The developing clinical problem of chemotherapy-induced hepatic injury

Chemotherapy is being administered to an increasing number of patients with colorectal liver metastases (CRLM), whether they have resectable disease or not. Although this may be appropriate to downstage patients with unresectable disease, and offers theoretical advantages to those who have resectable disease, there is a price to be paid in the development of chemotherapy-induced hepatic injuries (CIHI). These include chemotherapy-associated fatty liver diseases and sinusoidal injuries. The main chemotherapeutic agents currently used in the adjuvant setting for colorectal carcinoma, and the neoadjuvant treatment of CRLM include 5-flurouracil, oxaliplatin and irinotecan, and while there are non-specific and overlapping injury profiles, oxaliplatin does appear to be primarily associated with sinusoidal injury and irinotecan with steatohepatitis. In this review, the rationale for administering chemotherapy to patients with CRLM is presented, and the problems this brings are outlined. The specific injury patterns will be detailed, as well as the data correlating specific chemotherapy regimens to these injury patterns. Finally, the clinical outcomes of patients with CRLM who undergo neoadjuvant chemotherapy followed by hepatic resection will be considered. The need for methods to identify patients at risk of CIHI and to recognize established CIHI prior to surgery will be emphasized.