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

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.