Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C

Autor: Nobuyuki Baba, Kazuhide Yamamoto, Tetsuya Yasunaka, Yasuto Takeuchi, Kazuhiro Nouso, Fusao Ikeda, Shintaro Nanba, Yoshiaki Iwasaki, Takuya Nagano, Yuki Moritou, Hideki Ohnishi, Yasuhiro Miyake, Akinobu Takaki, Koichi Takaguchi, Tomonori Senoh, Hiroyuki Seki
Rok vydání: 2015
Předmět:
Male
0301 basic medicine
Iron metabolism disorder
Time Factors
medicine.disease_cause
Severity of Illness Index
Gastroenterology
Polyethylene Glycols
0302 clinical medicine
Risk Factors
Pegylated interferon
Odds Ratio
biology
Liver Neoplasms
General Medicine
Hepatitis C
Middle Aged
Recombinant Proteins
Treatment Outcome
Liver
8-Hydroxy-2'-Deoxyguanosine
Disease Progression
Drug Therapy
Combination
Female
030211 gastroenterology & hepatology
medicine.drug
medicine.medical_specialty
Carcinoma
Hepatocellular
Alpha interferon
Antiviral Agents
Pathology and Forensic Medicine
03 medical and health sciences
Hepcidin
Internal medicine
Ribavirin
medicine
Humans
Aged
Proportional Hazards Models
Hepatitis
business.industry
Deoxyguanosine
Interferon-alpha
Hepatitis C
Chronic
medicine.disease
Iron Metabolism Disorders
Ferritin
Oxidative Stress
Logistic Models
030104 developmental biology
Multivariate Analysis
Immunology
Leukocytes
Mononuclear
biology.protein
business
Biomarkers
Oxidative stress
Follow-Up Studies
Zdroj: Journal of Clinical Pathology. 69:226-233
ISSN: 1472-4146
0021-9746
Popis: Oxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC) after interferon therapy has not been established.We investigated the impact of oxidative stress and iron deposition on HCC development after therapy with pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and intracellular iron homeostasis was evaluated in liver tissues, peripheral blood mononuclear cells and sera.Of 203 patients enrolled, 13 developed HCC during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were significantly associated with HCC development in multivariate analysis (p=0.0012) which was also significantly correlated with severity of hepatic iron deposition before therapy (p0.0001). Systemic and intracellular iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5) expression levels were significantly suppressed in CHC patients (p=0.0032 and p=0.016, respectively) despite their significantly higher levels of serum iron and ferritin compared with controls. However, intracellular iron regulators of FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron deposition. Significant correlations were observed among IL-6, bone morphogenetic protein 6, hepcidin and ferroportin, as regards systemic iron regulation.Measurement of hepatic oxidative stress before antiviral therapy is useful for the prediction of HCC development after interferon therapy. Low baseline levels of the intracellular iron regulators of FBXL5 in addition to a suppressed hepcidin level might be associated with severe hepatic iron deposition in CHC patients.UMIN 000001031.
Databáze: OpenAIRE
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