Zeitschrift für Karzinogenese und Mutagenese

Abstrakt

Oxaliplatin-Related Hepatic Sinusoidal Obstruction Syndrome: Updated Biological Pathway Analysis

Kazumi Fujioka

Oxaliplatin is a backbone drug of many regimens for colorectal cancer and colorectal liver metastasis. The author previously described a thorough review of the literature on oxaliplatin-induced hepatic complications focusing on Sinusoidal Obstruction Syndrome (SOS), Nodular Regenerative Hyperplasia (NRH), and Focal Nodular Hyperplasia (FNH) in patients with colorectal cancer and colorectal liver metastasis and emphasized Liver Stiffness Measurement (LSM) as a novel predictor by elastography, recently reviewed the mechanism of oxaliplatin-induced SOS along with potential therapeutic strategy. In this article, the current knowledge and trends of oxaliplatin-induced SOS along with updated biological pathway analysis have been reviewed. Additionally, an association between oxaliplatin-induced SOS and atherosclerotic status has been described. It is plausible that oxaliplatin-induced liver injuries may have the broad spectrum from acute liver injury to long-term liver complications such as NRH. Based on the evidence, gene expression profile revealed several biological pathways including oxidative stress, inflammation, hepatic fibrosis/ Hepatic Stellate Cell (HSC) activation, coagulation, angiogenic, and hypoxic factor for oxaliplatin-induced SOS. In particular, inflammatory pathway is significantly upregulated, suggesting a main driving factor of hepatotoxicity by oxaliplatin chemotherapy and a close relationship between oxaliplatin-induced SOS and atherosclerosis. Similar to the association between chronic liver disease (NAFLD/NASH and HCV infection) and atherosclerosis, oxaliplatin-induced SOS may have both liver and systemic inflammation and lead to SOS-related atherosclerosis status. It may be significant to assess the vascular endothelial and smooth muscle cell function using Flow-Mediated Vasodilation (FMD) and Nitroglycerin-Mediated Vasodilation (NMD) procedures for the evaluation of SOS-related atherosclerosis condition in oxaliplatin-induced SOS setting.