Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis.

Dynamic liver function assessment by the (13)C-methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic CYP1A2 activity. One proven strategy for preoperative risk assessement in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery. The CYP1A2 activity analysis of neoplastic lesions and adjacent non-tumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in non-tumor tissues (35.5, 15.9-54.4 microU/mg) as compared to hepatocellular adenomas (7.35, 1.2-32.5 microU/mg), hepatocellular carcinomas (0.18, 0.0-2.0 microU/mg) or colorectal liver metastasis (0.17, 0.0-2.1 microU/mg), respectively. In non-tumor liver tissue a gradual decline in CYP1A2 activity with exacerbating fibrosis was observed. The CYP1A2 activity differences were also reflected in CYP1A2 protein signals in the assessed hepatic tissues. Volume-function analysis showed a minimal deviation compared to the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), while a difference of 11.9% was observed for hepatocellular adenomas. These findings are important for a refined preoperative volume-function analysis and improved surgical risk assessment in hepatocellular adenoma cases with low LiMAx values.