Staff Profile

@article{Julien2020,

title = {Projected prevalence and mortality associated with alcohol-related liver disease in the USA, 2019-40: a modelling study.},

author = {Jovan Julien and Turgay Ayer and Emily Bethea and Elliot B. Tapper and Jagpreet Chhatwal},

url = {https://pubmed.ncbi.nlm.nih.gov/32504584/},

doi = {10.1016/S2468-2667(20)30062-1},

issn = {2468-2667},

year  = {2020},

date = {2020-06-01},

journal = {The Lancet. Public health},

volume = {5},

pages = {e316--e323},

abstract = {Alcohol-related liver disease is the leading indication for liver transplantation in the USA. After remaining stable for over three decades, the number of deaths due to alcohol-related liver disease has been increasing as a result of increased high-risk drinking. We aimed to project trends in alcohol-related cirrhosis and deaths in the USA up to 2040 and assess the effect of potential changes in alcohol consumption on those trends. In this modelling study, we developed a multicohort state-transition (Markov) model of high-risk alcohol drinking patterns and alcohol-related liver disease in high-risk drinking populations born in 1900-2016 in the USA projected up to 2040. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, National Institute of Alcohol Abuse and Alcoholism, US National Death Index, National Vital Statistics System, and published studies. We modelled trends in alcohol-related liver disease under three projected scenarios: the status quo scenario, in which current trends continued; a moderate intervention scenario, in which trends in high-risk drinking reduced to 2001 levels under some hypothetical moderate intervention; and a strong intervention, in which trends in high-risk drinking decreased by 3·5% per year under some hypothetical strong intervention. The primary outcome was to project deaths associated with alcohol-related liver disease from 2019 to 2040 for each pattern of alcohol consumption under the different scenarios. Our model closely reproduced the observed trends in deaths due to alcohol-related liver disease from 2005 to 2018. Under the status quo scenario, age-standardised deaths due to alcohol-related liver disease are expected to increase from 8·23 (95% uncertainty interval [UI] 7·92-9·29) per 100 000 person-years in 2019 to 15·20 (13·93-16·19) per 100 000 person-years in 2040, and from 2019 to 2040, 1 003 400 (95% CI 896 800-1 036 200) people are projected to die from alcohol-related liver disease, resulting in 1 128 400 (1 113 200-1 308 400) DALYs by 2040. Under the moderate intervention scenario, age-standardised deaths due to alcohol-related liver disease would increase to 14·49 (95% UI 12·55-14·57) per 100 000 person-years by 2040, with 968 100 (95% UI 845 600-975 900) individuals projected to die between 2019 and 2040-35 300 fewer deaths than under the status quo scenario (a 3·5% decrease). Whereas, under the strong intervention scenario, age-standardised deaths due to alcohol-related liver disease would peak at 8·65 (95% UI 8·12-9·51) per 100 000 person-years in 2024 and decrease to 7·60 (6·96-8·10) per 100 000 person-years in 2040, with 704 300 (95% CI 632 700-731 500) individuals projected to die from alcohol-related liver disease in the USA between 2019 and 2040-299 100 fewer deaths than under the status quo scenario (a 29·8% decrease). Without substantial changes in drinking culture or interventions to address high-risk drinking, the disease burden and deaths due to alcohol-related liver disease will worsen in the USA. Additional interventions are urgently needed to reduce mortality and morbidity associated with alcohol-related liver disease. American Cancer Society and the Robert Wood Johnson Health Policy Research Fellowship.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bloom2019,

title = {Computed Tomography Findings as a Novel Predictor of Alcohol-Associated Hepatitis Outcomes.},

author = {Patricia P Bloom and Amirkasra Mojtahed and Emily Bethea and Sally A Knooihuizen and Jin Choi and Jules L Dienstag and Raymond T Chung and Chin Hur},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31363954},

doi = {10.1007/s10620-019-05721-4},

issn = {1573-2568},

year  = {2020},

date = {2020-01-01},

journal = {Digestive diseases and sciences},

volume = {65},

number = {1},

pages = {312-321},

abstract = {Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. Our aim was to identify CT features that predict outcomes in AH. We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeeBP2019,

title = {Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients with Alcohol-Associated Hepatitis.},

author = {Brian P Lee and Sumeyye K. Samur and Ozden Onur Dalgic and Emily Bethea and Michael R Lucey and Ethan Weinberg and Christine Hsu and Mary E Rinella and Gene Y Im and Oren K Fix and George Therapondos and Hyosun Han and David W Victor and Michael D Voigt and Sheila Eswaran and Norah A Terrault and Jagpreet Chhatwal},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30998988},

doi = {10.1053/j.gastro.2019.04.012},

issn = {1528-0012},

year  = {2019},

date = {2019-08-01},

journal = {Gastroenterology},

volume = {157},

number = {2},

pages = {472-480},

abstract = {Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial-many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on model for end-stage liver disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life-years lost attributable to alcohol use after receiving the liver transplant. Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life-years, compared to an average life expectancy of 1.46 life-years for patients offered delayed liver transplants (4.49-fold increase). Net survival benefit from early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared to 3.62 years for patients with sustained alcohol use after transplantation (7.23 life-years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use following transplant. These findings support early liver transplantation for patients with severe AH. The survival benefit was maintained in all simulated extreme scenarios, but should be confirmed in prospective studies. Sustained alcohol use following transplantation significantly reduced but did not eliminate the benefits of early transplantation-strategies are needed to prevent and treat post-transplantation use of alcohol.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chhatwal2019a,

title = {The impact of direct-acting anti-virals on the hepatitis C care cascade: identifying progress and gaps towards hepatitis C elimination in the United States.},

author = {Jagpreet Chhatwal and Qiushi Chen and Emily Bethea and Chin Hur and Anne C Spaulding and Fasiha Kanwal},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31115920},

doi = {10.1111/apt.15291},

issn = {1365-2036},

year  = {2019},

date = {2019-07-01},

journal = {Alimentary pharmacology \& therapeutics},

volume = {50},

number = {1},

pages = {66-74},

abstract = {The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct-acting anti-virals (DAAs). Up-to-date estimates of the cascade are needed to monitor progress, identify key gaps and inform policy. To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest. We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence. By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade. Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2019,

title = {Changes in hepatitis C burden and treatment trends in Europe during the era of direct-acting antivirals: a modelling study.},

author = {Qiushi Chen and Turgay Ayer and Emily Bethea and Fasiha Kanwal and Xiaojie Wang and Mark Roberts and Yueran Zhuo and Stefano Fagiuoli and Jorg Petersen and Jagpreet Chhatwal},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31189677},

doi = {10.1136/bmjopen-2018-026726},

issn = {2044-6055},

year  = {2019},

date = {2019-06-01},

journal = {BMJ open},

volume = {9},

pages = {e026726},

abstract = {Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically changed the treatment paradigm. Our aim was to project temporal trends in HCV diagnosis, treatment and disease burden in France, Germany, Italy, Spain and the UK. A mathematical simulation model of natural history of HCV infection. HCV-infected patients defined based on country-specific age, fibrosis and genotype distributions. HCV screening practice and availability of different waves of DAA treatment in each country. Temporal trends in the number of patients who achieve sustained virological response (SVR), fail treatment (by drug regimen) and develop advanced sequelae from 2014 to 2030 in each country. We projected that 1 324 000 individuals would receive treatment from 2014 to 2030 in the five European countries and 12 000-37 000 of them would fail to achieve SVR. By 2021, the number of individuals cured of HCV would supersede the number of actively infected individuals in France, Germany, Spain and the UK. Under status quo, the diagnosis rate would reach between 65% and 75% and treatment coverage between 65% and 74% by 2030 in these countries. The number of patients who fail treatment would decrease over time, with the majority of those who fail treatment having been exposed to non-structural protein 5A inhibitors. In the era of DAAs, the number of people with HCV who achieved a cure will exceed the number of viraemic patients, but many patients will remain undiagnosed, untreated, fail multiple treatments and develop advanced sequelae. Scaling-up screening and treatment capacity, and timely and effective retreatment are needed to avail the full benefits of DAAs and to meet HCV elimination targets set by WHO.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{CHHATWAL2018819,

title = {Hep C Calculator: an online tool for cost-effectiveness analysis of DAAs},

author = {Jagpreet Chhatwal and Qiushi Chen and Emily Bethea and Mary Ann Ladd and Peter P. Mueller and Yvan Hutin and Rakesh Aggarwal},

url = {http://www.sciencedirect.com/science/article/pii/S2468125318302814},

doi = {https://doi.org/10.1016/S2468-1253(18)30281-4},

issn = {2468-1253},

year  = {2018},

date = {2018-12-01},

urldate = {2018-12-01},

journal = {The Lancet Gastroenterology \& Hepatology},

volume = {3},

number = {12},

pages = {819},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bethea2018,

title = {Cost-effectiveness of Transplanting HCV-Infected Livers into Uninfected Recipients with Preemptive Antiviral Therapy.},

author = {Emily Bethea and Sumeyye K. Samur and Fasiha Kanwal and Turgay Ayer and Chin Hur and Mark S Roberts and Norah Terrault and Raymond T Chung and Jagpreet Chhatwal},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30138735},

doi = {10.1016/j.cgh.2018.08.042},

issn = {1542-7714},

year  = {2018},

date = {2018-08-01},

journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},

abstract = {Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any (HCV-negative or HCV-positive) liver. Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores that may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. Using a Markov-based mathematical model, we found transplanting HCV-positive livers in HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chhatwal2017d,

title = {Transplanting Hepatitis C Virus-positive Livers Into Hepatitis C Virus-egative Patients With Preemptive Antiviral Treatment: A Modeling Study.},

author = {Jagpreet Chhatwal and Sumeyye K. Samur and Emily Bethea and Turgay Ayer and Fasiha Kanwal and Chin Hur and Mark S Roberts and Norah Terrault and Raymond T Chung},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29222916},

doi = {10.1002/hep.29723},

issn = {1527-3350},

year  = {2018},

date = {2018-06-01},

journal = {Hepatology (Baltimore, Md.)},

volume = {67},

number = {6},

pages = {2085-2095},

abstract = {Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with \>90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: 1) willing to accept any (HCV-negative or HCV-positive) liver versus 2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when MELD was ≥ 20, and the benefit was highest at MELD 28 (0.172 additional life years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, i.e. Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chhatwal2018a,

title = {Reply to Expanding Donor Pool for Liver Transplantation by Utilizing Hepatitis C Virus-Infected Donors for Uninfected Recipients.},

author = {Jagpreet Chhatwal and Emily Bethea and Sumeyye K. Samur and Raymond T Chung},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29672882},

doi = {10.1002/hep.30042},

issn = {1527-3350},

year  = {2018},

date = {2018-04-01},

journal = {Hepatology (Baltimore, Md.)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bethea2017,

title = {Should we treat acute hepatitis C? A decision and cost-effectiveness analysis},

author = {Emily Bethea and Qiushi Chen and Chin Hur and Raymond T Chung and Jagpreet Chhatwal},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29059461},

doi = {10.1002/hep.29611},

issn = {1527-3350},

year  = {2018},

date = {2018-03-01},

journal = {Hepatology (Baltimore, Md.)},

volume = {67},

number = {3},

pages = {837-846},

abstract = {It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re-evaluate acute HCV management in the era of direct-acting antiviral agents (DAAs). In this study a microsimulation model was developed to analyze the tradeoffs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long-term outcomes such as quality-adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost effectiveness ratio (ICER) was $19,991 per QALY, demonstrating that treatment of acute HCV was cost-effective using a willingness-to-pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost-saving, increasing QALYs by 0.03 and decreasing costs by $3655. Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6 week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}