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

Am J Physiol Gastrointest Liver Physiol. 2019 May 1;316(5):G608-G614. doi: 10.1152/ajpgi.00335.2018. Epub 2019 Mar 14.


Dynamic liver function assessment by the [13C]methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic cytochrome P-450 (CYP) 1A2 activity. One proven strategy for preoperative risk assessment 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 nontumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in nontumor tissues (35.5, 15.9-54.4 µU/mg) compared with hepatocellular adenomas (7.35, 1.2-32.5 µU/mg), hepatocellular carcinomas (0.18, 0.0-2.0 µU/mg), or colorectal liver metastasis (0.17, 0.0-2.1 µU/mg). In nontumor 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 with the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), whereas 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. NEW & NOTEWORTHY The cytochrome P-450 (CYP) 1A2-dependent maximal liver function capacity test reflects the overall functional capacity of the liver. To which extent hepatocellular tumors harbor CYP1A2 activity and thus contribute to the maximal liver function capacity test outcome is unknown. We here show that hepatocellular adenomas but not hepatocellular carcinomas or colorectal liver metastasis contain significant residual CYP1A2 activity. These findings are important for an improved preoperative volume-function analysis and an accurate surgical risk assessment in hepatocellular adenoma cases.

Keywords: CYP1A2; LiMAx test; volume-function analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Liver Cell* / enzymology
  • Adenoma, Liver Cell* / pathology
  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / enzymology
  • Carcinoma, Hepatocellular* / pathology
  • Colorectal Neoplasms* / pathology
  • Cytochrome P-450 CYP1A2 / analysis*
  • Female
  • Humans
  • Liver / enzymology
  • Liver / pathology
  • Liver Function Tests / methods*
  • Liver Neoplasms* / enzymology
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / secondary
  • Male
  • Middle Aged
  • Organ Size
  • Preoperative Care / methods*
  • Prognosis
  • Reproducibility of Results
  • Risk Assessment / methods
  • Tumor Burden


  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2