J. Davis1, S. Fuller1, S. Kubal1, J. Fridell1, A. J. Tector1, R. S. Mangus1 1Indiana University School Of Medicine,Transplant Division, Dept Of Surgery,Indianapolis, IN, USA
Introduction:
Deceased organ donor liver transplant allografts with steatosis have an increased risk of primary non-function and initial poor function post-transplant. A large percentage of donor livers have significant steatosis. Previous research suggests improvement in steatosis in the immediate post-transplant period. This study compares reperfusion and early post-transplant surveillance biopsies, and correlates the results with initial graft function and long-term outcomes.
Methods:
Records of all liver transplants (LTs) performed at a single center over a 14-year period were reviewed. The original biopsies were reviewed by experienced liver pathologists. Liver biopsies are obtained at the time of transplant and 3 days after transplant. Total steatosis is calculated as the sum of both micro- and macrovesicular steatosis, and is categorized into four study groups: (1) none (0%), (2) mild (<10%), (3) moderate (10-20%) and (4) severe (>20%). For this analysis, change in liver steatosis is calculated as moving from one study group to another. Early post transplant liver function is assessed by biochemical analysis of liver enzymes (alanine aminotransferase (ALT); liver injury), total bilirubin (TB; excretion), international normalized ratio (INR; synthesis). Long-term survival is assessed using Cox regression analysis.
Results:
Data were available for 1572 adult subjects. Among the patients with steatosis, there was a significant and rapid decrease in steatosis. The median group change was greatest for severe steatosis groups (Group 3, >20%: -1.54; Group 2, 10 to 20%: -0.93; Group 1, 1 to 10%: -0.47 (p<0.001). Moderate and severe steatosis was associated with more acute liver injury (p<0.05 for days 1 to 6), and delayed graft function (higher TB and INR (p<0.05 on days 1, 3)). These values decreased for all study groups until they were similar by day 7 (ALT) and day 14 (TB and INR). Systemically, steatotic groups demonstrated an acute decrease in glomerular filtration rate (GFR) from 1 to 3 days post transplant, ranging from -12 to -22% change, compared to only a -5% change for the nonsteatotic group. Graft survival was worse at all time periods for moderate and severe steatosis livers. Subgroup analysis was employed to identify groups that have a more dynamic decrease in steatosis. Those groups with better clearance of severe steatosis included recipients who were younger, more obese, male, and those with fatty liver disease.
Conclusion:
These results confirm a marked post-transplant decrease in allograft steatosis that occurs within 3 days of transplant. Subgroup analysis suggests that younger male patients who are obese or have fatty liver disease are more able to clear steatosis in this period. Allografts with moderate to severe steatosis have worse early injury, delayed graft function and worse early and late survival. Steatotic grafts are associated with a substantial acute decrease in renal function early post transplant.