Circulating micro RNA, mi R-122 and mi R-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma

AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-na?ve chronic hepatitis C(CH)(n = 30), post-hepatitis C compensated cirrhosis(LC)(n = 30) and treatment-naive HCC(n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miR NA expression by RT-PCR.RESULTS: There was a significant fold change in serum mi RNA expression in the different patient groups when compared to normal controls; mi R-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, mi R-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group(P = 0.01). Comparing fold changes in miR NAs in HCC group vs non HCC group(CH and Cirrhosis), there was non-significant fold elevation in miR-122(P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC(P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.

Glutathione peroxidase, superoxide dismutase and catalase activities in children with chronic hepatitis

The advantages of measuring hepatic oxidative status in liver biopsy are that it helps in diagnosis of hepatic dysfunction, reflects the degree of deterioration in the liver tissues, and helps to determine the severity of hepatic injury. We aimed to study the oxidative stress state in children with chronic hepatitis by using indirect approach in which antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) are determined in the liver tissue. The present study included 21 children and adolescents (12 males, 9 females) suffering from chronic hepatitis. Patients were selected from the Hepatology Clinic, New Children’s Hospital, Cairo University from November 2006 till 2009 and compared with a group of 7 children who happened to have incidental normal liver biopsy. Children with chronic hepatitis had mean age 8.12 ± 1.15 years. It was further subdivided into 2 subgroups: chronic viral heaptitis (n = 13) and cryptogenic hepatitis (n = 8). GPX, SOD and CAT levels were measured in fresh liver tissue (cell free homogenates) using ELISA. In chronic hepatitis group;there was a significant increase in the hepatic GPX activity (38.59 ± 35.82 nmol/min/ml) as compared to the control group (10.62 ± 6.68 nmol/min/ml). Also a significant correlation was observed between SOD and both ALT (r = 0.87, p < 0.05) and AST (r = 0.74, p < 0.05). GPX correlated with ALT (r = 0.80, p < 0.05) level in the chronic viral hepatitis subgroup. Our findings suggest that oxidative stress could play a role in the pathogenesis of chronic hepatitis. These preliminary results are encouraging to conduct more extensive clinical studies combining antioxidant therapy with various treatments.

Targeting Transforming Growth Factor-<i>β</i>(TGF-<i>β</i>) in Cancer and Non-Neoplastic Diseases

Transforming growth factor-β?(TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost three decades ago, there have been tremendous advances in our understanding of its complex biology. TGF-β?misregulation has been implicated in the pathogenesis of a variety of diseases, including cancer with a direct role in facilitating metastasis, fibrosis and inflammation. Consequently, TGF-β?is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis;and it offers an attractive target for cancer therapy. Several anti-TGF-β?approaches, such as TGF-β?antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-β?type 1 receptor kinase, have shown great promise in the preclinical studies. Here, we consider why the TGF-βsignaling pathway is a drug target, the potential clinical applications of TGF-β?inhibition, the issues arising with anti-TGF-β?therapy and how these might be adopted using personalized approaches with a special care for patient selection and timing of therapy so that we may bring forward all the potentials of targeting this pathway for therapeutic uses in both cancer, preferentially in combination therapy, and non-neoplastic diseases.

Prevalence of occult hepatitis C in egyptian patients with non alcoholic fatty liver disease

This study aim is to assess the prevalence of occult HCV infection among Egyptian patients with non alcoholic fatty liver disease (NAFLD) with elevated AST and ALT, and to correlate presence of occult HCV with severity of liver disease. Patients and Methods: After informed consent 27 patients with elevateed liver enzymes diagnosed as NAFLD were examined for demographic, clinical, laboratory data and Ultrasonography. Liver biopsy was done and tested for HCV RNA in tissue. Genotyping using RFLP analysis of PCR products in the 5’NCR was done for positive cases. Results: HCV RNA in tissue was positive in 11/27 patients (40.7%);genotype was 4a in all positive cases. AST and ALT values showed significantly lower values in occult HCV than the non HCV NAFLD group. Liver biopsy of studied patients showed no significant difference as regard inflammation and fibrosis according to METAVIR score. Conclusions: Occult HCV is highly prevalent among Egyptian NAFLD patients. It seems to induce a mild liver disease. Patients with elevated ALT and negative HCV RNA in sera might be investigated for tissue HCV RNA. Follow up is recommended for the occult HCV patients to monitor progression to overt disease.

HIV Prevalence among HCV Egyptian Infected Patients and Its Impact on the Result of HCV Treatment

Background and Aim of the Study: HCV infection is the most common co-infection in HIV patients so we aimed to determine the prevalence of HIV infection in chronic HCV patients and its impact on chronic HCV patients treatment response. Patients and Methods: A retrospective study performed on 1852 chronic HCV patients subjected to anti HCV treatment with alpha 2a, alpha 2b or standard interferon and Ribavirin and tested and confirmed for HIV co infection by ELISA twice. Upon HIV testing, two groups were generated, Group 1: 1840 HCV patients, positive for HCV RNA, and Group 2: 12 HIV positive patients and positive also for HCV. Informed consents were obtained from patients. Proper hematological biochemical investigations and other causes of hepatitis rather than HCV were carried out and excluded. Results: The prevalence of HIV among HCV infected Egyptian patients was 0.64%. We found a male gender predominance;the hematological and biochemical parameters were similar in both groups with mild elevations in liver enzymes in group II. High rates of failure to treatment (77.8%) with lower SVR (22.2%) were in group II compared to group I (59.9%) as SVR was 22.1% in group II vs. 34.1% in group I, however with no statistical significance. Conclusion: Despite the lower prevalence of HIV in Egyptian patients with HCV infection, it still affects their response to treatment .Therefore;we must screen HIV in all HCV patients and recommend its test to routine investigations before starting HCV therapy.