Clinicn Investigator, Assc Prf Surgery, Mass General Research Institute

Associate Professor of Surgery Harvard Medical School

Visiting Surgeon Transplant Surgery, Massachusetts General Hospital

MD University of Pennsylvania 1997

adult; liver transplantation; living donors; patient selection; treatment outcome

The Yeh Laboratory has the following ongoing research projects:

• Ex vivo liver perfusion: In spite of the organ shortage, many deceased donor livers are discarded as untransplantable though some may have potentially reversible defects such as excessive ischemic injury and steatosis. We are collaborating with Martin Yarmush, MD, PhD, and Korkut Uygun, PhD, at Shriners Burns Hospital, who have developed a defatting cocktail that decreases macrosteatosis in cultured hepatocytes and reverses their pre-existing adenosine triphosphate (ATP) deficiencies and poor response to ischemia reperfusion injury.
  
  Using our experience in perfusing livers with excessive ischemic injury (donated after cardiac death with prolonged warm ischemia times), we are using the defatting cocktail in two models:  discarded steatotic human livers with a blood reperfusion to simulate transplantation and a fatty liver rat model with actual transplantation of treated steatotic rat livers. This perfusion system also serves as an ideal platform to study hepatocyte lipid metabolism.

---

• Strategies to improve liver regeneration: The liver has a remarkable capacity for regeneration, but at some minimal mass, it fails to regenerate, leaving the host to die of liver failure. This minimal mass has limited our ability to perform hepatic resections for benign and malignant disease, recover patients with fulminant hepatic failure and perform segmental transplantation that would allow single livers to save multiple recipients.
  
  In partial hepatectomy models in mice and baboons,inflammatory markers such as IL-6 levels, circulating neutrophil counts and macrophage infiltration into the liver are increased in animals destined to die of liver failure because of liver regeneration failure.
  
  We are utilizing various knock-out mice and blocking or depleting antibodies to test the effect of inhibiting these pathways on the ability of the liver to regenerate and the mouse to survive. We have also developed a small segment liver failure model in primates as a preclinical model for testing the efficacy of drugs, extra-corporeal liver assist devices and auxiliary liver xenotransplantation to promote native liver regeneration

---

• Disparities in access to transplantation: It is estimated that only 20% of patients with end stage liver disease and less than 40% of end stage renal disease patients make it to the wait list for transplantation, and listing rates vary widely across the country.
  
  Using the Scientific Registry of Transplant Recipients, together with census data, death certificate data and the United States Renal Data System (USRDS) database, we look at the effect of competition, allocation and distribution algorithms, race and socioeconomic status on disparities in access to solid organ transplantation