Introduction Chemotherapy associated liver injury (CALI) has been associated with increased morbidity and mortality in patients undergoing major hepatectomy to treat colorectal liver metastases (CRLM). In addition a link has recently been made between CALI and poorer long term disease specific outcome. The aim of this review was to determine the pathological effect of specific chemotherapy regimens on the hepatic parenchyma as well as surgical morbidity, mortality and overall survival.
Methods A literature search of MEDLINE, EMBASE and the Cochrane Library identified 14 619 potentially relevant reports. Of these 37 full text reports which included patients only with CRLM and provided either histological data or patient outcome data were considered suitable for inclusion in this review. For each report data relating to study design characteristics, histological scoring of the liver parenchyma and peri-operative outcomes were extracted using a standardised proforma. Study quality was assessed using the Newcastle-Ottawa score for non-randomised studies and the grade of evidence assessed according to the Oxford centre for Evidence Based Medicine scale. A meta-analysis was performed utilising the random effects model of DerSimmonian and Laird. Results are reported as RR (±95% CI). Statistical significance was set at p<0.05.
Results No association could be demonstrated between the use of pre-operative chemotherapy and the development of hepatic steatosis >30%. The presence of steatohepatitis was associated with the use of pre-operative Irinotecan based chemotherapy (RR 3.45; 95% CI 1.12 to 10.62; p=0.03). Calculating the number needed to harm suggests that one in every 12 patients treated with Irinotecan based chemotherapy could be expected to develop steatohepatitis. Oxaliplatin based chemotherapy regimens are associated with grade 2 or greater sinusoidal injury (RR 4.36; 95% CI 1.12 to 10.62; p=0.03) with a number needed to harm of 8. The use of Bevacizumab alongside Oxaliplatin reduces the risk of grade 2 or greater sinusoidal injury.
Conclusion The use of pre-operative chemotherapy is associated with an increased risk of injury to the liver parenchyma in patients with CRLM. This injury occurs in a regimen specific manner with Irinotecan being associated with steatohepatitis whereas Oxaliplatin is associated with sinusoidal injury. This injury may have implications on the functional reserve of the liver following major hepatic resection.
Competing interests None declared.
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