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

Abstract

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.