric r yoo Sanjaya K Satapathy Satheesh Nair Aijaz Ahmed Division of Gastroenterology and Hepatology University of Tennessee Health Sciences CenterMemphisTN 38104United States Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCA 94304United States Drexel University College of Medicine PhiladelphiaPA 19129United States Department of Medicine Santa Clara Valley Medical CenterSan JoseCA 95128United States

Since the advent of direct acting antiviral(DAA) agents, chronic hepatitis C virus(HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant(LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response(SVr) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

关键词： Hepatitis C virus Direct-acting antiviral therapy Liver transplantation Purgatory Model for End-stage liver disease Sustained virological response

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Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals

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Journal of Clinical and Translational Hepatology 2017年第2期5卷 130-133页

作者： eric r.yoo ryan B.Perumpail George Cholankeril Channa r.Jayasekera Aijaz Ahmed Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Center for Innovation in Global Health Stanford UniversityStanford CA USA

In the United States,the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years,but the results have been less than ***,patients with chronic hepatitis C (CHC) were treated with interferon-based regimens,which were associated with frequent adverse effects,suboptimal response rates,and long durations of treatment-of up to 48 *** from specialistphysicians,such as hepatologists and gastroenterologists,was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse ***,the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety,tolerability,lack of adverse effects,efficacy,and truncated duration of therapy-12 weeks or less-thereby making the need for close monitoring by specialist-physicians *** the recent approval of DAA agents by the Food and Drug Administration,the treatment model for CHC no longer relies on the limited number of specialist-physicians,which represented a major barrier to treatment access in the past,especially in underserved areas of the United *** propose and share our experiences in adapting a task-shifting treatment model,one that utilizes a relatively larger pool of non-specialist healthcare providers,such as nursing staff (medical assistants,vocational licensed nurses,registered nurses,etc.) and advanced practice providers (nurse practitioners and physician assistants),to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV *** recently,task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging *** on our experiences in implementing this model at our outreach clinics,the majority of HCV-infected patients treated with DAA agents can be easily monitored by

关键词： Task-shifting Treatment Access Underserved Under-resourced Hepatitis C virus HCV Direct acting antivirals DAAs

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Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents

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Journal of Clinical and Translational Hepatology 2017年第4期5卷 363-367页

作者： George Cholankeril Mairin Joseph-Talreja Brandon J.Perumpail Andy Liu eric r.yoo Aijaz Ahmed Aparna Goel Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCAUSA Department of Medicine Drexel University College of MedicinePhiladelphiaPAUSA Department of Medicine California Pacific Medical CenterSan FranciscoCAUSA Department of Medicine Santa Clara Valley Medical CenterSan JoseCAUSA

Chronic hepatitis C virus(HCV)infection remains the leading indication for liver transplantation(LT)in the United *** most patients with chronic HCV infection remain asymptomatic,up to one-third develop progressive liver disease resulting in *** is often the only curative treatment once significant hepatic decompensation ***,antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral *** new regimens are well tolerated,of short duration and highly effective,unlike the traditional treatment with pegylated-interferon and *** achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients,concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant *** one hand,HCV treatment may improve hepatic function and negate the need for LT in some,which is crucial given the scarcity of donor organs and mortality on the waiting list in certain *** the other hand,HCV treatment may result in lowering the priority for LT without improving quality of life,thereby delaying potentially curative LT *** review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

关键词： Hepatitis C virus Direct-acting antiviral therapy Liver transplantation

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Sofosbuvir Use in the Setting of End-stage renal Disease:A Single Center Experience

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 23-26页

作者： Avin Aggarwal eric r.yoo ryan B.Perumpail George Cholankeril radhika Kumari Tami J.Daugherty Alex S.Lapasaran Aijaz Ahmed Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCAUSA Department of Medicine University of Illinois College of MedicineChicagoILUSA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences CenterMemphisTNUSA Digestive Health Associates RenoNVUSA

Background and Aims:Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESrD) who are dialysisdependent form a unique group,in which safety,tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further ***:We performed a retrospective analysis of 14 patients with CHC and ESrD on dialysis who received 15 courses of SOF-based *** evaluated dose escalation to standard-dose SOF in this proof-of-principle ***:Sustained virological response (defined as undetectable viral load at 12 weeks,SVr-12) was achieved in 13 out of the 15 (86.7%) treatment *** (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential *** 13 out of 15 treatment courses,patients completed the designated treatment *** patient was treated twice and developed SVr-12 with the *** patient was lost to follow-up and counted as a *** discontinuations were not due to DAA-related adverse *** were no reports of severe adverse effects or drug ***:We treated CHC patients with ESrD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVr rates comparable to general population.

关键词： Hepatitis C End-stage renal disease Sofosbuvir Direct-acting antivirals

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Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 740-750页

作者： Phillip Gu Shishir Dube Norman Gellada So Yung Choi Susan Win yoo Jin Lee Shaohong Yang Talin Haritunians Gil Y Melmed eric A Vasiliauskas Niru Bonthala Gaurav Syal Andres J Yarur David Ziring Shervin rabizadeh Phillip Fleshner Cindy Kallman Suzanne Devkota Stephan r Targan Dalin Li Dermot PB McGovern Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Biostatistics Shared resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea Department of Medicine University of California at Los AngelesLos AngelesCA 90095United States Department of Medicine University of California at San DiegoSan DiegoCA 92093United States Department of Pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGrOUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POr)of Crohn’s disease(CD).However,its prognostic value is INTrODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory ***,surgery is not curative,and many patients develop post-operative recurrence(POr)of CD with a significant proportion eventually requiring additional *** advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POr,but each have potential ***,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after *** strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off ***,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting

关键词： Crohn’s disease Surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

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rising rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States

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Journal of Clinical and Translational Hepatology 2017年第3期5卷 193-196页

作者： Osama Siddique Mairin Joseph-Talreja eric r.yoo ryan B.Perumpail George Cholankeril Stephen A.Harrison Zobair M.Younossi robert J.Wong Aijaz Ahmed Department of Medicine Memorial Hospital of Rhode Island/Alpert Medical School of Brown University Providence RI USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA radcliffe Department of Medicine University of Oxford Oxford United Kingdom Department of Medicine Center for Liver DiseasesInova Fairfax HospitalFalls ChurchVAUSA Division of Gastroenterology and Hepatology Alameda Health SystemHighland HospitalOaklandCAUSA

Background and Aims:Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next *** aimed to study the trends in NASH-related LT among persons born between 1945 and 1965,the baby boomer (BB) ***:We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with *** stratified our study population into three birth cohorts:1) birth before 1945,2) birth between 1945 and 1965,and 3) birth after ***:The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB *** 2004 to 2015,the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth,60.6% in 2004 versus 83.2% in 2015 (p r transplant recipients with NASH,the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p report rising rates of waitlist registration and LT for the indication of *** importantly,the BB sub-cohort was mainly responsible for these alarming trends.

关键词： Baby boomers Liver transplantation Non-alcoholic steatohepatitis Waitlist

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Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher

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Journal of Clinical and Translational Hepatology 2016年第3期4卷 169-174页

作者： ryan B.Perumpail eric r.yoo George Cholankeril Lupe Hogan Melodie Deis Waldo C.Concepcion C.Andrew Bonham Zobair M.Younossi robert J.Wong Aijaz Ahmed Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA Division of Surgery Division of Abdominal Transplantation Stanford University School of Medicine Stanford CA USA Department of Medicine Center for Liver Diseases Inova Fairfax HospitalFalls Church VA USA Division of Gastroenterology and Hepatology Alameda Health System Highland Hospital CampusOakland CA USA

Background and Aims:Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.).We evaluated the association between recipient MELD score at the time of surgery and survival following ***:All *** LDLT recipients with MELDre evaluated using the 1995-2012 United Network for Organ Sharing *** following LDLTwas stratified into three MELD categories (MELDr methods and multivariate Cox proportional hazards ***:Overall,2,258 patients underwent *** to patients with MELDrall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs.80.3%,p =0.77) and MELD 20-24 (81.2% vs.80.3%,p =0.73).When compared to patients with MELDre was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (Hr:1.11,95% CI:0.85-1.45,p =0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (Hr:1.28,95%CI:0.91-1.81,p =0.16).Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELDrutilized in patients with MELD 20 and higher.

关键词： Living donors Liver transplantation Waitlist Model for End-Stage Liver Disease(MELD)

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Bioreactor design and validation for manufacturing strategies in tissue engineering

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Bio-Design and Manufacturing 2022年第1期5卷 43-63页

作者： Diana Lim eric S.renteria Drake S.Sime Young Min Ju Ji Hyun Kim Tracy Criswell Thomas D.Shupe Anthony Atala Frank C.Marini Metin N.Gurcan Shay Soker Joshua Hunsberger James J.yoo Wake Forest Institute for regenerative Medicine Wake Forest School of MedicineWinston-SalemNC 27157USA Center for Biomedical Informatics Wake Forest School of MedicineWinston-SalemNC 27157USA regenMed Development Organization(reMDO) Winston SalemNC 27106USA

The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or *** maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for ***,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in ***-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management *** present review provides a brief overview of bioreactor engineering *** addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.

关键词： Bioreactor Monitoring sensors and automation Manufacturing Tissue engineering regenerative medicine

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