De-novo Autoimmune Hepatitis (De-novo AIH) after Liver Transplantation (LT) is an entity recently described and considered rare. Its importance relies on a severe clinical course, with graft loss in the short term, non-response to immunosuppressant therapies and requiring retransplantation even more than once. The Colombian population has a higher incidence of autoimmune liver diseases when compared to the literature, with a more aggressive clinical course and poorer response to classical immunosuppressive therapies requiring LT. This suggests a unique genetic component of the Colombian population that determines specific management and prognosis. The HLA (loci DR 3 * and DR 4 *) has been associated with De-novo AIH, especially in children, but no studies have been published in Hispanic Adults to date. A retrospective observational study. The overall objective of this study was to determine the allelic frequencies of HLA (loci DR 3 * and DR 4 *) in donor livers of a Colombian population of patients with LT and its association with De-novo AIH. Out of 260 adult patients with LT at Cardioinfantil Foundation, eight were identified with De-novo AIH, all with graft loss and indication for liver retransplantation, 2 of them with graft loss for the second time in less than one year. HLA DR 4 was identified in all donors of patients who developed De-novo AIH. The association between HLA DR-4 and De-novo AIH after LT establishes a precedent in the history of liver transplantation not only in Colombia but the world and requires immediate attention.