Assessment of cardiac involvement of hepatitis C virus; tissue Doppler imaging and NTproBNP study

Hepatitis C disease burden is substantially increasing in Egyptian community, it is estimated that prevalence of Hepatitis C virus [HCV] in Egyptian community reach 22% of total population. Recently there is a global alert of HCV cardiovascular complications. To evaluate LV diastolic functions of HCV patients using tissue Doppler Imaging and NTPBNP. 30 HCV patients of 30 years, sex and BMI matched controls were evaluated by PCR, ECG, Echocardiography "conventional Doppler, pulsed wave tissue Doppler [PW-TD], strain rate imaging" and NTPBNP to assess LV diastolic functions. Mean age was 32.8 years +/- 5.1 in HCV group, 29.8 years +/- 6.6 in control group. Cardiovascular anomalies and predisposing factors were excluded. HCV group has shown significant increase in QTc interval, significant statistical increase in A wave, deceleration time; [p < 0.05], highly significant decrease in tissue Doppler E[a] [p < 0.001], highly significant decrease in A[a] [p < 0.001], highly significant increased E/E[a] ratio [p value < 0.001], significant decrease in E[a]/A[a] ratio and significant increase in SR[a] [p < 0.05]. NTPBNP levels showed highly significant increase with mean value 222 pg/ml +/- 283 in HCV group and 32.7 pg/ml +/- 21.2 in control group [p value < 0.001]. The best cut-off value of NTPBNP to detect diastolic dysfunction in HCV group was 213 pg/ml. No statistical differences in SRe/SRa and E/SRe ratios were observed, however they had significant correlation with NTPBNP level and tissue Doppler parameters. The best cut-off value of E/SRe ratio to detect diastolic dysfunction in HCV group was 0.91, with 75% sensitivity and 100% specificity. This data show the first direct evidence that HCV infection causes diastolic dysfunction without any other predisposing factors, probably due to chronic inflammatory reaction with mild fibrosis in the heart. Previous studies did not follow strict inclusion and exclusion criteria that confirm the independent role of HCV to cause diastolic dysfunction. Tissue Doppler was more sensitive to diagnose diastolic dysfunction than conventional Doppler

Promoter region polymorphism [174 G/C] of interleukin-6 gene and SLE; are they associated?

SLE is a systemic autoimmune disease with polyclonal B cell hyperactivity, spontaneous lymphocyte proliferation, and the production of pathogenic antibodies to self-antigens. Interleukin-6 is a pleiotropic cytokine with diverse functions including B-cell growth and differentiation. IL-6 levels have been shown to be affected by single nucleotide change from G to C at position -174 in the promoter region of the IL-6 gene.To find out whether single nucleotide polymorphisms in the promoter region of the IL-6 gene [-174 G/C] constitute a genetic susceptibility for SLE and its association with various disease clinical and immunological features. Forty-two female SLE patients and 40 healthy controls were genotyped for IL-6 gene promoter region [-174 G/C] polymorphism using PCR. SLE patients satisfied the 1982 revised criteria of the American Rheumatism Association for the classification of SLE, with a mean age of 32.4 +/- 5.5 years and mean disease duration of 5.7 +/- 1.5 years. The healthy controls were matched for age and sex, with a mean age of 31.7 +/- 4.9 years. All subjects were recruited from the Rheumatology and Rehabilitation and Internal Medicine Departments, Kasr El Aini Hospitals. SLE clinical and laboratory features were recorded including constitutional, hematological, joint, renal, and neuropsychiatric manifestations, oral ulcers, serositis, malar rash, and photosensitivity and CBC, liver, kidney functions and serum C3 and C4 levels. Positivity for ANAs, Anti-dsDNA and Anti-Sm antibodies were determined. Genotypic and allelic distributions showed no significant differences between SLE patients and controls. The frequency of G allele was higher than C allele in both patients [83.3% vs. 16.7%] and controls [85% vs. 15%]. SLE patients with GG genotype showed significantly higher frequencies and increased risk of; constitutional manifestations at disease onset [P = 0.02], OR [95% CI] = 6.55 [1.22-35.12], photosensitivity [P = 0.03], OR [95% CI] = 4.67 [1.11-19.54], hematological disorders [P = 0.02], OR [95% CI] = 5.5 [1.29-23.39] and positivity of ANAs and Anti-dsDNA [P = 0.046, 0.03: OR [95% CI] = 7 [1.1-45.44], 6.43 [1.23-33.65], respectively]. Furthermore, those patients had significantly lower mean WBCs counts when compared to SLE patients with [GC and CC] genotypes [4.54 +/- 1.31 vs. 5.98 +/- 1.04/dl, P = 0.002]. Twenty-five patients had lupus nephritis [LN] proved by renal biopsy but none of them had CC genotype. LN patients with GG genotype had nearly similar mean 24-h proteinuria to those with GC genotype [2.93 +/- 1.07 vs. 2.68 +/- 1.06 g/24 h and P = 0.39]. No significant difference was found in IL-6 genotype and allele distributions when patients with diffuse proliferative glomerulonephritis [class IV], which has the worst prognostic outcome, were compared to patients with non-class IV glomerulonephritis [classes II and III] [P = 0.12, 0.15, respectively]. IL-6 promoter region [-174 G/C] polymorphism does not confer susceptibility to SLE but it is related to the presence of distinct clinical and immunological features. Furthermore, the increased frequency of the high-response G allele suggests that a genetically determined high IL-6 response may have a pathogenic role

Genetic polymorphism of uridine-diphosphoglucuronosyl transferase 1A7 gene in chronic viral hepatitis and hepatocellular carcinoma

Hepatocellular Carcinoma [HCC] is the most common cause of primary liver neoplasm and the fourth most frequent type of cancer worldwide causing one million deaths per year. Genetic polymorphisms of UDP-glucuronosyltransferases [UGTs], which detoxifies endogenous and environmental carcinogen, have been reported to be associated with HCC. The present study aimed to elucidate the role of UGT1A7 SNP [622 T-C] in the pathogenesis of Hepatocellular Carcinoma [HCC] and whether this polymorphism is associated with elevated bilirubin level or not. This study was conducted on 22 patients with HCC, 25 patients with chronic viral hepatitis B and/ or C and 16 apparently healthy controls. All subjects underwent laboratory tests for Liver and Kidney functions, serological markers [HBV and HCV] and serum AFP as a tumor marker, Genomic DNA from the blood was analyzed for UGT1A7 polymorphism using PCR-RFLP. The prevalence of HCV infection was higher in HCC group compared to other groups. AFP-level significantly increased in HCC than in viral hepatitis and control [p<0.0005]. A statistically significant increase was found in the frequency of risky genotypes [TC, CC] in HCC group as compared to the protective genotype [TT] [P<0.01]. UGT1A7 T allele and C allele were designated as H [high activity] and L [low activity] alleles, respectively. A statistically significant increase was found in frequency of L allele in HCC group [54%] as compared to control group [25%] p=0.03. On the other hand, the H allele showed statistically significant decrease in HCC group [46%] compared to control group [75%] p=0.03. Increase in total bilirubin level in cases harboring UGT 1A7 Polymorphism compared to wild genotype [p<0.01] was observed demonstrating its role in the pathogenesis of hyperbilirubineamia. The UGT1A7 polymorphism was associated with elevated bilirubin level and may play a role in the pathogenesis of HCC