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Updated: Aug 3, 2026

Ex Situ Normothermic Machine Perfusion of Donor Livers
Published on: May 26, 2015
Donor Liver Small Droplet Macrovesicular Steatosis Is Associated With Increased Risk for Recipient Allograft
Won-Tak Choi1, Kuang-Yu Jen, Dongliang Wang
1Departments of *Pathology ‡Surgery, Division of Transplantation, University of California at San Francisco, San Francisco, CA †Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY.
Abstract:
Although donor livers with <30% large droplet macrovesicular steatosis (MaS) and/or small droplet MaS (irrespective of percentage) are considered safe to use, this consensus is based on variable definitions of MaS subtypes and/or without a reproducible scoring system. We analyzed 134 donor liver biopsies from allografts transplanted at University of California at San Francisco between 2000 and 2015 to determine whether large and/or small droplet MaS is a risk factor for poor outcomes. Large droplet MaS was defined as a fat droplet occupying greater than one half of an individual hepatocyte, with nuclear displacement, and scored as the percentage of total parenchymal area replaced by large fat droplets on ×40 magnification. Small droplet MaS was defined as 1 to several discrete fat droplets, each occupying less than one half of an individual hepatocyte, and scored as the percentage of remaining hepatocytes (ie, hepatocytes not occupied by large fat droplets) containing small fat droplets on ×200 magnification (ie, small droplet MaS is the percentage of "remaining hepatocytes" with small fat droplets, and "remaining hepatocytes" is defined as 100% minus percent large droplet MaS). Thus, total MaS equals the sum of large and small droplet MaS, which cannot exceed 100%. Electronic medical records were reviewed to determine outcomes. There was an increased risk for acute cellular rejection (hazard ratio=2.5, P=0.0108) and bile duct loss suggestive of chronic ductopenic rejection (hazard ratio=2.4, P=0.0130) in donor livers with ≥30% small droplet MaS. Large droplet MaS (up to 60%) was not associated with adverse outcomes. Patient survival was not adversely affected by steatosis. Excellent agreement on the estimation of large (weighted κ=0.682) and small droplet MaS (weighted κ=0.780) was achieved. Our approach to donor steatosis scoring can identify liver allograft recipients at increased risk for rejection and highlights the importance of distinguishing between small and large droplet MaS in this evaluation.
Insights
Donor livers with significant small droplet macrovesicular steatosis (MaS) increase rejection risk, but large droplet MaS does not. Distinguishing between MaS types is crucial for liver transplant outcomes.
Area of Science:
- Hepatology
- Transplantation immunology
- Pathology
Background:
- Current consensus on donor liver steatosis (MaS) safety uses variable definitions.
- A reproducible scoring system for MaS subtypes is lacking.
- Donor liver quality impacts transplant outcomes.
Purpose of the Study:
- To determine if large or small droplet MaS is a risk factor for poor liver allograft outcomes.
- To establish a reproducible scoring system for MaS subtypes.
- To assess the impact of MaS on acute cellular rejection and chronic ductopenic rejection.
Main Methods:
- Analysis of 134 donor liver biopsies from allografts transplanted between 2000-2015.
- Defined and scored large droplet MaS (fat droplet >1/2 hepatocyte) and small droplet MaS (fat droplet <1/2 hepatocyte).
- Reviewed electronic medical records for outcomes including rejection and patient survival.
Main Results:
- Donor livers with ≥30% small droplet MaS showed increased risk of acute cellular rejection (HR=2.5) and bile duct loss (HR=2.4).
- Large droplet MaS (up to 60%) was not associated with adverse outcomes.
- Excellent inter-observer agreement was achieved for both large (κ=0.682) and small droplet MaS (κ=0.780) scoring.
Conclusions:
- Distinguishing between small and large droplet MaS is vital for evaluating donor liver quality.
- A reproducible scoring system for MaS can identify liver allograft recipients at increased risk for rejection.
- Small droplet MaS, not large droplet MaS, is a significant risk factor for adverse transplant outcomes.
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