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

摘要

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 HCVinfected 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 CT was further analyzed using clinical data.RESULTS:Forty-seven normal controls(male/female:26/21,mean age 50.51 ± 6.15 years) and 132 HCVinfected 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 gender differences 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 CT 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 CT was observed between different fibrosis stages or HCV genotypes.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.