Patterns of hepatotoxicity after chemotherapy for colorectal cancer liver metastases

Abstract 

Aim

The aim of this study was to assess chemotherapy associated hepatotoxicity after 3 months' treatment and to correlate patterns of hepatotoxicity with perioperative morbidity.

Methods

Liver specimens of 50 patients with liver metastases from colorectal cancer receiving XELOX or FOLFOX4 for six cycles and 13 specimens of non-chemotherapy patients subjected to liver resection were analyzed. Different patterns of hepatotoxicity were evaluated according to widely accepted pathohistological scores. Furthermore, the histomorphological findings were correlated with perioperative morbidity.

Results

Steatosis grades did not differ among the chemotherapy treated groups and non-chemotherapy patients. Chemotherapy showed an independent effect on fibrosis stage. Age and chemotherapy were independently associated with sinusoidal dilatation. Centrilobular vein fibrosis correlated with administration of chemotherapy. Higher fibrosis stages were associated with increased transfusion requirements.

Conclusion

XELOX and FOLFOX4 do not correlate with the development of steatosis or steatohepatitis. We do not detect a difference in liver injury between the XELOX and FOLFOX4 group. Although 5-fluorouracil based chemotherapy may cause profound changes in liver parenchyma, it can be safely applied. However, age and oxaliplatin predispose for the development of sinusoidal dilatation; therefore caution must be taken in old patients treated with oxaliplatin.

Keywords: Oxaliplatin, 5-Fluorouracil, Sinusoidal dilatation, Chemotherapy, Perioperative morbidity, Colorectal cancer liver metastases

Abbreviations: NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, NAS, NAFLD activity score, SOS, sinusoidal obstruction syndrome, EORTC, European Organisation for Research on Treatment of Cancer, mCRC, metastatic colorectal cancer