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Objective: In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition., Methods: This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ 2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050., Results: A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) ( P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) ( P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) ( P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) ( P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant., Conclusions: The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)