Mitochondrial DNA copy number in Hepatitis C virus-related chronic liver disease: impact of direct-acting antiviral therapy.

Hepatitis C virus (HCV) infection can regulate the number and dynamics of mitochondria, and is associated with a prominent hepatic mitochondrial injury. Mitochondrial distress conveys oxidative damage which is implicated in liver disease progression. The present study was conducted to assess the change of mitochondrial DNA (mtDNA) copy number in patients with HCV-related chronic liver disease and the impact of direct-acting antiviral (DAA) therapy. Whole blood mtDNA copy number was measured using real-time quantitative polymerase chain reaction at baseline and 12 weeks after the end of therapy in 50 treatment-naïve HCV-infected patients who achieved sustained viral response (SVR) after DAA therapy and 20 healthy controls. Whole blood mtDNA copy number appeared significantly lower in HCV-infected patients before therapy compared to healthy subjects (P < 0.001). Post-treatment, there was significant increase of mtDNA copy number in HCV-infected patients at SVR12 compared to the pre-treatment values (P < 0.001), meanwhile it didn't differ significantly between HCV-infected patients after therapy and healthy subjects (P = 0.059). Whole blood mtDNA copy number correlated inversely to the serum bilirubin in HCV-infected patients (P = 0.013), however it didn't correlate significantly to the serum aminotransferases, viral load or fibrosis-4 score (P > 0.05). In conclusion, chronic HCV infection has been associated with a prominent mitochondrial injury which could mediate a progressive liver disease. The improved mtDNA content after DAA therapy highlights a possible potential of these drugs to alleviate mitochondrial damage in HCV-related liver disease.

Serum and ascitic D-dimer in cirrhotic patients with spontaneous bacterial peritonitis.

AIM OF THE STUDY: The study aimed to investigate serum and ascitic fluid D-dimer level in patients with liver cirrhosis with and without ascites and to evaluate the impact of spontaneous bacterial peritonitis (SBP) on circulating serum and ascitic fluid D-dimer levels. MATERIAL AND METHODS: This study was conducted on 60 subjects who were further subdivided into group I comprising 15 patients with liver cirrhosis and no ascites, group II comprising 15 cirrhotic patients with ascites, group III comprising 15 cirrhotic patients with ascites and SBP, and group IV comprising 15 healthy controls. All patients were subjected to full history taking, physical examination, laboratory investigations, and measurement of serum D-dimer in all groups and ascitic fluid D-dimer in groups II and III. The diagnostic performance of serum D-dimer was tested to detect SBP. RESULTS: Serum D-dimer differed significantly between groups III and IV, whilst no significant differences were detected between the other groups and group IV. Moreover, group III showed a significantly higher level of serum D-dimer. Ascitic fluid D-dimer mean levels showed no statistically significant differences. A statistically significant positive correlation was found between serum D-dimer level and ascitic fluid D-dimer in group III, r = 0.682. Using a sensitivity and specificity level of 80%, a cut-off value (COV) of > 323.2 ng/ml could differentiate between patients with SBP and patients with ascites only. CONCLUSIONS: Serum D-dimer significantly correlated with ascitic fluid D-dimer in patients with SBP, whereas no significant correlation was found in patients with cirrhotic ascites without bacterial infection. D-dimer showed good diagnostic performance for SBP among patients with liver cirrhosis.

Comparison of hepatic and splenic stiffness in chronic hepatitis C infection with and without schistosomal infection; correlation with hepatic histopathological changes.

AIM OF THE STUDY: To assess the degree of liver and spleen stiffness in chronic hepatitis C virus (HCV) patients co-infected with schistosomiasis, and chronic HCV mono-infected patients. MATERIAL AND METHODS: The present study was conducted on 50 Egyptian chronic HCV patients, categorized into two groups: group A (25 patients with chronic HCV mono-infection) and group B (25 patients with chronic HCV and schistosomiasis coinfection). Also, 25 age- and sex-matched healthy subjects with no evidence of liver disease were included in the study as a control group. Stage of fibrosis was assessed invasively by histopathological examination of liver biopsies (patients only) and non-invasively by acoustic radiation force impulse imaging (ARFI) (all subjects). RESULTS: ARFI of liver (ARFI L) and ARFI of spleen (ARFI S) in group A patients who had significant fibrosis were 1.82 ±0.24 and 2.72 ±0.26, respectively, while in group B, ARFI L and ARFI S in patients with significant fibrosis was 1.99 ±0.53 and 3.10 ±0.57, respectively. CONCLUSIONS: The current study demonstrated insignificantly higher values of liver stiffness and significantly higher values of spleen stiffness assessed by ARFI in patients co-infected with HCV and schistosomiasis than mono-infected with HCV.

Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis.

BACKGROUND: Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. OBJECTIVE: This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. PATIENTS AND METHODS: This study included 24 patients with HCV-related cirrhosis, Child-Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. RESULTS: DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. CONCLUSION: Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.

Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma.

AIM: To assess the use of mitochondrial DNA (mtDNA) content as a noninvasive molecular biomarker in hepatitis C virus-related hepatocellular carcinoma (HCV-HCC). MATERIALS AND METHODS: A total of 135 participants were enrolled in the study. Equal numbers of subjects were enrolled in each of three clinically defined groups: those with HCV-related cirrhosis (HCV-cirrhosis), those with HCV-HCC, and a control group of age- and sex-matched healthy volunteers with no evidence of liver disease. mtDNA concentrations were determined using a quantitative real-time polymerase chain reaction (PCR) technique. RESULTS: mtDNA content was lowest among the HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multicentric hepatic lesions had significantly lower mtDNA content than HCC patients with less advanced disease. When a receiver operating characteristic curve analysis was used, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA content was associated with HCC risk when using either or both healthy controls and HCV-cirrhosis groups for reference. CONCLUSIONS: mtDNA content analysis could serve as a noninvasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the nonsignificant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the gray zone created by the use of alpha-fetoprotein in some cirrhotic patients.