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2015 ASTS Vanguard Prize Recipients

Karim Halazun

Karim Jarir Halazun, MD
Emory Transplant Center

Synopsis: Patients with hepatocellular carcinoma (HCC) have been prioritized to receive livers for over a decade. However, because of the wide geographic variation in access to organs in the United States, patients with HCC have different waiting times and resultant pre-transplant treatment algorithms and possibly outcomes depending on where they are listed. We decided to assess these differences by comparing outcomes in long waiting times regions (LWTR, regions 5 and 9) and short waiting times regions (SWTR, regions 3 and 10) by analyzing national data from the United Network for Organ Sharing (UNOS) database. Our results suggest that early access to liver transplantation for patients with HCC is detrimental to overall survival despite decreasing the risk of waitlist dropout. Improved survival in the LWTR existed both on an intent-to-treat analysis and in a post-transplant survival analysis, despite a higher proportion of T3 patients being transplanted in the LWTR. Listing and being transplanted in the LWTR was associated with better outcome in multivariable analysis, conferring a 20% greater chance of improved survival when compared to listing in a SWTR. In conclusion, our study provides population-based evidence that expediting patients with HCC to transplant at too fast a rate adversely affects outcomes. Because overall waiting time is an independent predictor of poor outcome, we would suggest that further iterations in allocation policy toward HCC be considered.
Paulo Martins

Paulo N. Martins, MD, PhD
Massachusetts General Hospital/Harvard Medical School

Synopsis: This paper, "Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. J Hepatol. 2014 Jun;60(6):1172-9," was the result of a collaborative effort of two transplant centers (Massachusetts General Hospital and University Medical Center Groningen in The Netherlands). A total of 128 liver transplant patients were followed prospectively to correlate pre-transplant histology of the biliary tree with non-anastomotic strictures (ischemic cholangiopathy-IC). The pathophysiology of ischemic cholangiopathy is not well defined, and its occurrence is unpredictable. We aimed to investigate the histological changes of the distal bile duct that will be associated with IC after transplant. It is known that the bile duct blood supply plays a pivotal role in the development of biliary strictures; however, early changes in the biliary vascular plexus have not been investigated before. In addition, it is well known that the peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. Thus, we hypothesized that damage to peribiliary glands and vascular plexus before transplant may play a role in the development of IC and be used as a predictor tool. We found surprisingly that most of the grafts (91.8%) had major biliary epithelial loss (>50% of circumference) even before transplant as a result of cold ischemia damage. However, IC-related strictures occurred in only 16.4% (median follow-up of 17 months), demonstrating the regenerative capacity of bile ducts. In addition, peri-luminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p <0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed IC-related strictures, compared to grafts without IC-related strictures (>50% loss in 50.0% vs. 9.8%, respectively; p = 0.004), indicating it is a strong predictor of major biliary injury and later strictures. In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed IC-related strictures, compared to grafts without IC-strictures (>50% vascular changes in 57.1% vs. 20.3%; p = 0.006). As conclusions, we found that major biliary damage (with major epithelial loss) occurs even before reperfusion, differently from what was previously believed. Injury of peribiliary glands and vascular plexus before transplantation are strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply play a role in the development of biliary strictures.