To evaluate whether hepatitis B virus (HBV) preS/S gene variability has any impact on serum hepatitis B surface antigen (HBsAg) levels and to analyze the replication capacity of naturally occurring preS/S variants, sera from 40 untreated patients with HBV-related chronic liver disease (hepatitis B e antigen [HBeAg]-positive, n 5 11; HBeAg-negative, n 5 29) were virologically characterized. Additionally, phenotypic analysis of three different preS/S variant isolates (carrying a 183-nucleotide deletion within the preS1 region, the deletion of preS2 start codon, and a stop signal at codon 182 within the S gene, respectively) was performed. HBV infecting 14 (35%) patients had single or multiple preS/S genomic mutations (i.e., preS1 and/or preS2 deletions, preS2 start codon mutations, C-terminally truncated and/or ''a'' determinant mutated S protein). Presence of preS/S variants negatively correlated with HBsAg titers (r 5 20.431; P 5 0.005) and its prevalence did not significantly differ between HBeAg-positive and HBeAg-negative patients. No correlation was found between HBsAg and HBV DNA levels in patients infected with preS/S mutants, whereas a significant correlation was found between HBsAg and viremia levels (r 5 0.607; P 5 0.001) in patients infected with wild-type HBV strains. HepG2 cells replicating the abovementioned three preS/S variants showed significant reduction of HBsAg secretion, retention of envelope proteins in the endoplasmic reticulum, less efficient virion secretion and nuclear accumulation of significantly higher amounts of covalently closed circular DNA compared with wild-type HBV replicating cells. Conclusion: In patients infected with preS/S variants, HBV DNA replication and HBsAg synthesis/secretion appear to be dissociated. Therefore, the use of HBsAg titer as diagnostic/prognostic tool has to take into account the frequent emergence of preS/S variants in chronic HBV infection. (HEPATOLOGY 2012;56:434-443) See Editorial on Page 411 H epatitis B virus (HBV) belongs to the Hepadnaviridae family, which comprises hepatotropic DNA viruses sharing with HBV most of the genetic structure and replicative characteristics. 1 HBV is one of the smallest viruses in nature and its genome presents a highly compact genetic organization. It consists of a partially double-stranded relaxed circular DNA of approximately 3,200 nucleotides in length and contains four partially overlapping open-reading frames: preS/S, pre-C-C, P, and X. The preS/S openreading frame encodes three different, structurally related envelope proteins termed the large (L), middle (M), and small (S) protein that are synthesized from alternative initiation codons. The three proteins share the same carboxy-terminus part but have different aminoterminal extensions. In particular, the S protein-corresponding to the HBV surface antigen (HBsAg)-consists of only 226 amino acids (aa), the M protein contains an extra N-terminal extension of 55 aa, and the L

BackgroundAsymmetric dimethylarginine (ADMA) plays a crucial role in endothelial function and maybe a link for the known interaction of periodontitis and coronary heart disease (CHD). In this pilot study, we compared the impact of gingival health, periodontitis (CP), CHD, or of both diseases (CP + CHD) on salivary and serum ADMA levels.MethodsThe clinical and periodontal characteristics, serum, and saliva samples were collected from 35 patients with CP, 33 patients with CHD, 35 patients with both CP + CHD, and 35 healthy subjects. Levels of ADMA and C‐reactive protein (CRP) were assessed with a commercially available kit.ResultsThe median (25% and 75% percentile) concentrations of salivary and serum ADMA were significantly higher in the CHD group [serum: 1.5 (1.2 to 1.8) μmol/L; salivary 1.3 (1 to 1.7) μmol/g protein, P < 0.01] and in the CP + CHD [serum: 1.8 (1.4 to 2.0) μmol/L; salivary 1.5 (1.2 to 1.7) μmol/g protein, P < 0.001] group compared to CP patients and controls. In univariate models, CP (P = 0.034), CHD (P < 0.001), and hs‐CRP (P < 0.001) were significantly associated with serum ADMA, whereas in a multivariate model, hs‐CRP remained a significant predictor of serum ADMA (P < 0.001). In a multivariate model, the significant predictors of salivary ADMA levels were hs‐CRP (P < 0.001) and education socioeconomic status (P = 0.042).ConclusionsPatients with CHD and CP + CHD presented higher levels of salivary and serum ADMA compared to healthy subjects and CP patients. hs‐CRP was a significant predictor of increased salivary and serum ADMA levels.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) interplay was investigated by examining liver and serum samples from 21 coinfected and 22 HBV-monoinfected patients with chronic liver disease. Different real-time PCR assays were applied to evaluate intrahepatic amounts of HBV DNA, covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA), pre-S/S RNAs, and HDV RNA. Besides HBV DNA and HDV RNA levels, HBsAg concentrations in the sera were also determined. HDV-coinfected cases showed significantly lower median levels of serum HBV DNA (؊5 log), intrahepatic relaxed-circular DNA (؊2 log), and cccDNA (؊2 log) than those of HBV-monoinfected cases. Interestingly, pgRNA and pre-S/S RNA amounts were significantly lower (both ؊1 log) in HDV-positive patients, whereas serum HBsAg concentrations were comparable between the two patient groups. Pre-S/S RNA and HBsAg amounts per cccDNA molecule were higher in HDV-positive patients (3-fold and 1 log, respectively), showing that HBV replication was reduced, whereas synthesis of envelope proteins was not specifically decreased. The ratios of cccDNA to intracellular total HBV DNA showed a larger proportion of cccDNA molecules in HDV-positive cases. For these patients, both intrahepatic and serum HDV RNA amounts were associated with cccDNA but not with HBsAg or HBV DNA levels. Finally, HBV genomes with large deletions in the basal core promoter/precore region were detected in 5/21 HDV-positive patients but in no HDV-negative patients and were associated with lower viremia levels. These findings provide significant information about the interference exerted by HDV on HBV replication and transcription activities in the human liver.Hepatitis delta virus (HDV) is a worldwide diffuse pathogen commonly associated with severe forms of liver disease (9,21,22,35). HDV can establish infection only in individuals with continuing hepatitis B virus (HBV) infection, since it requires obligatory helper functions provided by HBV for in vivo infection. In particular, HDV needs to borrow the envelope proteins produced by HBV, and consequently, the two viruses share the same outer coats, consisting of the HBV surface antigen (HBsAg) (21,35). In spite of this, HDV and HBV are completely different in terms of genome replication, with both showing several aspects that make their life cycles nearly unique among agents infecting animals. Very briefly, HDV is a small RNA virus with a single-stranded and circular genome of approximately 1,700 nucleotides (nt) that is replicated using a host RNA polymerase and contains a ribozyme able to selfcleave and self-ligate the circular HDV genome (30). In contrast, HBV is a closed, circular, partially double-stranded DNA virus of 3.2 kb containing four partially overlapping open reading frames that replicates via the formation of a circular covalently closed DNA (cccDNA) which serves as a template for the production of virus mRNAs, including an RNA pregenome that is reverse transcribed in the cytoplasm of hepatocytes for the synthesis of the DNA molecule...

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Age at HT presentation may influence autoimmune diseases clustering, favoring the association of specific NTADs in different ages of life. Moreover, the association between HT and NTADs increases with age and occurs most frequently in adults.

Our findings show that local and systemic arterial stiffness are increased in asymptomatic, normotensive HCh children, suggesting that HCh plays a key role in arterial mechanical impairment since the paediatric age.

Background and Objective Vitamin D has been considered to possess anti‐inflammatory and antimicrobial activity, which may be a link for the known interaction of periodontitis (CP) and coronary heart disease (CHD). This study investigated the association between serum vitamin D levels and periodontitis in patients with CP and with CHD. Furthermore, the objective was to determine whether periodontitis and CHD had an impact on serum vitamin D levels. Material and Methods Using a cross‐sectional design, a total of 46 patients with CP, 45 patients with CHD, 45 patients with both CP and CHD, and 43 healthy patients were enrolled in the present study. Results Patients in the CP (17.4 ± 5.2 ng/mL) and in the CP + CHD (16.5 ± 5.6 ng/mL) group presented a significantly lower mean serum level of 25(OH)vitamin D compared to patients in the CHD (24.6 ± 3.7 ng/mL) and healthy control groups (29.9 ± 5.4 ng/mL) (P < .001). 25(OH)vitamin D levels were positively correlated with the number of teeth and negatively with C‐reactive protein (CRP) and all periodontal parameters (P < .001). In all patients, there was a proportional increase of 25(OH)vitamin D levels with a progressive increase in number of teeth (P‐trend <.001) while there were a proportional decrease in 25(OH)vitamin D levels with a progressive increase in clinical attachment level (CAL, P‐trend = .001), probing depth (PD, P‐trend = .006), and bleeding sites (BOP, P‐trend <.001) levels. Conclusion Patients with CP and CP + CHD presented significantly lower serum levels of vitamin D compared to CHD and healthy controls. Moreover, the presence of CP negatively influenced serum vitamin D levels.

The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.