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Steatosis and islet graft survival

Cristiane B Leitao², Antonio Westphalen³, Eduardo M.L. Peixoto¹, Leonor G. Mireles-Zavala¹, Vincenzo Lauriola¹, Karina Bernetti¹, Camillo Ricordi¹, Rodolfo Alejandro¹

¹Diabetes Research Institute, University of Miami, Miami, FL; ³Radiology Department, University of California, San Francisco, CA, United States; ²Endocrine Division, Endocrine Division Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

This study aimed to evaluate the association between islet graft survival and the fat content of the liver in islet transplant (ITx) recipients. The liver fat content was evaluated by MRI [fat liver score = (signal intensity on in-phase - opposed-phase images)/signal intensity on in-phase images * 100 and divided by the average spleen signal intensity]in 33 type 1 diabetes mellitus (DM) ITx recipients. Variations in liver fat content according to islet function were evaluated by pared t test with Bonferroni correction. Kaplan Meier curves and Cox-regression analysis were performed with time-to-graft failure as the dependant variable and fat liver content ≥3% (which corresponds to histological steatosis grade 1) was an independent one, with adjustments to number of transplants, cold ischemia time, HLA mismatches and use of exenatide. The fat liver content did not change significantly overtime (P >0.05). A tendency to earlier islet failure in patients with some degree of liver fat was observed, but only in those with functional grafts after 40 months (overall period P = 0.52; after 40 months P = 0.057). The presence of fat liver was associated with earlier graft loss after adjustments to possible confounders (OR = 13.78; P = 0.024) In this sample the fat liver content did not change significantly overtime. However, the presence of fat liver (fat liver index corresponding to histological steatosis grade 1) was associated with earlier graft loss even after adjustments to variables known to be associated with ITx Prospective clinical trials may confirm the cause-effect association between liver fat and islet failure and evaluate if its reduction may prolong islet graft survival.