Immunohistochemical evaluation of oxidative stress markers in chronic hepatitis C.
Oxidative stress (OS) plays a major role in chronic hepatitis C. Various OS markers have been found to be elevated in hepatitis C virus (HCV)-related liver disease. This study detected the presence of OS in serum and liver biopsy specimens of HCV patients. Reactive oxygen molecules (ROM) in sera of 54 HCV patients were compared with 23 controls. OS markers 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal, malondialdehyde, and thioredoxin were measured in liver biopsy specimens of 18 HCV patients with fibrosis staging F1 (six); F2 (two), F3 (four), and F4 (six). The interferon (IFN) response and hepatocellular carcinoma (HCC) occurrence in the presence of OS markers were also evaluated. The level of ROM in HCV patients was 318 +/- 56.7 Carr compared with 248 +/- 40.8 Carr in controls (p=0.032). Multivariate analysis found age (p=0.0236) to be the only independent variable associated with increase in ROM in sera. In liver biopsy specimens, OS markers were found mainly around the area of piecemeal necrosis or the periportal area. The presence of OS markers seemed to increase with fibrosis staging, although not significantly. The OS DNA damage marker 8-OHdG was detected in the nucleus of hepatocytes. Thirteen patients received IFN therapy. During the 4-year follow-up period, HCC developed in four nonresponders to IFN and in one untreated patient. OS markers were stained in both HCC cells and non-HCC cells in HCC patients. OS markers were found in serum and liver specimens of HCV-associated liver disease and in HCC tissue. Detection of OS markers may be important for monitoring disease progression in HCV patients. Antioxidant therapy in combination with antiviral therapy may minimize liver damage and aid in the prevention and subsequent development of HCC.
Mahmood
Sabina
S
Department of Internal Medicine, Center for Liver Diseases, Kawasaki Hospital, Kawasaki Medical School, Okayama 700-0986, Japan. sabina@m4.dion.ne.jp
Kawanaka
Miwa
M
Kamei
Ayumi
A
Izumi
Akiyoshi
A
Nakata
Keiichi
K
Niiyama
Gouichi
G
Ikeda
Hideji
H
Hanano
Shinichi
S
Suehiro
Mitsuhiko
M
Togawa
Kazumi
K
Yamada
Gotaro
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D000447:Aldehydes / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000097:blood; D013879:Thioredoxins / Q000032:analysis
D000447:Aldehydes; D015415:Biomarkers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal