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B형 간염 관련 간암 환자에서 진단 및 예후 예측 인자로서 Inter-alpha-trypsin inhibitor heavy chain H4에 대한 연구

Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma

초록/요약

Objectives: Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC). Design and Methods: The study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU). Results: ITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P <0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (>5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P = 0.017). A Kaplan-Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (<80 DU) and a large tumor size compared to that among other HCC patients (P <0.001), and among patients with high AFP (>200 ng/mL) and low ITIH4 compared to that among other HCC patients (P = 0.041). Conclusions: Serum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.

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목차

ABSTRACT ⅰ
TABLE OF CONTENTS iii
LIST OF FIGURES iv
LIST OF TABLES v
Ⅰ. INTRODUCTION 1
Ⅱ. PATIENTS AND METHODS 3
A. Patients and serum samples 3
B. Western blot analysis 3
C. Statistical analysis 4
Ⅲ. RESULTS 5
A. Selection of candidate biomarker for HBV-associated HCC 5
B. Diagnostic value of ITIH4 for the detection of HCC 6
C. Identification of factors that predict survival in patients with HCC 7
D. Prognostic significance of ITIH4 in patients with HCC 8
Ⅳ. DISCUSSION 13
Ⅴ. CONCLUSION 16
REFERENCES 17
국문 요약 20

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