Chemotherapy-associated Liver Injury prior Surgery of Hepatic Colorectal Metastases – Comparison of Functional and Histopathological Damage

Abstract

Background: Chemotherapy prior liver resection of colorectal liver metastases (CLM) implies the risk of chemotherapy-associated liver injury (CALI) leading to increased postoperative morbidity and mortality. Methods: Retrospective analysis of patients with CLM prior resection. Preoperative assessment of liver function by LiMAx test. Histologic staging of resected tumor-free liver tissue. Analysis of 12-month history of chemotherapy prior surgery including the regime, the number of cycles and the therapy-free interval. Results: A total of 204 patients were analyzed. The majority (n=127; 62 %) had received previous chemotherapy. Impaired LiMAx results were determined in 49% of patients after chemotherapy. The extent of LiMAx impairment was dependent on number of oxaliplatin cycles, therapy-free interval and obesity in multivariate analysis. Patients with impaired LiMAx showed regeneration during chemotherapy cessation. Chemotherapy increased the incidence of steatosis (>33%; 29 vs. 17%) as well as of mild fibrosis (62 vs. 45%). The LiMAx was markedly decreased in steatosis (335 vs. 375 μg/kg/h, P=0.024), steatohepatitis (292 vs. 372 μg/kg/h, P=0.003), and severe fibrosis (318 vs. 395 μg/kg/h, P=0.001). While the degree of steatosis was associated with a short therapy-free interval, the degree of fibrosis was increased by the number of cycles. Conclusion: The LiMAx test enables preoperative assessment of CALI. Acute injury with steatohepatitis deteriorates LiMAx more severely than chronic injury with fibrosis.