Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

PLoS One. 2017 Apr 13;12(4):e0175359. doi: 10.1371/journal.pone.0175359. eCollection 2017.

Abstract

Background and aims: Antithrombin III (ATIII) has been reported to be associated with liver pathologies and was shown to predict outcome in patients undergoing liver resection for hepatocellular carcinoma. We now aimed to assess whether perioperative ATIII-activity could predict postoperative outcome in patients without underlying liver disease, as well as in a routine clinical setting of patients undergoing hepatic resection.

Methods: ATIII-activity was evaluated preoperatively and on the first (POD1) and fifth day after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC). We further aimed to prospectively validate our results in a set of 177 consecutive patients undergoing hepatic resection.

Results: Patients developing postoperative liver dysfunction (LD) had a more pronounced postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1 significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity was determined using ROC analysis. This cut-off was vital to identify high-risk patients for postoperative LD, morbidity, severe morbidity and mortality (P<0.001, respectively) with a highly accurate negative predictive value of 97%, which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our independent validation cohort. Further, mCRC patients below our cut-off suffered from a significantly decreased overall survival (OS) at 1 and 3 years after surgery (P = 0.011, P = 0.025).

Conclusions: The routine laboratory parameter ATIII-activity on POD1 independently predicted postoperative LD and was associated with clinical outcome. Patients with a postoperative ATIII-activity <61.5% might benefit from close monitoring and timely initiation of supportive therapy.

Trial registration: ClinicalTrials.gov NCT01700231.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombin III / metabolism*
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / surgery
  • Colorectal Neoplasms* / blood
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Failure* / blood
  • Liver Failure* / etiology
  • Liver Failure* / mortality
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / secondary
  • Liver Neoplasms* / surgery
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Postoperative Complications* / blood
  • Postoperative Complications* / mortality
  • Predictive Value of Tests
  • Retrospective Studies
  • Survival Rate

Substances

  • Antithrombin III

Associated data

  • ClinicalTrials.gov/NCT01700231

Grants and funding

The authors received no funding for this work.