The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major health problem worldwide. The DNA PM of cancer-related genes plays an important role in the development and progression of HCC. The data reported in our studies provide evidence that PM of p73, p14, and O6-MGMT is associated with HCC, whereas PM of the APC gene is more common in chronic hepatitis (CH) cases. Thus, it could be used as a maker for early detection of HCV-induced chronic active hepatitis. A panel of four genes APC, p73, p14, and O6-MGMT independently affected the classification of cases into HCC and CH with accuracy (89.9%), sensitivity (83.9%), and specificity (94.7%). Also, the detection of PM of APC, FHIT, p15, p16, and E-cadherin in peripheral blood of HCV-infected patients is a highly sensitive and specific. Therefore, blood could be used as efficiently as tissue biopsies to assess PM of different genes. This could help in the follow-up of CH patients and early detection of HCC. We did not observe a significant difference in the methylation status according to the virus type HBV versus HCV. So, plasma DNA is a reliable resource for methylation studies in the future, irrespective of the type of hepatitis infection

Prevalence, Awareness, Treatment, and Control of Hypertension among Saudi Adult Population: A National Survey

This cross-sectional study aimed at estimating prevalence, awareness, treatment, control, and predictors of hypertension among Saudi adult population. Multistage stratified sampling was used to select 4758 adult participants. Three blood pressure measurements using an automatic sphygmomanometer, sociodemographics, and antihypertensive modalities were obtained. The overall prevalence of hypertension was 25.5%. Only 44.7% of hypertensives were aware, 71.8% of them received pharmacotherapy, and only 37.0% were controlled. Awareness was significantly associated with gender, age, geographical location, occupation, and comorbidity. Applying drug treatment was significantly more among older patients, but control was significantly higher among younger patients and patients with higher level of physical activity. Significant predictors of hypertension included male gender, urbanization, low education, low physical activity, obesity, diabetes, and hypercholesterolemia. In conclusion prevalence is high, but awareness, treatment, and control levels are low indicating a need to develop a national program for prevention, early detection, and control of hypertension

Haematological, lipid profile and other biochemical parameters in normal and hypertensive subjects among the population of the eastern province of Saudi Arabia

Objective: To determine the lipid profile complete blood count and other biochemical parameters in normotensive and hypertensive individuals. Design: Cross-sectional population-based epidemiological household survey. Setting: Population sample of the Eastern Province of Saudi Arabia. Results: Hypertensive individuals had significantly higher mean levels of glucose, Tc, LDL-c, HDL-c, triglycerides and HBAIc, compared to normotensive individuals while there were no significant difference in the mean levels of Apo AI and Apo B. Within the same group there were variations in the levels of certain parameters between male and female. While the mean levels of haemoglobin, WBC and platelets were significantly higher in the hypertensive group compared to normotensive, there were no significant differences between these two groups in the levels of RBC, MCV, HCT, MCH and MCHC. However, the mean levels haemoglobin, RBC count and HCT were significantly higher in male compared to female within the same group with no significant difference in levels of WBC, MCV, MCH and MCHC. Furthermore, the mean concentration of platelets was significantly higher in females compared to male within the same group. Hypertensive individuals had significantly higher serum sodium, chloride and calcium levels but a significantly lower potassium level when compared to normotensive with no siginificant differences between male and female within the same group. Conclusion: The lipid and electrolyte profile of hypertensive individuals differ from that of normotensive individuals in this population. This study has contributed towards establishing the normal values for a number of parameters involved in the aetiology of cardiovascular diseases in the population of Eastern province. East African Medical Journal Vol. 83(1) 2006: 44-4

Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus Genotype 4 by 15 K cDNA microarray: Preliminary study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN response in Egyptian patients with HCV genotype-4

BACKGROUND: HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most common genotype of HCV and its response to treatment is still a controversy. METHODS: HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit. RESULTS: At the 48(th )week of treatment, 15 patients (68%) showed virological response. Whereas HCV-RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035). CONCLUSION: Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007) and the genetic distances between the quasispecies (p = 0.035). So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm this observation

HLA diversity in Saudi population : high frequency of homozygous HLA alleles and haplotypes

Human leukocyte antigens (HLA) diversity has a tremendous impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host–pathogen interactions. Here, we conducted a retrospective study of HLA class I and class II homozygosity at allelic and haplotype levels in unrelated individuals genotyped from 2012 to 2016 in a tertiary hospital in the capital of Saudi Arabia. Among 5,000 individuals, 2,773 individuals meet inclusion criteria and were retrospectively analyzed for HLA-A, -B, -C–DRB1, and -DQB1 homozygosity at allelic and haplotype levels. HLA molecular typing was performed using a commercial reverse sequencespecific oligonucleotide (rSSO) kit. We were able to identify 15 HLA-A, 20 HLA-B, 11 HLA-C, 13 HLA-DRB1, and five HLA-DQB1 homozygous alleles demonstrating a very low genetic diversity in the Saudi population. The highest homozygosity in HLA class I was found in locus C followed by A and B (20.3% > 16.1% > 15.5%; p < 0.001) where the most homozygote alleles were A*02 (9.2%), B*51 and B*50 (5.7% and 3.7%), and C*07, C*06, and C*15 (7.2%, 5.48%, and 3.3%) and in HLA class II, the highest homozygosity was found in locus DQB1 compared to DRB1 (31.71% > 19.2%; p < 0.001), with the most common homozygote alleles being DRB1*07 and DRB1*04 (5.33% and 4.2%) and DQB1*02, DQB1*06, and DQB1*03 (13.55%, 7.92%, and 7.64%). The frequency of finding an individual with one homozygote allele was (24.6%), two homozygote alleles (13.5%), three homozygote alleles (4.7%), four homozygote alleles (3.4%), and five alleles were (4.8%). The most frequent homozygote haplotypes are A*23~C*06~B*50~DRB1*07~DQB1*02 and A*02~C*06~B*50~DRB1*07~DQB1*02. This study shows low diversity of both class I and II alleles and haplotypes in the Saudi population, which would have a significant impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host–pathogen interactions.KFMChttps://www.frontiersin.org/journals/geneticsdm2022Medical Microbiolog

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

BACKGROUND: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. METHODS: The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. RESULTS: There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. CONCLUSIONS: Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets