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. 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 improv 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 #
5K08DK098272-02
Application #
8733677
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
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$154,789
Indirect Cost
$11,466
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Goldberg, David S; Newcomb, Craig; Gilroy, Richard et al. (2017) Increased Distance to a Liver Transplant Center Is Associated With Higher Mortality for Patients With Chronic Liver Failure. Clin Gastroenterol Hepatol 15:958-960
Goldberg, David S; Levine, Matthew; Karp, Seth et al. (2017) Share 35 changes in center-level liver acceptance practices. Liver Transpl 23:604-613
Goldberg, David; Levy, Cynthia; Yimam, Kidist et al. (2017) Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium. Clin Gastroenterol Hepatol :
Murken, Douglas R; Peng, Allison W; Aufhauser Jr, David D et al. (2017) Same policy, different impact: Center-level effects of share 35 liver allocation. Liver Transpl 23:741-750
Doshi, Sahil D; Bittermann, Therese; Schiano, Thomas D et al. (2017) Waitlisted Candidates With Polycystic Liver Disease Are More Likely to be Transplanted Than Those With Chronic Liver Failure. Transplantation 101:1838-1844
Bushyhead, Daniel; Goldberg, David (2017) Use of Hepatitis C-Positive Donor Livers in Liver Transplantation. Curr Hepatol Rep 16:12-17
Goldberg, David; Ditah, Ivo C; Saeian, Kia et al. (2017) Changes in the Prevalence of Hepatitis C Virus Infection, Nonalcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients With Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation. Gastroenterology 152:1090-1099.e1
Goldberg, D S; French, B; Sahota, G 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 16:2903-2911
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, 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

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