The spatial variability of hepatic fat reduction in potential living liver donors with hepatic steatosis (HS) who undergo lifestyle modification has not been investigated. Here, we aimed to examine the intra- and inter-segmental variability of changes in liver attenuation on computed tomography (CT) in potential living liver donors with HS after diet modification and exercise. A total of 87 living liver donor candidates (30.5±7.0 years; 74 men) with biopsy-proven macrovesicular fat≥10% were included. All underwent diet modification and exercise to improve HS, baseline and follow-up unenhanced CT scans and liver biopsies. Attenuation and its variability (mean and standard deviation, respectively, Hounsfield units) in segmental, lobar, superficial, deep, and whole areas of liver were measured across 32 different regions-of-interest on both baseline and follow-up CT. At baseline, the right lobe and superficial areas of liver showed significantly lower and more variable attenuation than left lobe and deep areas. Greater variability was noted in subjects with more severe HS. Mean interval changes in liver attenuation and variability before and after diet modification and exercise were 13.7 (range, -10.6-46.2) and 4.7 (1.3-10.6), respectively. The mean interval change in liver attenuation was significantly higher in right lobe than in left (14.7 vs. 12.7; P<0.001), and in superficial areas than in deep areas (14.0 vs. 13.4; P=0.02). Greater variability and larger interval changes in liver attenuation were noted in those who responded (≥ 20% decrease in macrovesicular fat) to diet modification and exercise than in those who did not. In conclusion, potential living liver donors with HS show significant intra- and inter-segmental variability in hepatic fat reduction on CT before and after diet modification and exercise.This article is protected by copyright. All rights reserved.