Potential Mutations Associated With Occult Hepatitis B Virus Status

Context:

Occult hepatitis B virus (HBV) status (OHBS) is simply defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum), in the absence of serum HBV surface antigen (HBsAg). Importance of OHBS is mostly clinical, related to its possible role in spreading through blood transfusion and liver transplantation; causing classic forms of HBV. Mechanisms underlying this entity are poorly defined. Several possibilities have been suggested, with major classification into two groups: defective host immune response and viral replication activity through mutations of HBV DNA sequence. Mutations are extensively investigated in all four overlapping open reading frames (ORFs) of HBV genome, to define their possible role in the pathogenesis of OHBS. Some of these mutations like S-escape mutants could not be detected by the routine available assays, making them difficult to diagnosis. Therefore, trying to detect this covert condition could be more helpful for defining better preventive and therapeutic strategies.

Evidence Acquisition:

In the present study we provided an in-depth review of the most important new data available on different mutations in HBV genome of patients with OHBS, which may play a role in the pathogenesis of OHBS. The data were collected through reviewing the full-text articles, identified by the PubMed search, using the following keywords and their different combinations: occult hepatitis B, HBV genome, "a" determinant, HBV open reading frames, S mutations, X mutations, P mutations and C mutations.

Results:

Variants within the major hydrophilic region (MHR) of the HBsAg, deletions in the pre-S1region, codon stop in the S open reading frames (ORF), sporadic non common mutations, some mutations affecting the posttranslational production of HBV proteins in the S ORF like deletion mutations, mutations in start codon and nucleotide changes in the X ORF, deletion and point mutations in P ORF and sometimes, nucleotide substitution in the C ORF are among the assumed mutations detected to have a role in OHBS appearance.

Conclusions:

Studies mostly lacked a control group and the whole-length HBV sequencing was scant with conflicting results, suggesting that OHBS is often a result of multiple mechanisms. Additional studies on full-length HBV genomes from occult and non-occult HBV cases may shed more light on the interplay between different mechanisms involved in the pathogenesis of OHBS.     

Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials

ObjectiveSeveral studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness and wave reflections as measured by pulse wave velocity (PWV) and augmentation index (AIx), respectively. We conducted a meta-analysis to investigate this effect in comparison to placebo and to other antihypertensive agents. Additionally, we investigated this effect when ACEIs are combined with other antihypertensive agents and in comparison to a combination of antihypertensive agents.MethodsMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to May 2011 on randomised controlled trials (RCTs) which assessed the effect of ACEIs on arterial stiffness vs. placebo or no treatment and ACEIs vs. angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), β-blockers and diuretics. RCTs which assessed the effect of ACEIs combined with other antihypertensives or compared ACEIs with a combination of antihypertensives were also sought. Data from included RCTs were pooled with use of fixed and random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I² statistic.ResultsIn 5 trials including 469 patients, treatment with ACEIs (n = 227) vs. placebo (n = 216) significantly reduced PWV (pooled mean change difference ?1.69, 95% C.I. ?2.05, ?1.33, p < 0.00001 with insignificant heterogeneity). In 9 trials which included 378 patients, treatment with ACEIs (n = 178) insignificantly reduced PWV when compared with other antihypertensives (ARBs, CCBs, β-blockers, diuretics and a combination of ACEI and ARB) (n = 220) (pooled mean change difference ?0.19, 95% C.I. ?0.59, 0.21, p = 0.36, I² = 0%). ACEI effect on AIx in comparison to placebo was assessed in 7 trials. Treatment with ACEIs significantly reduced AIx (pooled mean change difference ?3.79, 95% C.I. ?5.96, ?1.63, p = 0.0006) with significant heterogeneity. In 7 trials, treatment with ACEIs significantly reduced AIx when compared with other antihypertensives (pooled mean change difference ?1.84, 95% C.I. ?3, ?0.68, p = 0.002, I² = 32%, p for heterogeneity = 0.11). However, this effect was only significant when compared with β-blockers (pooled mean change difference ?1.6, 95% C.I. ?2.84, ?0.36, p = 0.01). Mean BP differences between baseline and end of treatment did not predict the treatment (ACEI) induced changes in PWV.ConclusionsACEIs reduce PWV and AIx which are markers of arterial stiffness and wave reflections in patients with different pathological conditions. However, due to the lack of high quality and properly powered RCTs, it is not clear whether ACEIs are superior to other antihypertensive agents in their effect on arterial stiffness. The ability of ACEIs to reduce arterial stiffness (PWV) seems to be independent of its ability to reduce BP.     

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.     

Knowledge and attitudes of physicians in private practice towards HIV/AIDS in Mashhad, Iran

Being responsible for providing care for HIV/AIDS in a society, physicians should be knowledgeable and have favourable attitudes. We designed a cross-sectional study to assess knowledge and attitudes towards HIV/AIDS of private practicing physicians in Mashhad, Iran. A total of 346 general practitioners and specialists completed anonymous self-administered questionnaires with response rate of 91.1%. For knowledge questions, the mean proportion of correct responses was 53.5% (±13.2). Misconceptions about HIV transmission were the main areas of insufficient knowledge. Surprisingly only 20% knew how to manage a patient who had experienced sexual contact with an HIV-positive partner. While 84% disagreed that 'HIV-infected individuals deserved to catch infection' owing to high-risk behaviours, 38% sympathized less with people who were infected via extramarital sex. It seems that knowledge and attitudes towards HIV/AIDS among the studied physicians is not favourable and is an area that requires attention to enable effective management of the disease in Iran.