Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients

Abstract

Background. No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim. We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods. We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results. The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks. Conclusions. In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.

Alcohol and Liver Clock Disruption Increase Small Droplet Macrosteatosis, Alter Lipid Metabolism and Clock Gene mRNA Rhythms, and Remodel the Triglyceride Lipidome in Mouse Liver

“…Notably, small droplet macrosteatosis is associated with reduced hepatic ATP content and poorer outcomes in liver transplant patients, suggesting a link to mitochondrial dysfunction (Ferri et al, 2019). Previously, we have shown that alcohol impairs mitochondrial bioenergetics (Young et al, 2006;King et al, 2014) and damages mtDNA (Venkatraman et al, 2004), with other studies reporting clock control of mitochondrial function (Peek et al, 2013;Jacobi et al, 2015).…”

Single‐cell profiling reveals distinct immune phenotypes that contribute to ischaemia‐reperfusion injury after steatotic liver transplantation

“…Steatotic liver is a common type of ECD. However, such organs are more prone to preservation injury and graft dysfunction, resulting in a poor prognosis after liver transplantation 6‐8 . It has been proposed that steatotic livers are more susceptible to ischaemia‐reperfusion (I/R) injury, which impairs liver regeneration and is a major cause of liver damage 6,9 .…”

The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity

“…Permanent histological sections were analyzed to assess and classify the donor liver steatosis according to the Brunt classification [ 3 , 4 , 48 ]: Ld-MaS, as one or few large vacuoles in the cytoplasm with nuclear displacement in an eccentric location of the cell; Sd-MaS, as few and discrete fat vacuoles that were smaller than half of the cell and did not displace the nucleus ( Figure 2 ). True microvesicular steatosis was defined as the presence of innumerable tiny indiscernible lipid vesicles diffusely distributed in the cytoplasm causing its foamy appearance as previously illustrated also by Ferri et al [ 49 ]. The extent of each type of steatosis was expressed as a percentage of each type of steatotic hepatocyte compared to all hepatocytes.…”