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

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International Journal of Clinical Oncology Aims and scope Submit manuscript

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.

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Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

ICGR15 :

Retention rate of indocyanine green at 15 min

AFP:

Alpha-fetoprotein

PNI:

Prognostic Nutritional Index

TACE:

Transarterial chemoembolization

mALBI:

Modified albumin bilirubin

ROC:

Receiver operating characteristic

SD:

Standard deviation

IQR:

Interquartile range

CI:

Confidence interval

NS:

Not significant

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 20K17665 (Dr. Yoshihiro Shirai).

Author information

Authors and Affiliations

  1. Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Mitsuru Yanagaki, Yoshihiro Shirai, Ryoga Hamura, Tomohiko Taniai, Yoshiaki Tanji, Koichiro Haruki, Kenei Furukawa, Shinji Onda, Hiroaki Shiba & Toru Ikegami

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  1. Mitsuru Yanagaki
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  2. Yoshihiro Shirai
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  3. Ryoga Hamura
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Correspondence to Yoshihiro Shirai.

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The authors declare no conflicts of interest in association with the present study.

Ethics statement

The Ethics Committee of The Jikei University School of Medicine approved this study (Approval No.: 27–177 [8062]).

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Supplementary Information

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10147_2021_2111_MOESM1_ESM.tif

Supplementary file1 ROC curve of the FIB-4 index for the survival status at 5 years of follow-up. The optimal cutoff value for the FIB-4 index was 3.44, with an AUC of 0.611 (95% CI, 0.519–0.703; P = 0.017). AUC, area under the curve; CI, confidence interval; FIB-4, fibrosis-4; ROC, receiver operating characteristic analysis. (TIF 368 KB)

10147_2021_2111_MOESM2_ESM.tif

Supplementary file2 ROC curve of the FIB-4 index, serum PIVKA-II, and PIVKA-II–FIB-4 index score for the survival status at 5 years of follow-up. The AUC of the PIVKA-II–FIB-4 index score (AUC, 0.661; 95% CI, 0.568–0.755; P = 0.001) for the survival status at the 5-year follow-up was greater than that of the FIB-4 index (AUC, 0.625; 95% CI, 0.528–0.722; P = 0.011) and serum PIVKA-II (AUC, 0.603; 95% CI, 0.508–0.698; P = 0.037). AUC, area under the curve; CI, confidence interval; FIB-4, fibrosis-4; PIVKA-II, Protein Induced by Vitamin K Absence or Antagonist-II; ROC, receiver operating characteristic analysis. (TIF 429 KB)

Supplementary file3 (DOCX 16 KB)

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Yanagaki, M., Shirai, Y., Hamura, R. et al. Novel combined fibrosis-based index predicts the long-term outcomes of hepatocellular carcinoma after hepatic resection. Int J Clin Oncol 27, 717–728 (2022). https://doi.org/10.1007/s10147-021-02111-7

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