Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C.
BACKGROUND
New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC).


METHODS
Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay.


RESULTS
The serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens.


CONCLUSIONS
DHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC.
Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco ; Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan ; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Sayeh
S
Ezzikouri
Division of Hepatology, The Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
Kiminori
K
Kimura
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
Hajime
H
Sunagozaka
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
Shuichi
S
Kaneko
Department of Gastroenterology, Showa University, Fujigaoka Hospital, Kanagawa, Japan.
Kazuaki
K
Inoue
Chemo-Sero Research Institute, Kyoku-shi, Kumamoto, Japan.
Tomohiro
T
Nishimura
Division of Pathology, The Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
Tsunekazu
T
Hishima
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Japan.
Michinori
M
Kohara
Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan ; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Kyoko
K
Tsukiyama-Kohara
D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000473:pathology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000276:immunology*; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D001323:Autoantibodies; D015415:Biomarkers; D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human
3β-Hydroxysterol Δ24-reductase antibody; Biomarker; Hepatitis C virus; Liver cancer; Serum autoantibody