Primary sclerosing cholangitis (PSC) is a chronic liver disease that has no treatment and is an otherwise fatal disease without liver transplantation. Patients with PSC face unique complications as compared to other patients with end-stage liver disease, including cholangiocarcinoma (CCA), cholangitis from biliary strictures, and complications such as colon cancer from concomitant inflammatory bowel disease. The current model for allocation of livers, instituted on February 27th, 2002, relies on a patient's Model for End Stage Liver Disease (MELD) score, which accounts for a patient's serum INR, creatinine, and bilirubin. The MELD score places more weight on the INR and creatinine, although in patients with PSC the bilirubin is disproportionately elevated. This fact, along with the fact that complications such as CCA are not captured by the MELD data elements, leads us to believe that the MELD score may place patients with PSC at a survival disadvantage. If this is true, then this may serve as a basis for a policy change in how livers are allocated. For patients with PSC on the waitlist, their risk of death may be higher for two reasons. Either the risk of death for a given MELD score is higher for patients with PSC, or in patients with PSC, the MELD score rises more slowly, making patients less likely to receive a transplant and thereby exposed for a longer duration to the risks of clinical deterioration and removal from the waitlist.
Our first aim will address this primary research question in three ways. We will develop two Cox proportional hazard models, one accounting for all of a patient's MELD scores while on the waitlist, and another adjusting only for MELD at listing. We will also perform logistic regression to evaluate the clinically important outcome of death vs. transplant.
Our second aim will serve to determine the frequencies with which potential liver transplant recipients are removed from the waitlist due to clinical deterioration among those in whom the reasons for withdrawal are unspecified in UNOS data. By collecting patient level data from individual transplant centers, we will be able to calculate the extent of this outcome misclassification and thereby guide quantitative sensitivity analyses of our primary models in Aim I. Lastly, we will evaluate whether introduction of the MELD system for liver allocation was associated with changes in rates of living donor liver transplantation among patients with PSC relative to corresponding rates among patients without PSC. This analysis is needed as differential rates of referral for living donor transplant among patients with and without PSC could affect the extent to which diagnosis may influence the outcomes in Aim I. The proposed research project will be in the context of the applicant working towards a Masters of Science in Clinical Epidemiology, whereby didactic learning in the classroom, focusing on fundamentals of epidemiology, study design, and statistical and analytic methods of research will enhance and guide the research process of the applicant. The long-term objectives of the applicant for this project are to collect and analyze the data, prepare manuscripts for publication, and build upon the data as part of a future application for a K award.

Public Health Relevance

The allocation of organs for liver transplantation has major public health implications in that decisions must be made as to how we allocate a scarce resource. It is critical that we practice within a system that is equitable, and does not disadvantage one group of patients as a result of their disease status. If it is found that patients with primary sclerosing cholangitis are disadvantaged by the current liver allocation system, then this will form a foundation for which large-scale policy changes are considered to bring about a fairer system of organ transplantation.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-2 (M1))
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Podskalny, Judith M,
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University of Pennsylvania
Internal Medicine/Medicine
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United States
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Goldberg, David S; Camp, Amanda; Martinez-Camacho, Alvaro et al. (2013) Risk of waitlist mortality in patients with primary sclerosing cholangitis and bacterial cholangitis. Liver Transpl 19:250-8
Goldberg, David S; Lewis, James D; Halpern, Scott D et al. (2013) Validation of a coding algorithm to identify patients with hepatocellular carcinoma in an administrative database. Pharmacoepidemiol Drug Saf 22:103-7
Goldberg, David; French, Benjamin; Trotter, James et al. (2013) Underreporting of liver transplant waitlist removals due to death or clinical deterioration: results at four major centers. Transplantation 96:211-6
Goldberg, David S; Halpern, Scott D; Reese, Peter P (2013) Deceased organ donation consent rates among racial and ethnic minorities and older potential donors. Crit Care Med 41:496-505
Goldberg, D; Lewis, Jd; Halpern, Sd et al. (2012) Validation of three coding algorithms to identify patients with end-stage liver disease in an administrative database. Pharmacoepidemiol Drug Saf 21:765-769
Ruebner, R; Goldberg, D; Abt, P L et al. (2012) Risk of end-stage renal disease among liver transplant recipients with pretransplant renal dysfunction. Am J Transplant 12:2958-65
Goldberg, D; Bittermann, T; Makar, G (2012) Lack of standardization in exception points for patients with primary sclerosing cholangitis and bacterial cholangitis. Am J Transplant 12:1603-9
Goldberg, David; French, Benjamin; Abt, Peter et al. (2012) Increasing disparity in waitlist mortality rates with increased model for end-stage liver disease scores for candidates with hepatocellular carcinoma versus candidates without hepatocellular carcinoma. Liver Transpl 18:434-43
Bittermann, Therese; Makar, George; Goldberg, David (2012) Exception point applications for 15 points: an unintended consequence of the share 15 policy. Liver Transpl 18:1302-9
Goldberg, David; French, Benjamin; Thomasson, Arwin et al. (2011) Waitlist survival of patients with primary sclerosing cholangitis in the model for end-stage liver disease era. Liver Transpl 17:1355-63

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