Donor liver small droplet macrovesicular steatosis is associated with reduced graft survival after liver transplantation

Modern hepatic steatosis classification includes large droplet macrovesicular (L-MaS), small droplet macrovesicular (S-MaS) and true microvesicular (MiS). Based on previous classification simply describing macrovesicular and microvesicular steatosis, donor livers with ≤30% of hepatocytes with macrosteatosis, which should represent L-MaS, are considered safe to be transplanted, while microsteatosis is usually not considered a risk factor for graft loss. Microsteatosis is differently associated with the type and severity of hepatocellular damage, according to the presence or absence of hepatitis c virus (HCV) infection. Thus, we analyzed the impact of steatosis on post-transplant liver graft survival, separately in HCV-RNA negative (HCV-) and positive (HCV+) recipients. Methods: We retrospectively analyzed 206 routinely performed pre-ischemia graft biopsies in consecutive adult patients submitted to deceased-donor liver transplantation in our Center between 2001 and 2011. Steatosis was defined as follows: L-MaS as one or few large vacuoles in the cytoplasm with nuclear displacement; S-MaS as few or discrete vacuoles in the cytoplasm without nuclear displacement; MiS as intracytoplasmic accumulation of numerous, tiny and undiscernable vesicles with a foamy appearance. Graft ATP content was measured by bioluminescence assay. Results: Only 2 grafts had MiS and were excluded from the statistical analysis. The maximum L-MaS was 40% (6 grafts). A S-MaS ≥40% was present in 9 grafts. The median follow-up was 2432 and 2264 days respectively for the HCV- (n=122) and HCV+ (n=82) patients. At Cox regression analysis, in the HCV- group S-Mas >15% was independently associated with overall graft loss (HR 2.386 95% CI 1.176-4.841, p=0.005), after normalization for several recipient, donor and intraoperative variables. No association of graft survival was found with L-MaS in the HCV- group and with both S-MaS and L-MaS in the HCV+ group. In HCV-, but not in HCV+ recipients, the first three post-operative days serum AST peak positively correlated with S-MaS. Graft S-MaS >15% was associated with reduced graft ATP content. Conclusions: a donor liver graft S-MaS >15% is associated with low graft ATP content. S-MaS is associated with clinical signs of severe ischemia reperfusion damage and with reduced graft survival only in HCV- recipients. These data are relevant for organ allocation and because the percentage of HCV- recipients is rapidly increasing