Combined AFP-CRUT with microvascular invasion accurately predicts mortality risk in patients with hepatocellular carcinoma following curative liver resection

Abstract

Aims: To establish and validate an equation of α-fetoprotein (AFP) change rate over unit time (AFP-CRUT) as a potential predictor of survival after resection in patients with hepatocellular carcinoma (HCC). Methods: The AFP-CRUT was constructed based on dynamic variation in AFP over time and then categorized into quintiles. The area under the receiver operating characteristic (ROC) curve showed the performance for survival prediction. Results: As independent risk factors associated with mortality, microvascular invasion (MVI) (p = 0.003) and AFP-CRUT quintiles (p = 0.048) were combined to enhance the predictive effect. The highest 5-year overall survival rate following curative liver resection (93%) was observed in patients with MVI absent and AFP-CRUT in quintile 1 (49.64 to 209.61). In contrast, the lowest 5-year overall survival (7%) was obtained in quintile 5 (−469.29 to 6.45) with MVI present. In validation cohorts at both 12 and 24 months, AFP-CRUT performed well as a potential prognostic biomarker. Conclusions: Combining AFP-CRUT quintiles with MVI may predict significantly improved outcomes and enhance the predictive power for patient responses to therapeutic intervention.

Keywords:

• α-fetoprotein
• curative liver resection
• dynamic parameter
• hepatocellular carcinoma
• microvascular invasion
• overall survival

Financial & competing interests disclosure

The authors were supported by grants from the Scientific Research Foundation of Wenzhou, Zhejiang Province, China (grant numbers: H20090014, Y20090269), Health Bureau of Zhejiang Province (grant number: 2010KYB070), Research Foundation of Education Bureau of Zhejiang Province (grant number: Y201009942), Fresh Talent Program for Science and Technology Wenzhou Medical University (grant numbers: wyx201401011, wyx201401087, wyx201401009 and wyx201401085), Research Funds for Tian Qing Liver Diseases (grant number: TQGB20120057) and Project of New Century 551 Talent Nurturing in Wenzhou. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Patients with curative liver resection (CLR) have poor long-term prognosis and a high incidence of recurrence.

• The level of AFP is the most common serum marker to diagnose hepatocellular carcinoma (HCC) and predict the recurrence of HCC.

• Elevated AFP suggests the recurrence of HCC after CLR.

• The prognosis of patients who underwent CLR for HCC is constrained by the lack of an efficient instrument.

• The absolute level of AFP is characterized by poor assay sensitivity and specificity, especially during the early stages of the disease.

• The presence of microvascular invasion (MVI) was the most statistically significant independent risk factor affecting disease-specific and recurrence-free survival in patients with HCC after CLR.

• We recommend to first construct the dynamic parameter of AFP in the patients who underwent CLR for HCC and combine MVI with dynamic AFP and stratify the data to predict prognostic results more effectively.

• The performance of dynamic AFP was great in validation cohorts.

Notes