title: Decreased mitochondrial deoxyribonucleic acid and increased oxidative damage in chronic hepatitis C.
abstract: OBJECTIVE
  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(∆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 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500, Taiwan, China. 91646@cch.org.tw
authors.forename: Hsu-Heng
authors.initials: HH
authors.lastname: Yen
authors.forename: Kai-Lun
authors.initials: KL
authors.lastname: Shih
authors.forename: Ta-Tsung
authors.initials: TT
authors.lastname: Lin
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Su
authors.forename: Maw-Soan
authors.initials: MS
authors.lastname: Soon
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012367:RNA, Viral / Q000097:blood
chemical_list: D004272:DNA, Mitochondrial; D012367:RNA, Viral; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine