首页|Decreased mitochondrial deoxyribonucleic acid and increased oxidative damage in chronic hepatitis C

Decreased mitochondrial deoxyribonucleic acid and increased oxidative damage in chronic hepatitis C

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AIM:To determine whether alteration of the mitochondria DNA (mtDNA) copy number and its oxidative damage index (mtDNA△CT) can be detected by analysis of peripheral blood cells in hepatitis C virus (HCV)-infected patients.METHODS:This study enrolled two groups of patients aged 40-60 years:a control group and an HCV-infected group in Department of Gastroenterology and Hepatology in Changhua Christian Hospital.Patients with co-infection with hepatitis B virus or human immunodeficiency virus,autoimmune disease,malignant neoplasia,pregnancy,thyroid disease,or alcohol consumption > 40 g/d were excluded.HCV-infected patients who met the following criteria were included:(1)positive HCV antibodies for > 6 mo; (2) alanine aminotransferase (ALT) levels more than twice the upper limit of normal on at least two occasions during the past 6 mo; and (3) histological fibrosis stage higher than F1.The mtDNA copy number and oxidative damage index of HCV mtDNA (mtDNA△CT) were measured in peripheral blood leukocytes.The association between mtDNA copy number and mtDNA△Cr was further analyzed using clinical data.RESULTS:Forty-seven normal controls (male/female:26/21,mean age 50.51 ± 6.15 years) and 132 HCV-infected patients (male/female:76/61,mean age 51.65± 5.50 years) were included in the study.The genotypes of HCV-infected patients include type 1a (n =3),type 1b (n =83),type 2a (n =32),and type 2b (n =14).Liver fibrosis stages were distributed as follows:F1/F2/F3/F4 =1/61/45/25 and activity scores were A0/A1/A2/A3 =7/45/55/25.There were no age or genderdifferences between the two groups.HCV-infected patients had higher hepatitis activity (aspartate transaminase levels 108.77 ± 60.73 vs 23.19 ± 5.47,P < 0.01;ALT levels 168.69 ± 93.12 vs 23.15 ± 9.45,P < 0.01)and lower platelet count (170.40 ± 58.00 vs 251.24 ±63.42,P < 0.01) than controls.The mtDNA copy number was lower in HCV-infected patients than in controls (173.49 vs 247.93,P < 0.05).The mtDNA△CT was higher in HCV-infected patients than in controls (2.92 vs 0.64,P < 0.05).To clarify the clinical significance of these results in HCV-infected patients,their association with different clinical parameters among HCV-infected patients was analyzed.A negative association was found between mtDNA copy number and elevated aspartate transaminase levels (r =-0.17,P < 0.05).Changes in mtDNA copy number were not associated with HCV RNA levels,HCV genotypes,liver fibrosis severity,or inflammatory activity in the liver biopsy specimen.However,a correlation was observed between mtDNA△Cr and platelet count (r =-0.22,P < 0.01),HCV RNA level (r =0.36,P < 0.01),and hepatitis activity (r =0.20,P =0.02).However,no difference in the change in mtDNA△Crwas observed between different fibrosis stages or HCV CONCLUSION:Oxidative stress and mtDNA damage are detectable in patient's peripheral leukocytes.Increased leukocyte mtDNA△CT correlates with higher HCV viremia,increased hepatitis activity,and lower platelet count.

Hepatitis CMitochondriaOxidative stressMitochondrial DNABiomarker

Hsu-Heng Yen、Kai-Lun Shih、Ta-Tsung Lin、Wei-Wen Su、Maw-Soan Soon、Chin-San Liu

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Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500, Taiwan, China

Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua 500, Taiwan,China

Changhua Christian Hospital

99-CCH-IPR-12

2012

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子:1.001
ISSN:1007-9327
年,卷(期):2012.18(36)
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