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Volume 76 - 2013 - Fasc.4 - Original articles

Interferon mono-therapy for symptomatic HCV-associated mixed cryoglobuline- mia : meta-analysis of clinical studies

Objective : Mixed cryoglobulinemia (MC) is an important com- plication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC ; some information exists on IFN mono-therapy for symptomatic HCV- MC in the non-transplant setting, but its efficacy is still unclear. Methods : We evaluated efficacy and safety of mono-therapy with standard or pegylated interferon (IFN) for symptomatic HCV-associated MC in non-immunosuppressed individuals by performing a systematic review of the literature with a meta- analysis of clinical studies. We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The primary outcome was sustained viral response (SVR, as a measure of efficacy), and the secondary outcome was the drop-out rate due to side-effects (as a measure of tolerability). Results : We identified eleven clinical studies (n = 235 unique patients) ; the rate of baseline kidney involvement ranged between 11% and 74%. The summary estimate of frequency of sustained viral response was 0.15 with a 95% Confidence Interval (CI) of 0.08 ; 0.22 (random-effects model). Significant heterogeneity occurred (P = 0.001 ; Chi2 = 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stop- ping antiviral agents was 3.4% ; most patients experienced minor side effects which did not require interruption of therapy. Baseline cirrhosis (P < 0.04), kidney involvement (P < 0.07), and arthralgias (P < 0.04) showed negative impact on viral response. We found an excellent relationship between viral and clinical response [weighted K = 0.72 (95% CI, 0.54 ; 0.89)], by an evaluation at individual level on a subset of reports (n = 65 unique patients). Conclusions : This meta-analysis of clinical studies shows that antiviral therapy with standard or pegylated IFN alone for symp- tomatic MC associated with HCV gives satisfactory response in a minority of patients only. Clinical trials based on combination therapy (pegylated interferon plus ribavirin) or novel immuno- suppressive agents are under way in order to improve efficacy and safety of symptomatic HCV-MC. (Acta gastroenterol. belg., 2013, 76, 363-371).


Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9

Background and aim : At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study. Methods : We first examined the different expression of cas- pase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was estab- lished in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. Results : Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P < 0.05). In addition, the down-regula- tion of caspase-9 expression is more common in poorly differenti- ated cancers (P < 0.05). Concerning cell lines, overexpression cell groups showed higher expression of caspase-9, poorer colony for- mation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and G0/G1 arrest, while up-regulating the expression of caspase-3 (P<0.05). Interestingly, down-regulation of carcinoembryonic antigen secretion was also observed in caspase-9 overexpression cells (P < 0.05). Conclusion : The change of caspase-9 expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied. (Acta gastroenterol. belg., 2013, 76, 372-380).


Prevalence of and risk factors for H. pylori infection in healthy children and young adults in Belgium anno 2010-2011

Objective : Estimation of prevalence and risk factors for Helico- bacter pylori (H. pylori) infection in children and young adults in Belgium. Study design : Five hundred and sixteen schoolchildren between 12 and 25 years old were tested for H. pylori infection using 13C- UBT in different regions in Belgium. A questionnaire was used to evaluate risk factors. Results : Fifty six (11%) tested positive. In children born in Belgium, with parents from Belgium, 13 (3,2%) tested positive. In children born in a foreign country, 20 (60%) tested positive ; if born in Belgium but 1 or 2 parents were from a foreign country, 15 (30%) tested positive. Differences were significant (p < 0.001). In the multivariate analyses, significant risk factors were staying in a day nursery, a birthplace of child or father outside Belgium, and lower education levels of mother. Conclusion : In this cohort of Belgian asymptomatic children and young adults, the prevalence of H. pylori infection is 11%, ranging from 3,2% in Belgian born children with Belgian parents to 60% in children born in high prevalence countries from foreign parents. The most significant risk factor found in this study was origin. (Acta gastroenterol. belg., 2013, 76, 381-385).


MicroRNA Expression Profiles of Circulating Microvesicles in Hepatocellular Carcinoma

Background : Microvesicles (MVs) packaged with microribonu- cleic acids (miRNAs) have been shown to be released mainly from tumor cells. However, little information is known for miRNAs from MVs in hepatocellular carcinoma (HCC). Hence, we explored the MVs' miRNAs expression profiles in HCC. Methods : MVs were collected from peripheral blood of HCC, chronic hepatitis B (CHB) and normal controls. miRNA from MVs were labeled and analyzed by Agilent miRNA microarry. Bioinfor- matics tools were used to analyze function of the differentially expressed MVs' miRNAs. Results : A total of 242 aberrantly expressed miRNAs were iden- tified in HCC-MVs compared with CHB-MVs and the control. Among them, 115 miRNAs were over-expressed with up to 31 fold difference (miR-671-5p) and 127 were down-expressed with up to 0.041 fold difference (miR-432) in HCC. By software miRror2.0, nucleolar protein 3 (NOL3) was found to be the core player among 300 target genes of top ten up-regulated miRNAs and serine/ arginine repetitive matrix 1(SRRM1) was central among the 219 targets of the top ten down-regulated miRNAs. We also analyzed GO categories for these predicted genes : cellular component, bio- logical processes, and molecular function. The deregulation of MVs' miRNAs and their target genes were closely involved in the pathways of HCC. Conclusions : Our study firstly demonstrated that miRNAs were differentially expressed in HCC-MVs compared with CHB and normal controls. Aberrant HCC-MVs miRNAs may play impor- tant roles in the development of HCC. (Acta gastroenterol. belg., 2013, 76, 386-392).