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Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is a usual finding in patients with differentiated thyroid carcinoma. The aim of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA) whole-body scans.A total of 720 PA and 172 PT I-131 scans in a total of 732 patients with differentiated thyroid carcinoma were retrospectively reviewed. Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0 to 4. The correlation between the liver and thyroid remnant uptake score, dose of radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST), liver ultrasonography, presence of metastatic foci, and recurrent disease were examined.Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of 172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively correlated with the dose of administered I-131 and increased levels of serum AST and ALT. Liver uptake scores of patients with hepatosteatosis were significantly higher than all study groups. However, no evidence of a relationship between diffuse visualization of liver and serum thyroglobulin levels, uptake score of thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and recurrence rate could be demonstrated.The lack of correlation between hepatic radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or thyroid remnants suggests that this finding may be related to factors other than thyroid tissue. The positive correlation between administered RAI dose, hepatic enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI uptake may be related to different mechanisms as well.