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


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.
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Choong-Kyun
CK
Noh
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Soon Sun
SS
Kim
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Dong-Kyu
DK
Kim
Clinical Trial Center, Ajou University Hospital, Suwon, Republic of Korea.
Hyun-Young
HY
Lee
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Hyo Jung
HJ
Cho
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
So Young
SY
Yoon
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Gil Ho
GH
Lee
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Sun A
SA
Hyun
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Yu Jeong
YJ
Kim
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Ho Joong
HJ
Kim
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Joo An
JA
Hwang
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Seun Joo
SJ
Ahn
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Sung Jae
SJ
Shin
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Kee Myung
KM
Lee
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Byung Moo
BM
Yoo
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
Sung Won
SW
Cho
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: jaeyoun620@gmail.com.
Jae Youn
JY
Cheong
D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000097:blood*
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; D053491:Proteinase Inhibitory Proteins, Secretory
Diagnosis; Hepatitis B; Hepatocellular carcinoma; Inter-alpha-trypsin inhibitor heavy chain H4; Survival