Background and Aims: Alterations in liver histology influence the liver´s capacity to regenerate, but the relevance of each of the different changes rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. Results: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs. 17 d, P˂0.01), low histological risk stage 2 (13 vs. 15 d, P˂0.01) and low pathological tumor risk (13 vs. 15 d, P˂0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight (r=−0.1 and r=−0.08, respectively), and future liver remnant (r=−0.15 and r=−0.06, respectively). Conclusion: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.