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Preoperative HALP score is a prognostic factor for intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection: association with sarcopenia and immune microenvironment

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Abstract

Background

The hemoglobin–albumin–lymphocyte–platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited.

Methods

This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors.

Results

Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0 cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075).

Conclusions

We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment.

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Abbreviations

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CT:

Computed tomography

DFS:

Disease-free survival

γ-GTP:

γ-Glutamyl transpeptidase

HALP:

Hemoglobin, albumin, lymphocyte and platelet

HR:

Hazard ratio

HBV-Ag:

Hepatitis B surface-antigen

HCV-Ab:

Hepatitis C virus-antibody

ICC:

Intrahepatic cholangiocarcinoma

OS:

Overall survival

PLR:

Platelet-to-lymphocyte ratio

PNI:

Prognostic nutritional index

ROC:

Receiver operating characteristic

SMI:

Skeletal muscle mass index

TILs:

Tumor-infiltrating lymphocytes

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Acknowledgements

We would like to thank Ms. Yuko Kubota, and Ms. Miki Nakashima for their technical support. We also thank H. Nikki March, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was supported by the Medical Research Encouragement Prize from The Japan Medical Association and by JSPS KAKENHI grant number JP-19K09198. The funding sources had no role in the collection, analysis, or interpretation of the data or in the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan

    Katsuya Toshida, Shinji Itoh, Yuki Nakayama, Yuriko Tsutsui, Yukiko Kosai-Fujimoto, Takahiro Tomino, Shohei Yoshiya, Yoshihiro Nagao, Noboru Harada & Tomoharu Yoshizumi

  2. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Kenichi Kohashi & Yoshinao Oda

Authors
  1. Katsuya Toshida
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  2. Shinji Itoh
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Contributions

KT participated in the study conception and design, analysis, and drafting of the article. SI participated in the study conception and design, and in the critical revision of the manuscript. YN, TT, SY, YN, NH, and KK participated in the data acquisition, analysis, and interpretation. YO and TY participated in the analysis and in the critical revision of the manuscript.

Corresponding author

Correspondence to Shinji Itoh.

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Conflict of interest

K.T. and the other co-authors have no conflict of interest.

Ethics approval and informed consent

This retrospective study was approved by the ethics committee of Kyushu University (approval code: 2021–467).

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Supplementary Information

Below is the link to the electronic supplementary material.

10147_2023_2358_MOESM1_ESM.pptx

Supplementary file1 Receiver operating characteristic curve analysis to determine the optimal cutoff value of the HALP score. Area under the curve value was 0.63 (PPTX 78 KB)

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Toshida, K., Itoh, S., Nakayama, Y. et al. Preoperative HALP score is a prognostic factor for intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection: association with sarcopenia and immune microenvironment. Int J Clin Oncol 28, 1082–1091 (2023). https://doi.org/10.1007/s10147-023-02358-2

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