Background <p>While the value of Des-γ-carboxy prothrombin in hepatocellular carcinoma diagnosis has been widely acknowledged, whether or how Des-γ-carboxy prothrombin could be used in recurrence evaluation remains largely unexplored.</p> Methods <p>We performed a multicenter retrospective analysis including an Exploration Cohort (1074 patients, 5133 Des-γ-carboxy prothrombin measurements) and a Validation Cohort (263 patients, 612 Des-γ-carboxy prothrombin measurements) to investigate whether Des-γ-carboxy prothrombin could evaluate patients’ prognosis. We introduced the Des-γ-carboxy prothrombin dynamic rate as a normalized quantitative measurement of Des-γ-carboxy prothrombin dynamic change. Des-γ-carboxy prothrombin dynamic rates were further applied in a high-risk liver cirrhosis patient cohort (PreCar Cohort, 542 liver cirrhosis patients, 2023 Des-γ-carboxy prothrombin measurements).</p> Results <p>Here, we show a post-operative decrease of Des-γ-carboxy prothrombin in the Exploration Cohort, making the Des-γ-carboxy prothrombin threshold in diagnosis unsuitable for prognosis, while Des-γ-carboxy prothrombin dynamic rates significantly associate with recurrence risk. Categorizing patients based on Des-γ-carboxy prothrombin dynamic rates and final concentrations shows that patients negative for both exhibit the best median recurrence-free survival and patients positive for both show the worst median recurrence-free survival. Patients with consistently positive status have a significantly lower median recurrence-free survival compared to those whose status reverted to negative. These findings are validated in the Validation Cohort. Furthermore, the Des-γ-carboxy prothrombin dynamic rates in the PreCar Cohort can identify an additional 28% of cirrhosis patients progressing to hepatocellular carcinoma.</p> Conclusions <p>These results expand on the clinical utilization of the hepatocellular carcinoma diagnosis biomarker, Des-γ-carboxy prothrombin, by proposing a quantification measurement of Des-γ-carboxy prothrombin dynamics to monitor hepatocellular carcinoma recurrence. This measurement is not limited in prognosis but can also improve the sensitivity of early hepatocellular carcinoma screening.</p>

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Des-γ-carboxy Prothrombin in hepatocellular carcinoma post-operative recurrence risk evaluation

  • Xinting Pan,
  • Yang Zhou,
  • Zhenli Li,
  • Pengfei Guo,
  • Jianyang Zeng,
  • Xiuqing Dong,
  • En Hu,
  • Liman Qiu,
  • Zhixiong Cai,
  • Geng Chen,
  • Xiaolong Liu

摘要

Background

While the value of Des-γ-carboxy prothrombin in hepatocellular carcinoma diagnosis has been widely acknowledged, whether or how Des-γ-carboxy prothrombin could be used in recurrence evaluation remains largely unexplored.

Methods

We performed a multicenter retrospective analysis including an Exploration Cohort (1074 patients, 5133 Des-γ-carboxy prothrombin measurements) and a Validation Cohort (263 patients, 612 Des-γ-carboxy prothrombin measurements) to investigate whether Des-γ-carboxy prothrombin could evaluate patients’ prognosis. We introduced the Des-γ-carboxy prothrombin dynamic rate as a normalized quantitative measurement of Des-γ-carboxy prothrombin dynamic change. Des-γ-carboxy prothrombin dynamic rates were further applied in a high-risk liver cirrhosis patient cohort (PreCar Cohort, 542 liver cirrhosis patients, 2023 Des-γ-carboxy prothrombin measurements).

Results

Here, we show a post-operative decrease of Des-γ-carboxy prothrombin in the Exploration Cohort, making the Des-γ-carboxy prothrombin threshold in diagnosis unsuitable for prognosis, while Des-γ-carboxy prothrombin dynamic rates significantly associate with recurrence risk. Categorizing patients based on Des-γ-carboxy prothrombin dynamic rates and final concentrations shows that patients negative for both exhibit the best median recurrence-free survival and patients positive for both show the worst median recurrence-free survival. Patients with consistently positive status have a significantly lower median recurrence-free survival compared to those whose status reverted to negative. These findings are validated in the Validation Cohort. Furthermore, the Des-γ-carboxy prothrombin dynamic rates in the PreCar Cohort can identify an additional 28% of cirrhosis patients progressing to hepatocellular carcinoma.

Conclusions

These results expand on the clinical utilization of the hepatocellular carcinoma diagnosis biomarker, Des-γ-carboxy prothrombin, by proposing a quantification measurement of Des-γ-carboxy prothrombin dynamics to monitor hepatocellular carcinoma recurrence. This measurement is not limited in prognosis but can also improve the sensitivity of early hepatocellular carcinoma screening.