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Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV "cure" is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.

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Aim: Assessing impact of lifestyle modification on Type 2 diabetes mellitus (T2DM) glycemic control and cognitive function. Subjects & methods: Prospective study was conducted on T2DM patients (92 patients as interventional group and 92 patients conventional therapy). Results: After 6 months, significant improvements of HbA1c, oxidant and antioxidant, lipid profile, and cognitive function among only the interventional group (p < 0.05). Using logistic analysis, conventional therapy, DM duration >10 years, lower education, HbA1c baseline >7 were significant predictive risks for uncontrolled DM (AOR 4.2, 2.9, 2.7 and 2.2, respectively). While, conventional therapy, baseline mild cognitive impairment (MCI) and females were significant risks for MCI (AOR 11.5, 10.8 and 4.8, respectively). Conclusion: Lifestyle modification is a very important for glycemic control and cognitive function.Clinical Trial Registration: NCT04891887 (ClinicalTrials.gov).

The study aimed at assessing the effect of lifestyle modification program on Type 2 diabetes mellitus (T2DM) patients. The program contents include maintaining healthy diet depending on glycemic index and CHO counting, adjusting cholesterol level, regular physical activity for at least 30 minutes; 3­5 days per week, weight loss and maintaining an appropriate weight, controlling the blood pressure, smoking cessation and practicing mental activity. After 6 months, there was a significant improvement in glycemic control, cognitive function, oxidant and antioxidant and lipid profile levels among patients participating in the program but not among those remained on the conventional therapy.

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Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

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AIM: To assess the role of serum biomarkers in early prediction of diabetic cardiomyopathy. MATERIALS AND METHODS: The participants were three groups of Type 2 diabetes mellitus (DM) patients having diastolic dysfunction (DM-DD), systolic dysfunction (DM-SD) and normal echocardiography (DM-N) with two control groups: non-DM diastolic dysfunction patients (DD) and healthy controls. AGEs, TNF-α, IL-6, IGFBP-7, creatinine and insulin were assessed. RESULTS: TNF-α, AGEs, creatinine and insulin panel had area under the curve (AUC) of 0.913 in distinguishing DM-DD from DM-N (78.7% sensitivity and 100% specificity). IL-6 and AGEs panel had AUC 0.795 for differentiating DM-SD from DM-DD (90.6% sensitivity). IL-6, TNF-α and AGEs panel had AUC 0.924 for differentiating diabetic cardiomyopathy from DM-N (85% sensitivity and specificity). CONCLUSION: A panel of AGEs, IL-6, TNF-α, insulin and creatinine might be used for early detection of DM-DD among T2DM patients.

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OBJECTIVES: We sought to assess the prevalence of hepatitis B virus (HBV) seroprotection among vaccinated children in the Assiut governorate, Egypt, and assess a booster dose immune memory response among non-seroprotected children. METHODS: Using a multistage cluster sample, 566 children were recruited from three clusters: one urban and two rural. Children were aged from nine months to 16 years old. All participants received the full three doses of the compulsory HBV vaccine during infancy. Serum hepatitis B surface antigen (HBsAg), total anti-hepatitis B core (anti-HBc) antibodies, and quantitative detection of anti-HBs were measured using enzyme-linked immunosorbent assay. Repeatedly positive samples for HBsAg/anti-HBc were submitted for quantitative HBV DNA detection using real-time polymerase chain reaction. Non-seroprotective participants (anti-HBs < 10 IU/L) were given a booster dose of HBV vaccine. Two weeks later, a blood sample was taken from each child to assess an anamnestic response. RESULTS: The seroprotection rate was 53.2%, and only two children had HBV breakthrough infection (0.4%) with positive serum anti-HBc and HBV DNA. Age was the only significant predictor for non-seroprotection with an adjusted odds ratio (OR) of 3.2, 9.4, and 9.9 among children aged 5-10, 11-15, and > 15 years, respectively, compared to younger children (p < 0.001). About 85% of non-seroprotected children developed an anamnestic response after receiving the booster dose, and 84.3% of responders had a good response (3 100 IU/L). Undetectable pre-booster titer was found to be the only risk factor for non-response to booster with OR = 3.2 (p < 0.010). About 95.7% of children who were not responding to booster dose developed immune response after receiving the three doses of HBV vaccine. CONCLUSIONS: Older age of children was the only significant predictor for HBV non-seroprotection. High anamnestic response rate signifies the presence of immune memory with long-term protection despite the waning of anti-HBs over time. However, some children with pre-booster undetectable anti-HBs titers may be unable to develop anamnestic response, and a second vaccination series might be necessary for HBV protection for these children.

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BACKGROUND: Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM: To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD: A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS: MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION: MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.

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OBJECTIVE: To evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children. SUBJECTS AND METHOD: A national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 µg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2-4 weeks) and long term (one year) anamnestic responses. RESULTS: Early anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1-9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15-16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively. CONCLUSION: Immunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children.

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OBJECTIVE: To evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination. SUBJECTS AND METHODS: After given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10 IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2(nd) vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10 IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2(nd) vaccination series. RESULTS: Protective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100 IU/L) and higher GMT (299.1 ± 3.6 IU/L) compared to those with undetectable 60% and 106.2 ± 12.9 IU/L respectively (P<0.05). No significant difference was detected as regards gender or residence, P>0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2(nd) vaccination series. CONCLUSION: A booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate.

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AIM: To assess the effectiveness of hepatitis B virus (HBV) vaccination program among fully vaccinated children. METHODS: A national community based cross-sectional study was carried out in 6 governorates representing Egypt. A total of 3600 children aged from 9 mo to 16 years who were fully vaccinated with HBV vaccine during infancy were recruited. Face to face interviews were carried out and sera were evaluated for hepatitis B surface antigen (HBsAg), anti-HBV core antibodies (total) and quantitative detection of hepatitis B surface antibody using enzyme linked immunoassays techniques. Samples positive to HBsAg/anti-HBV core antibodies were subjected to quantitative HBV-DNA detection by real time polymerase chain reaction with 3.8 IU/L detection limit. RESULTS: Sero-protection was detected among 2059 children (57.2%) with geometric mean titers 75.4 ± 3.6 IU/L compared to 3.1 ± 2.1 IU/L among non-seroprotected children. Multivariate logistic analysis revealed that older age and female gender were the significant predicting variables for having non sero-protective level, with adjusted odds ratio 3.3, 9.1 and 14.2 among children aged 5 to < 10, 10 to < 15 and ≥ 15 years respectively compared to those < 5 years and 1.1 among girls compared to boys with P < 0.01. HBsAg was positive in 0.11% and breakthrough infection was 0.36% and 0.39% depending on positivity of anti-HBc and DNA detection respectively. The prevalence of HBV infection was significantly higher among children aged ≥ 7 years (0.59%) compared to 0.07% among younger children with odds ratio equal to 8.4 (95%CI: 1.1-64.2) and P < 0.01.The prevalence was higher among girls (0.48%) than boys (0.29%) with P > 0.05. CONCLUSION: The Egyptian compulsory HBV vaccination program provides adequate protection. Occult HBV infection exists among apparently healthy vaccinated children. Adherence to infection control measures is mandatory.

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The long-term protective effect of hepatitis B virus (HBV) vaccine and the need for booster dose vaccination remain doubtful. The study aimed to estimate the sero-protection rate and evaluate immune response to a booster dose in children and adolescents with complete HBV vaccination during infancy. According to study design, 902 children were recruited from 2 cities and 3 villages in Dakahleya Governorate by a cross-sectional study; 475 boys and 423 girls with age range 9 months to 16 years. All received the three doses of the compulsory HBV vaccination during infancy. Serum samples were tested for hepatitis B surface antigen (HBsAg) Hepatitis B core antibodies (total) (HBcAb) & quantitative detection of antibodies to hepatitis B surface antigen (anti-HBs) using ELISA. Positive samples for HBsAg/HBcAb were subjected to quantitative HBVDNA detection by real time polymerase chain reaction (PCR). Those proved to have non-seroprotective antibodies (anti-HBs titres < 10 IU/L) were given a booster dose and a blood sample was drawn one month later for evaluation. Results of HBcAb and DNA revealed that 4 children had HBV breakthrough infection (4/902, 0.4% and only one out of them was positive for HBsAg. Out of the 898 children, 57.7% demonstrated sero-protective titers of anti HBs (> or = 10 IU/L) with geometric mean titres (GMTs) of 68.5 +/- 3.5 LU/L. The number of those with non-seroprotective titers was significantly lower among children < 5 years (11.1%) compared to those > or = 10 years (64.8%, P < 0.05), while no significant difference was noticed as regards the gender at any age group. Multivariate logistic analysis revealed that age was the only significant predictor variable for having non- seroprotective antibody level, with adjusted odds ratio (AOR) 4.2 & 14.1 among children aged 5-10 and older respectively compared to those aged < 5 years. About 92% of booster recipients developed anamnestic response. The GMTs of anti-HBs increased significantly. (189.4 +/- 12.3 IU/L), with no gender difference. Multivariate logistic analysis revealed that the pre-booster anti-HBs level < 3.3 IU/L was the only significant predictor variable for non responder to booster dose with AOR 6.6. It is concluded that in spite of the significant decline of level of antibodies over time yet, about half of the studied children have seroprotective level of antibodies after primary compulsory vaccination. Moreover, the developed anamnestic response among children with non-seroprotective level, confirms immunological memory that can outlast the presence of protective level of antibodies.

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