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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Clinical Investigator Award (CIA) (K08)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Niu, Bolin; Forde, Kimberly A; Goldberg, David S (2015) Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data. Pharmacoepidemiol Drug Saf 24:107-11
Scott, Frank I; Vajravelu, Ravy K; Bewtra, Meenakshi et al. (2015) The benefit-to-risk balance of combining infliximab with azathioprine varies with age: a markov model. Clin Gastroenterol Hepatol 13:302-309.e11
Goldberg, David S; Reese, Peter P; Amaral, Sandra et al. (2014) Reframing the impact of combined heart-liver allocation on liver transplant wait-list candidates. Liver Transpl 20:1356-64
Goldberg, David S; Krok, Karen; Batra, Sachin et al. (2014) Impact of the hepatopulmonary syndrome MELD exception policy on outcomes of patients after liver transplantation: an analysis of the UNOS database. Gastroenterology 146:1256-65.e1
Goldberg, D S; Batra, S; Sahay, S et al. (2014) MELD exceptions for portopulmonary hypertension: current policy and future implementation. Am J Transplant 14:2081-7
Goldberg, David S; Olthoff, Kim M (2014) Standardizing MELD Exceptions: Current Challenges and Future Directions. Curr Transplant Rep 1:232-237
Goldberg, David S; French, Benjamin; Abt, Peter L et al. (2014) Superior survival using living donors and donor-recipient matching using a novel living donor risk index. Hepatology 60:1717-26
Sulewski, Michael E; Wolf, Joshua H; Hasz, Richard et al. (2014) Combined heart-liver transplantation; implications for liver-alone wait list mortality. Transplantation 98:e45-7