Hepatitis Monthly
Volume:19 Issue: 9, Sep 2019

A higher prevalence of hepatitis B virus (HBV) infection has been reported in persons with intellectual disability as well as the nurses working in closed institutions compared to the general population.

In the present study, the serological and molecular markers of HBV infection in individuals with intellectual disability of closed institutions were investigated.

Blood samples were derived from 400 persons with intellectual disability living in six institutions in Tehran and tested for HBsAg and HBcAb. Nested PCR, direct sequencing, and phylogenetic analysis were performed to determine the HBV genotypes and mutational patterns of HBsAg. Also, HBsAb was tested for HBV DNA positive cases.

Twenty-eight (7.0%) patients were positive for the HBsAg serological test. Furthermore, six HBV occult cases were identified. In total, out of 41 patients with HBV infection markers, 26 cases were positive for HBV DNA. Of these patients, 15 full-length HBsAg were successfully amplified and sequenced. All strains belonged to genotypeDand subtypes ayw2 and ayw3. These 15 isolated strains carried several immune escape mutants in the S genes. Surprisingly, mutations related to antiviral resistance were detected in the overlapped pol genes of strains isolated from naïve-treatment patients.

The observed frequency of HBV infection in individuals with intellectual disability was higher than the reported estimation of HBV infection in Iranian blood donors and the general population. All HBV isolates from these patients represented a homogenous genotype and  corresponded with other reported strains from Mediterranean countries. The high frequency of immune escape strains, despite vaccination and detection of identical mutational patterns in different genes, might indicate that persons with intellectual disability have shared vaccine-escape and drug-resistant HBV strains.

Nonalcoholic fatty liver disease (NAFLD) is the most abundant chronic liver disorder, because racial and ethnic differences may influence prevalence and severity of NAFLD.

This metabolomic study was conducted to identify the metabolic biomarkers and determine the mechanism of progress of NAFLD in Iranian patients.

Serum samples were collected from 75 participants (37 healthy controls and 38 patients with NAFLD) after an overnight fast. The metabolome of all samples were determined by nuclear magnetic resonance (NMR) and were compared by multivariate statistical analysis.

Totally, 19 metabolomic biomarkers were identified by NMR. Compared to healthy controls, NAFLD patients had increased serum concentrations of glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, deoxycholic acid, valine, isoleucine, succinic acid, isocitric acid, 2-ketoglutaric acid, trimethylamine, proline, hydroxyproline and tyrosine, while the concentrations of butyric acid, propionic acid, isovaleric acid, glutamine, glycine, and serine decreased.

A robust set of biomarkers for diagnosis of NAFLD was established. Serum metabolomics biomarkers revealed changes in some amino acids and their derivatives, bile acids, short chain fatty acids, and tricarboxylic acid cycle intermediates in subjects with NAFLD compared to healthy controls. These markers could be used as indicators regarding the efficacy of therapeutic interventions.

Nonalcoholic fatty liver disease (NAFLD) occur when the triglyceride accumulates in hepatic cells without history of alcohol consumption and strongly associated with insulin resistance, obesity, diabetes mellitus, hypertension, and dyslipidemia. Some studies have suggested the potential role of vitamin D in the pathogenesis of fatty liver disease.

Our aim was to determine the optimum vitamin D levels for NAFLD prevention.

In a cross-sectional study, 2160 referred to a university affiliated nutrition center randomly selected, their demographic, anthropometric, metabolic indices and vitamin D levels were obtained. Fatty liver assessed by fatty liver index (FLI) and confirmed by Fibroscan using controlled attenuation parameter (CAP). Based on the NAFLD score we divide them to two group and cut point for vitamin D calculated by ROC curve.

745 had different degrees of fatty liver (34.5%). Significant difference in stiffness of liver tissue was seen between of vitamin D categories (285.10  30.56, 251.82  42.63 and 201.02  36.08 for severe (< 12.5 nmol/L), moderate (25 > X > 12.5 nmol/L) and mild deficiency (50 > X > 25 nmol/L) respectively). In multivariate analysis age, fasting insulin, and status of vitamin D was the most significant variables in regard to NAFLD pathogenesis. Cut-off point for vitamin D calculated as 18 (nmol/L) for women and 21 (nmol/L) for men.

Results of our study, indicate significant association between vitamin D level and NAFLD score. So, the public’s recommendation to maintain a proper level of vitamin D may be preventative against non-alcoholic fatty liver disease.

Context:

It is reported that NTCP (sodium taurocholate cotransporting polypeptide) gene polymorphisms are associated with spon-taneous clearance of hepatitis B virus (HBV), but the results are contradictory. Therefore, the current meta-analysis aimed at system-atically clarifying the association between NTCP gene polymorphisms and spontaneous clearance of HBV in Asia.

Evidence Acquisition:

PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure and China Wanfang Data were searched systematically for articles published before 09 August 2019.

A total of nine case-control studies were finally included in the current meta-analysis. The pooled results indicated that the NTCP gene rs2296651 A allele is a protective factor for spontaneous clearance of HBV (GG vs. GA+AA: odds ratio (OR) = 0.73, 95%confidence interval (CI) = 0.58 - 0.93; GG vs. GA: OR = 0.74, 95%CI = 0.59 - 0.93; G vs. A allele: OR = 0.74, 95%CI = 0.58 - 0.94).

NTCP gene rs2296651 polymorphism is correlated with spontaneous clearance of HBV, while NTCP gene rs4646287 and rs7154439 variants are not associated with persistent HBV susceptibility.

Development of an effective prophylactic vaccine is the optimal long-term goal for the eventual control of HCV infection. An effective HCV vaccine should be able to elicit neutralizing antibodies (NAbs). Glycoprotein E2 of HCV is the major target for NAbs.

In this study, we designed and constructed a DNA vaccine (pcDNA-E2-NT(gp96)) encoding a fusion protein composed of HCV E2 ectodomain (genotype 1a) and N-terminal domain of gp96 as a biological adjuvant. Two possible forms of a fusion protein,  namely E2-NT(gp96) and NT(gp96)-E2, were made and subjected to in silico modeling and analysis. After the selection of the best form and confirmation its expression capacity in COS-7 cells, recombinant pcDNA-E2-NT(gp96) plasmid was generated by cloning of target genes into pcDNA3.1(+) plasmid. Constructed DNA vaccine immunogenicity was evaluated in BALB/c mice by measurement specific antibodies by ELISA and their neutralization capacity by neutralization assay.

In silico modeling and analysis showed that the E2-NT(gp96) structure was more valid than NT(gp96)-E2. Docking

revealed that the selected fusion protein had a high tendency for interaction with the main receptor (CD81) of HCV. GFP expression in COS-7 cells confirmed the E2-NT(gp96) expression capacity. Restriction enzyme digestion and sequencing results confirmed the integrity of the constructed plasmid. ELISA results showed that the pcDNA-E2-NT(gp96) induced high titers of specific antibodies in immunized mice. The sera of immunized mice cross-neutralized JFH1/HCVcc genotype 2a by 55% relative to pre-immune sera.

Total results showed that the generated DNA vaccine induced potent immune responses in immunized mice. Therefore, our findings are sufficiently encouraging to propose the pcDNA-E2-NT(gp96) as a promising vaccine candidate for HCV infection.