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.
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.