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Nutrition and metabolism status alteration in advanced hepatocellular carcinoma patients treated with anti-PD-1 immunotherapy

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Abstract

Purpose

The aim of this study was to evaluate the nutrition and metabolism status alteration during immunotherapy in advanced hepatocellular carcinoma (HCC) patients.

Methods

Patients with advanced HCC who participated in the clinical trials of single-agent anti-PD-1 immunotherapy or sorafenib were retrospectively included. We analyzed self-comparison of the nutritional and metabolic indices of patients in the anti-PD-1 and sorafenib treatment group. We conducted mutual-comparison of the mentioned indices between the disease progression group and disease control group among anti-PD-1 treatment patients. We further analyzed those indices with statistical differences by partial correlation and survival analysis.

Results

Both self-comparison before and after treatment in the anti-PD-1 group and mutual-comparison of disease progression and the control group showed significant differences in multiple indices, but we did not observe significant differences in the sorafenib group. Strikingly, albumin (ALB)/prognostic nutritional index (PNI, calculated by serum albumin and lymphocyte count) decreased distinctly in the immunotherapy disease progression group patients. However, changes in ALB/PNI were not significant in disease progression patients from the sorafenib group or in the disease control patients with immunotherapy. Partial correlation analysis suggested that ALB and PNI were positively correlated with the efficacy of immunotherapy. Furthermore, survival analysis showed that the median progression-free survival and median overall survival of patients in the ALB/PNI decreased group were significantly shorter than those of patients from the ALB/PNI increased group.

Conclusion

Anti-PD-1 immunotherapy might alter the nutritional and metabolic status in advanced HCC patients. We also should pay attention to the nutritional and metabolic status of patients when drug resistance is detected.

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Abbreviations

PD-1:

Programmed death-1

HCC:

Hepatocellular carcinoma

BMI:

Body mass index

AFP:

Alpha-fetoprotein

WBC:

White blood cell

N:

Neutrophil

L:

Lymphocyte

M:

Mononuclear

E:

Eosinophils

B:

Basophils

RBC:

Red blood cell

Hb:

Hemoglobin

PLT:

Platelet

TP:

Total protein

ALB:

Albumin

GLOB:

Globulin

A/G:

Albumin/globulin ratio

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AKP:

Alkaline phosphatase

TBA:

Total bile acid

TB:

Total bilirubin

DB:

Direct bilirubin

IB:

Indirect bilirubin

ADA:

Adenylate dehydrogenase

GGT:

γ-glutamyl transcriptase

Ccr:

Creatinine clearance rate

Cr:

Creatinine

BUN:

Urea nitrogen

UA:

Uric acid

LDH:

Lactate dehydrogenase

AFU:

α-L-fucosidase

GPDA:

Glycylproline dipeptidyl aminopeptidase

TG:

Triglyceride

TC:

Total cholesterol

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

VLDL:

Very low-density lipoprotein

GLU:

Glucose

K:

Potassium

Na:

Sodium

Cl:

Chloride

Ca:

Calcium

P:

Phosphorus

PNI:

Prognostic nutritional index

PLR:

Platelet-to-lymphocyte ratio

LMR:

Lymphocyte-to-monocyte ratio

NLR:

Neutrophil-to-lymphocyte ratio

PFS:

Progression-free survival

OS:

Overall survival

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Funding

This study was supported by the National Natural Science Foundation of China Youth Program (Grant Nos. 81802350 and 81802355), Science and Technology Major Project of China (Grant No. 2017ZX10203205), and Zhejiang provincial medical and health young talents project of China (Grant No. 2019RC285).

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Authors and Affiliations

  1. Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China

    Yizhen Jiang, Xiaoxuan Tu, Xiangying Zhang, Weiqin Jiang, Yi Zheng, Peng Zhao, Zhou Tong, Qihan Fu & Weijia Fang

  2. Department of Medical Oncology, Huzhou Central Hospital, Huzhou, 313000, Zhejiang, People’s Republic of China

    Yizhen Jiang, Haihong Liao, Shuwen Han, Quan Qi, Junjun Shen, Liping Zhong & Yuefen Pan

Authors
  1. Yizhen Jiang
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  2. Xiaoxuan Tu
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  3. Xiangying Zhang
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  4. Haihong Liao
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  5. Shuwen Han
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  6. Weiqin Jiang
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  7. Yi Zheng
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  8. Peng Zhao
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  9. Zhou Tong
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  10. Qihan Fu
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  11. Quan Qi
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  12. Junjun Shen
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  13. Liping Zhong
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  14. Yuefen Pan
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  15. Weijia Fang
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Contributions

The study was designed by Weijia Fang, Yuefen Pan, Yizhen Jiang, Xiaoxuan Tu, Xiangying Zhang, Weiqin Jiang, Yi Zheng, Peng Zhao, Zhou Tong, and Qihan Fu. Material preparation, data collection, and analysis were performed by Yizhen Jiang, Xiaoxuan Tu, Xiangying Zhang, Haihong Liao, and Shuwen Han. Yuefen Pan and Weijia Fang led the study. The first draft of the manuscript was written by Yizhen Jiang, Shuwen Han, Quan Qi, Junjun Shen, Liping Zhong, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yuefen Pan or Weijia Fang.

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Jiang, Y., Tu, X., Zhang, X. et al. Nutrition and metabolism status alteration in advanced hepatocellular carcinoma patients treated with anti-PD-1 immunotherapy. Support Care Cancer 28, 5569–5579 (2020). https://doi.org/10.1007/s00520-020-05478-x

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