Although liver transplantation is lifesaving for patients with end-stage liver disease (ESLD), the scarcity of cadaveric livers constrains its public health impact. Each year, approximately 6,000 patients undergo liver transplantation in the U.S., while roughly 2,000 are removed from the waitlist due to death or clinical deterioration.25 These 2,000 patients are a small fraction of the estimated 30,000 people that die each year from complications of ESLD26, suggesting the scarcity of livers may cause a potentially large number of ESLD patients to never be waitlisted. Indeed, the few available studies have estimated that less than 5% of potential transplant candidates are ever waitlisted.27,28 There are very limited data on factors that influence who among the population of patients with ESLD is listed for transplantation, and almost none of the data are population- based. Some factors, such as gender and cause of ESLD can be studied in local settings. However, the absence of nationally representative population-based data has prevented an in-depth evaluation of how systemic factors, such as geographic variations in supply and demand influence listing practices for ESLD patients. Thus, a population-based approach to studying ESLD is needed to bridge these unmet knowledge gaps. This proposal aims to establish such a population-based dataset of ESLD, and to use this new resource to test the central hypothesis that traditional research, focusing only on patients listed for liver transplantation, fails to capture the true impact of listing practices and allocation policies. The work could shift the paradigm by which future ESLD and transplant outcomes research is conducted to encompass population-level impacts of policies and practices. This work will: a) employ two novel algorithms to generate a national cohort of ESLD patients to be used for present and future ESLD outcomes research1,10~ b) identify potentially modifiable factors (e.g. listing practices) that can improve access to transplantation and outcomes among all potential transplant candidates~ and c) teach the applicant to use several new epidemiologic and demographic methods to foster his goal of become a leading physician-scientist focused on improving outcomes for ESLD patients.
The specific aims are to: 1) identify patient and geographic factors associated with listing for transplantation among ESLD patients~ 2) evaluate the total impact of local mismatches between liver supply and demand~ and 3) examine how rates of listing for liver transplantation influence adverse patient outcomes among both waitlisted patients and all local ESLD patients. The research structure at the University of Pennsylvania and the Clinical Center for Epidemiology and Biostatistics, supplemented by the didactic coursework offered through the Perelman School of Medicine at the University of Pennsylvania offer the optimal environment within which the candidate will complete this work and foster his career as a clinician and independent investigator. Dr. Goldberg has assembled a mentorship team with expertise in epidemiologic, health services, and hepatology research, and an Advisory Committee with a longstanding track record of research and mentorship.

Public Health Relevance

Current research on patients with end-stage liver disease utilizes databases that only capture patients listed for liver transplantation, neglecting the lare pool of potential transplant candidates who never get listed. By identifying and examining a population-based cohort of patients with end-stage liver disease, this work seeks to improve the management of all patients with end-stage liver disease by evaluating how system-level interventions, including practices of listing patients for transplantation and allocating organs, impact all people with end-stage liver disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK098272-01A1
Application #
8633209
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2013-09-14
Project End
2018-07-31
Budget Start
2013-09-14
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$155,110
Indirect Cost
$11,490
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Zhang, Frank; Mamtani, Ronac; Scott, Frank I et al. (2016) Increasing use of prescription drugs in the United Kingdom. Pharmacoepidemiol Drug Saf 25:628-36
Goldberg, David S; French, Benjamin; Lewis, James D et al. (2016) Liver transplant center variability in accepting organ offers and its impact on patient survival. J Hepatol 64:843-51
Mamtani, Ronac; Lewis, James D; Scott, Frank I et al. (2016) Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study. PLoS Med 13:e1002007
Goldberg, D S; Trotter, J D (2016) The Gift That Keeps on Giving: Increasing Donation Rates by Offering Incentives. Am J Transplant 16:2512-3
Goldberg, David; French, Benjamin; Newcomb, Craig et al. (2016) Patients With Hepatocellular Carcinoma Have Highest Rates of Wait-listing for Liver Transplantation Among Patients With End-Stage Liver Disease. Clin Gastroenterol Hepatol 14:1638-1646.e2
Goldberg, David S; French, Benjamin; Sahota, Gurvaneet et al. (2016) Use of Population-Based Data to Demonstrate How Waitlist-Based Metrics Overestimate Geographic Disparities in Access to Liver Transplant Care. Am J Transplant :
Scott, Frank I; Horton, Daniel B; Mamtani, Ronac et al. (2016) Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity. Gastroenterology 151:120-129.e5
Khungar, Vandana; Goldberg, David Seth (2016) Liver Transplantation for Cholestatic Liver Diseases in Adults. Clin Liver Dis 20:191-203
Scott, Frank I; Mamtani, Ronac; Haynes, Kevin et al. (2016) Validation of a coding algorithm for intra-abdominal surgeries and adhesion-related complications in an electronic medical records database. Pharmacoepidemiol Drug Saf 25:405-12
Nobel, Yael R; Forde, Kimberly A; Wood, Linda et al. (2015) Racial and ethnic disparities in access to and utilization of living donor liver transplants. Liver Transpl 21:904-13

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