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Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding Hepatitis C Treatment Access in the United States

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 16-22页

作者： Channa R.Jayasekera Rachel Beckerman Nathaniel Smith Ryan B.Perumpail Robert J.Wong zobair m.younossi Aijaz Ahmed Liver Transplant Program Division of Gastroenterology and HepatologyStanford University Medical CenterStanfordCaliforniaUSA Center for Innovation in Global Health Stanford UniversityStanfordCaliforniaUSA maple Health Group LLCNew YorkNew YorkUSA Division of Gastroenterology and Hepatology Alameda Health SystemHighland HospitalOaklandCaliforniaUSA Department of medicine Center for Liver DiseasesInova Fairfax HospitalFalls ChurchVirginiaUSA Betty and Guy Beatty Center for Integrated Research Inova Health SystemFalls ChurchVirginiaUSA

Background and Aims:The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection(HCV)is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United *** shifting—whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians—achieves non-inferior treatment outcomes with second generation direct-acting antivirals(2^(nd)Gen DAAs),may increase treatment capacity,and may facilitate greater treatment *** determined the cost effectiveness of 2^(nd)Gen DAAs with respect to interferon-based first-generation DAAs(1^(st)Gen DAAs)within a task-shifted treatment ***:Using a previously described decision-analytic markov structure,we modeled a hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a lifetime horizon,based upon our outreach clinic's HCV treatment ***-naive and treatment-experienced HCV cohorts were modeled separately,based upon our outr8each clinic's *** response to 2^(nd)Gen DAAs was modeled based on our outreach clinic's *** events,utility,costing,and transition probabilities were sourced from the ***:Driven by improved effectiveness and safety,as well as an expected increase in treatment capacity,2^(nd)Gen DAAs treatment monitored by non-physician clinicians was projected to improve health outcomes and be dominant from a cost-effective perspective versus that of 1^(st)Gen *** were consistent across all assessed patient ***:Based on an assumption of increased treatment capacity accompanying a task-shifted treatment model,2^(nd)Gen DAAs-based treatment was cost effective and cost saving as compared to 1^(st)Gen DAAs-based treatment for all HCV patient subgroups assessed.

关键词： Hepatitis C Treatment access Task shifting Cost effectiveness

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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 mong the liver transplant recipients with NASH,the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p mportantly,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 mELDmELD categories (mELDmeier methods and multivariate Cox proportional hazards ***:Overall,2,258 patients underwent *** to patients with mELDmilar 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 mELDm 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 mELDmELD 20 and higher.

关键词： Living donors Liver transplantation Waitlist model for End-Stage Liver Disease(mELD)

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Interrelationship between physical activity and depression in nonalcoholic fatty liver disease

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World Journal of Hepatology 2022年第3期14卷 612-622页

作者： Ali A Weinstein Leyla De Avila Saisruthi Kannan James m Paik Pegah Golabi Lynn H Gerber zobair m.younossi Betty and Guy Beatty Center for Integrated Research Inova Health SystemFalls ChurchVA 22042United States Global and Community Health George Mason UniversityFairfaxVA 22030United States Center for Liver Disease Department of MedicineInova Fairfax Medical CampusFalls ChurchVA 22042United States Inova medicine Inova Health SystemFalls ChurchVA 22042United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is associated with a sedentary lifestyle and depressive *** is also well established that physical inactivity and depressive symptoms are ***,an investigation of the interaction between all of these factors in NAFLD has not been previously *** To investigate the interrelationship between physical inactivity and depressive symptoms in individuals with *** Data from the Rancho Bernardo Study of Healthy Aging were utilized.589 individuals were included in the analyses(43.1%male;95.8%non-Hispanic white;aged 60.0±7.0 years).NAFLD was defined by using the hepatic steatosis index,depression using the Beck Depression Inventory,and physical activity by selfreport of number of times per week of strenuous *** generalized linear regression models with Gamma distribution were performed to investigate the proposed *** About 40%of the sample had evidence of NAFLD,9.3%had evidence of depression,and 29%were physically *** with NAFLD and depression were more likely to be physically inactive(60.7%)compared to individuals with neither NAFLD nor depression(22.9%),individuals with depression without NAFLD(37.0%),and individuals with NAFLD without depression(33.3%).After accounting for various comorbidities(i.e.,age,sex,diabetes,hypertension,obesity),individuals with NAFLD and higher levels of physical activity were at a decreased odds of having depressive symptoms[16.1%reduction(95%confidence interval:-25.6 to-5.4%),P=0.004],which was not observed in those without *** Individuals with NAFLD have high levels of physical inactivity,particularly those with depressive *** this group is at high risk for poor outcomes,practitioners should screen for the coexistence of depressive symptoms and *** group should receive appropriate interventions aimed at increasing both participation and levels of intensity of physical activ

关键词： Liver disease Outcomes research Psychiatric disorders Exercise

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Importance of fatigue and its measurement in chronic liver disease

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World Journal of Gastroenterology 2019年第28期25卷 3669-3683页

作者： Lynn H Gerber Ali A Weinstein Rohini mehta zobair m.younossi Department of medicine Beatty Center for Liver and Obesity Research Inova Health System Falls Church VA 22042 United States Center for the Study of Chronic Illness and Disability George Mason University Fairfax VA 22030 United States Beatty Center for Liver and Obesity Research Inova Health System Falls Church VA 22042 United States

The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have bee

关键词： Fatigue Chronic liver disease Non-alcoholic fatty liver diseases Nonalcoholic steatohepatitis measurement Patient-reported outcomes

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management of nonalcoholic fatty liver disease in the middle East

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World Journal of Gastroenterology 2020年第25期26卷 3528-3541页

作者： Faisal m Sanai Faisal Abaalkhail Fuad Hasan muhammad Hamed Farooqi Nawal Al Nahdi zobair m.younossi Gastroenterology Unit Department of MedicineKing Abdulaziz Medical CityJeddah 21423Saudi Arabia Department of medicine Alfaisal UniversityRiyadh 11533Saudi Arabia Department of Liver Transplant King Fahad Specialist HospitalDammam 32253Saudi Arabia Department of Internal medicine Faculty of MedicineKuwait UniversitySafat 13110Kuwait Dubai Diabetes Center Dubai Health AuthorityDubai 00000United Arab Emirates Department of Gastroenterology and Hepatology Dubai Health AuthorityRashid hospitalDubai 00000United Arab Emirates Department of medicine Inova Fairfax Medical CampusFalls ChurchVA 22042United States

The prevalence of nonalcoholic fatty liver disease(NAFLD)in the middle East is increasing in parallel to an increase in the prevalence of associated risk factors such as obesity,metabolic syndrome,and type 2 diabetes *** 20%to 30%of the patients progress to develop nonalcoholic steatohepatitis(NASH),a histological subtype of NAFLD,with features of hepatocyte injury such as hepatocyte *** can progress to fibrosis,cirrhosis,and even hepatocellular *** thus causes a substantial burden on healthcare systems and it is imperative that appropriate strategies are discussed at a regional level to facilitate effective management tailored to the needs of the *** fulfil this unmet need,expert gastroenterologists,hepatologists,and endocrinologists from the region came together in three advisory board meetings that were conducted in Saudi Arabia,United Arab Emirates,and Kuwait,to discuss current local challenges in NAFLD screening and diagnosis,and the different available management *** experts discussed the disease burden of NAFLD/NASH in the middle East;screening,diagnosis,and referral patterns in NAFLD;and available treatment options for NAFLD and *** paper summarizes the discussions and opinion of the expert panel on the management of NAFLD/NASH and also presents an extensive literature review on the topic.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis middle East Expert opinion

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Treatment strategies for chronic hepatitis C prior to andfollowing liver transplantation

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World Journal of Hepatology 2016年第1期8卷 69-73页

作者： Ryan B Perumpail Thomas A Hahambis Avin Aggarwal zobair m.younossi Aijaz Ahmed Division of Gastroenterology and Hepatology Stanford University School of MedicinePalo AltoCA 94304United States Gilead Sciences Foster CityCA 94404United States Center for Liver Diseases Department of MedicineInova Fairfax HospitalFalls ChurchVA 22042United States Betty and Guy Beatty Center for Integrated Research Inova Health SystemFalls ChurchVA 22042United States

Hepatitis C virus(HCV)-related liver disease is the leading indication for liver transplantation(LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV postLT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral(DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.

关键词： Hepatitis C virus Liver transplantation Direct acting antivirals Sustained virologic response

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Effectiveness of exercise in hepatic fat mobilization in nonalcoholic fatty liver disease: Systematic review

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World Journal of Gastroenterology 2016年第27期22卷 6318-6327页

作者： Pegah Golabi Cameron T Locklear Patrick Austin Sophie Afdhal melinda Byrns Lynn Gerber zobair m.younossi Betty and Guy Beatty Center for Integrated Research Inova Health System Department of medicine Center for Liver Disease Inova Fairfax Hospital Health Sciences Library Inova Fairfax Hospital

AIm: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) ***: Ovid-medline, Pub med, EmBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "mR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-mRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-mRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid ***: Prescribed exercise in subjects with NAFLD red

关键词： Non-alcoholic fatty liver disease Exercise Diet Fat mobilization Lifestyle modification

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慢性丙型肝炎的特异性靶向抗病毒治疗（下）

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传染病网络动态 2007年第9期 23-24页

作者： zobair m. younossi 杨露绮（编译）

HCV RNA聚合酶抑制剂除蛋白酶抑制剂之外，一直在开发很多其他针对依赖HCV RNA的RNA聚合酶的抑制剂。这些制剂中的Nm283即是一种抑制病毒RNA聚合酶的核糖核苷类似物，亦是一种病毒RNA链的终止子。Godofsky和其同事发表了一项增加1／2剂... 详细信息

HCV RNA聚合酶抑制剂除蛋白酶抑制剂之外，一直在开发很多其他针对依赖HCV RNA的RNA聚合酶的抑制剂。这些制剂中的Nm283即是一种抑制病毒RNA聚合酶的核糖核苷类似物，亦是一种病毒RNA链的终止子。Godofsky和其同事发表了一项增加1／2剂量Nm283（每天50mg至800mg）的试验结果。

关键词：抗病毒治疗慢性丙型肝炎 RNA聚合酶抑制剂 Nm283 靶向异性蛋白酶抑制剂核苷类似物

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Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

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World Journal of Hepatology 2015年第29期7卷 2871-2879页

作者： Andy Liu Ryan B Perumpail Radhika Kumari zobair m.younossi Robert J Wong Aijaz Ahmed Albert Einstein College of medicine Division of Gastroenterology and Hepatology Stanford University School of Medicine Center for Liver Diseases Department of MedicineInova Fairfax Hospital Division of Gastroenterology and Hepatology Alameda Health System - Highland Hospital Campus

Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.

关键词： Overt hepatic encephalopathy Lactulose Rifaximin Hepatic encephalopathy Covert hepaticencephalopathy

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