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

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.

Risk factors and prediction score for chronic pancreatitis: A nationwide population-based cohort study

AIM To explore the risk factors of developing chronic pancreatitis(CP) in patients with acute pancreatitis(AP) and develop a prediction score for CP.METHODS Using the National Health Insurance Research Database in Taiwan, we obtained large, population-based data of 5971 eligible patients diagnosed with AP from 2000 to 2013. After excluding patients with obstructive pancreatitis and biliary pancreatitis and those with a follow-up period of less than 1 year, we conducted a multivariate analysis using the data of 3739 patients to identify the risk factors of CP and subsequently develop a scoring system that could predict the development of CP in patients with AP. In addition, we validated the scoring system using a validation cohort.RESULTS Among the study subjects, 142 patients(12.98%) devel-oped CP among patients with RAP. On the other hand, only 32 patients(1.21%) developed CP among patients with only one episode of AP. The multivariate analysis revealed that the presence of recurrent AP(RAP), alcoholism, smoking habit, and age of onset of < 55 years were the four important risk factors for CP. We developed a scoring system(risk score 1 and risk score 2) from the derivation cohort by classifying the patients into low-risk, moderate-risk, and high-risk categories based on similar magnitudes of hazard and validated the performance using another validation cohort. Using the prediction score model, the area under the curve(AUC) [95% confidence interval(CI)] in predicting the 5-year CP incidence in risk score 1(without the number of AP episodes) was 0.83(0.79, 0.87), whereas the AUC(95%CI) in risk score 2(including the number of AP episodes) was 0.84(0.80, 0.88). This result demonstrated that the risk score 2 has somewhat better prediction performance than risk score 1. However, both of them had similar performance between the derivation and validation cohorts.CONCLUSION In the study,we identified the risk factors of CP and developed a prediction score model for CP.