Novel combined fibrosis-based index predicts the long-term outcomes of hepatocellular carcinoma after hepatic resection

Abstract

Aim: Liver fibrosis influences liver regeneration and surgical outcomes. The fibrosis-4 (FIB-4) index is strongly associated with liver fibrosis and cirrhosis. This study aimed to examine the prognostic significance of the combination of FIB-4 index and Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) (PIVKA-II-FIB-4 index score) in patients who underwent curative resection for hepatocellular carcinoma (HCC).

Methods: We included 284 patients who underwent elective hepatic resection for HCC between January 2000 and December 2018. We retrospectively investigated how FIB-4 index is related to disease-free survival and overall survival.

Results: According to a receiver operating characteristic (ROC) analysis, the optimal cutoff value of the FIB-4 index was 3.44. In a multivariate analysis, high PIVKA-II and FIB-4 index values were independent predictors of both disease-free survival (P = 0.013 and P = 0.005, respectively) and overall survival (P = 0.048 and P < 0.001, respectively). We classified the PIVKA-II and FIB-4 index levels into two groups (high vs. low) and calculated a new score (PIVKA-II-FIB-4 index score; 0-2) by the sum of each measurement (high, 1; low, 0). The 5 year overall survival rates of patients with PIVKA-II-FIB-4 index scores of 0, 1, and 2 were 84.9, 74.4, and 47.1%, respectively (P < 0.001).

Conclusion: The combination of the preoperative PIVKA-II and FIB-4 index may be a prognostic factor of HCC after hepatic resection, suggesting that the combined score is useful in assessing the liver fibrosis status in cancer cases.

Keywords: Fibrosis-4 index; Hepatic resection; Hepatocellular carcinoma; PIVKA-II; Prognostic factor.